A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review

A Pharmacist Perspective on Optimizing... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/13-748" }, "headline": "A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review", "datePublished": "2024-07-05T09:46:20", "dateModified": "2024-07-05T09:46:20", "author": [ { "@type": "Person", "name": "Priya Manirajan" }, { "@type": "Person", "name": "Palanisamy Sivanandy" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Multimorbidity and the associated consumption of multiple medications are common among the older population, posing a significant health concern. This leads to an increased incidence of side effects, adverse drug reactions, and higher healthcare costs for the individual, their family, and the country’s overall healthcare expenditure. Older adults experience complications due to the natural aging process and polypharmacy. The pharmacokinetic and pharmacodynamic variables of medications play a crucial role in their recovery and overall health. While many studies have highlighted the rising incidence of multimorbidity among older adults, they often overlook the importance of optimizing medication therapy to reduce complications, side effects, adverse drug reactions, falls, and improve medication adherence. This narrative review focuses on the impact of polypharmacy on older adults, age-related pharmacokinetic changes, pharmacodynamics in this population, and various methods to optimize pharmacotherapy. The findings of this review aim to provide healthcare providers with a better understanding of how to optimize pharmacotherapies and reduce drug-related complications in older adults." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-748", "name": "A Pharmacist Perspective on Optimizing Pharmacotherapy among Older..." } } ] } Home Browse A Pharmacist Perspective on Optimizing Pharmacotherapy among Older... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Manirajan P and Sivanandy P. A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.12688/f1000research.152996.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Review A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] Priya Manirajan 1 , Palanisamy Sivanandy https://orcid.org/0000-0002-9183-5091 1 Priya Manirajan 1 , Palanisamy Sivanandy https://orcid.org/0000-0002-9183-5091 1 PUBLISHED 05 Jul 2024 Author details Author details 1 Department of Pharmacy Practice, School of Pharmacy, IMU University, Kuala Lumpur, 57000, Malaysia Priya Manirajan Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation Palanisamy Sivanandy Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Resources, Software, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Health Services gateway. Abstract Multimorbidity and the associated consumption of multiple medications are common among the older population, posing a significant health concern. This leads to an increased incidence of side effects, adverse drug reactions, and higher healthcare costs for the individual, their family, and the country’s overall healthcare expenditure. Older adults experience complications due to the natural aging process and polypharmacy. The pharmacokinetic and pharmacodynamic variables of medications play a crucial role in their recovery and overall health. While many studies have highlighted the rising incidence of multimorbidity among older adults, they often overlook the importance of optimizing medication therapy to reduce complications, side effects, adverse drug reactions, falls, and improve medication adherence. This narrative review focuses on the impact of polypharmacy on older adults, age-related pharmacokinetic changes, pharmacodynamics in this population, and various methods to optimize pharmacotherapy. The findings of this review aim to provide healthcare providers with a better understanding of how to optimize pharmacotherapies and reduce drug-related complications in older adults. READ ALL READ LESS Keywords Complications, medications, older adults, optimization, polypharmacy Corresponding Author(s) Palanisamy Sivanandy ( [email protected] ) Close Corresponding author: Palanisamy Sivanandy Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Manirajan P and Sivanandy P. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Manirajan P and Sivanandy P. A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.12688/f1000research.152996.1 ) First published: 05 Jul 2024, 13 :748 ( https://doi.org/10.12688/f1000research.152996.1 ) Latest published: 05 Jul 2024, 13 :748 ( https://doi.org/10.12688/f1000research.152996.1 ) Introduction Older adults, also known as seniors or elders, are individuals who are 65 years and older. The advancements in healthcare globally have helped increase longevity, resulting in a growing aging population worldwide. It is estimated that the percentage of individuals aged 65 and older will increase from 10% in 2022 to 16% in 2050. 1 – 3 Additionally, the report predicts that by 2050, the ratio of the elderly population to children under the age of five will be 2:1. 3 This increase in the elderly population is primarily attributed to lower mortality and higher survival rates. Figure 1 and Figure 2 illustrate the top 50 countries with the highest percentage of older population, 2 as well as the distribution of the world’s oldest populations by country or territory in 2022 and 2050 3 respectively. Figure 1. Top 50 countries with the largest older population percentage. Figure 2. Country or territory-wise the world's oldest populations share by 2022 and 2050. One of the main health concerns among older adults is the presence of multimorbidity. Multimorbidity is defined as the presence of two or more non-communicable diseases, for example, hypertension, 4 diabetes, 5 , 6 depression, and so on. 7 A recent study reported a global prevalence of multimorbidity of 37.2%. 8 The same study pointed out that 51% of adults aged 60 years and above have multimorbidity. This finding is similar to an Indian study, which reported an increasing prevalence of multimorbidity from 48.31% in those aged 45 years and above to 73.86% in those aged above 75 years. 9 Similarly, a study from Malaysia reported that 40.6% of the country’s older adults have multimorbidity. 10 Multimorbidity is common among older adults due to declining physiological function and the presence of shared risk factors such as smoking, a sedentary lifestyle, and an unhealthy diet which lead to the onset and progression of chronic diseases. Pharmacotherapy treatment is the mainstay for many non-communicable diseases. The increasing prevalence of multimorbidity leads to older adults being prescribed a higher number of medications, resulting in polypharmacy and hyperpolypharmacy. Polypharmacy is when a patient uses five or more medications, while hyperpolypharmacy is when they use ten or more medications. 11 – 13 The reported prevalence of polypharmacy in the literature varies widely, ranging from 2.6% to 86.6%. 14 , 15 Despite the benefits of managing multimorbidity, increased medication consumption can have unwanted effects on older adults. This article aims to guide healthcare providers (HCPs) in optimizing pharmacotherapy for older adults taking into consideration the unique physiological changes and challenges that come with aging. Impact of polypharmacy on older adults Polypharmacy significantly increases the risk of medication-related problems among older adults. These problems include drug interactions, inappropriate prescribing, prescribing cascade, medication non-adherence, and more. 16 , 17 Drug interactions are more common among older adults with polypharmacy and can manifest in various ways, such as drug-drug interactions, drug-disease interactions, or drug-food interactions. Drug-drug interactions typically decrease the effectiveness of medication by either inhibiting drug metabolism or increasing clearance. For instance, an elderly patient with hypertension who takes non-steroidal anti-inflammatories (NSAIDs) for knee pain may experience a drug interaction with an ACE inhibitor, leading to elevated serum potassium levels and reduced kidney function. In the case of drug-disease interactions, chronic NSAID use in a heart failure patient can exacerbate their condition. Additionally, drug-food interactions can impact the outcome of pharmacotherapy by altering the drug’s pharmacokinetics. One common example is warfarin, a vitamin K antagonist, taken with green leafy vegetables high in vitamin K content, which can affect the anticoagulation stability of warfarin. Inappropriate prescribing is common among older adults ranging from 45.3% to 51%. 18 One of the leading causes of polypharmacy besides comorbidities is overprescribing. Overprescribing refers to prescribing medications more than necessary for patients. Overprescribing tends to increase with age and higher prevalence was reported among older people near the end of life in some studies up to 76%. 19 A study conducted in the United States, reported that antidepressants, thyroid hormones, proton pump inhibitors, H 2 receptor blockers, and analgesics were commonly overprescribed medications among older adults. 20 In addition to overprescribing, underprescribing can also be an issue. Underprescribing or underprescription is defined as the failure to prescribe a drug that is indicated for the management of a condition or illness, despite the absence of a valid basis for doing so. 21 Underprescribing can also occur to avoid polypharmacy among older adults. A study reported that the prevalence of underprescribing ranges from 22% to 70% among the older population. 22 Numerous factors, such as multimorbidity, polypharmacy, dementia, frailty, risk of adverse pharmacological events, lack of specific clinical trials for older patients, and economic concerns, are linked to under-prescription. 23 , 24 Underprescribing leads to negative outcomes such as an increased risk of cardiovascular events, deteriorating disability, hospitalisation, and mortality. 25 , 26 Medication adherence refers to the extent to which a person follows a doctor’s instructions for taking medications. 27 This includes taking the right medication, at the right dose, at the right frequency, and at the right time. Medication adherence can be challenging for older adults with multimorbidity and polypharmacy thus, leading to non-adherence. There are several risk factors identified for non-adherence among older adults with multimorbidity and polypharmacy. Cognitive decline is observed among the aging population which leads to unintentional omission of medications. 28 , 29 Moreover, the complexity of pharmacotherapy prescribed for such patients does not help with adherence levels either. 30 , 31 Other reported factors include sex, medication cost, lack of social support, health literacy, and self-administration of drugs. 32 – 34 Adverse drug reactions (ADRs) are common and widely reported among older adults with polypharmacy and multimorbidity. 35 , 36 This is due to age-related changes in pharmacokinetics and pharmacodynamics, such as decreased hepatic and renal function, longer elimination half-lives, and higher sensitivity to medications. Older adults are more susceptible to ADRs compared to younger adults. ADRs often lead to increased hospital admissions with stays of up to 6 days and a mortality rate of 0.34%. 37 Medications commonly associated with ADRs include analgesics, antithrombotics, proton pump inhibitors, antihypertensives, antidepressants, antipsychotics, and bisphosphonates. 38 – 40 Drug-drug interactions have also been identified as a significant factor in ADRs development. Specific drugs that are known to cause ADRs due to interactions include warfarin, aspirin, heparin, and other antithrombotic agents. 41 , 42 These drugs can interact with proton pump inhibitors, antidepressants, and antiplatelets leading to gastrointestinal or cerebral haemorrhagic events. Multimorbidity and polypharmacy increase the likelihood of prescribing cascade events in older adults. A prescribing cascade is when an adverse drug event (ADE) is mistaken for a new medical condition, leading to the unnecessary addition of another medication. 43 For example, a diuretic may be prescribed to reduce edema caused by calcium channel blockers used for hypertension. Another common prescribing cascade involves prescribing an antiparkinsonian agent to address extrapyramidal symptoms caused by antipsychotic agents. These cascades not only worsen the effects of an unrecognized ADR but also contribute to the development of chronic polypharmacy. 11 Age-related pharmacokinetic changes When prescribing pharmacological agents to older adults, it is crucial to consider pharmacokinetic changes such as absorption, distribution, metabolism, and elimination. The pharmacokinetics of medications can be affected by age-related pharmacologic changes as well as sex-related changes and multimorbidity, which are more common in the elderly. Additionally, pharmacokinetic changes in older adults can be affected by geriatric syndromes as well. 44 Ageing affects all organ systems including the gastrointestinal system which is responsible for the absorption of medicated oral preparations. The gastrointestinal system plays a crucial role in motility, enzyme and hormone secretion, and the digestion of food. One common complaint among older adults is xerostomia or dry mouth. Xerostomia can be caused by systemic diseases like Sjogren’s syndrome, pharmacological agents such as atropine, and radiation therapy that damages the salivary glands. Salivary gland hypofunction may impair drug absorption through the oral mucosa, such as sublingual glyceryl trinitrate, reducing clinical efficacy. 45 The walls of the small and large intestines reduce in size among older adults leading to a reduced surface area, and impaired absorption. 46 Additionally, an aging-related decrease in hydrochloric acid production can lead to impaired absorption of certain drugs such as aspirin, and early release of drugs from enteric-coated oral formulations. 47 The passage of medications from the stomach into the small intestine can be prolonged by age-related delay in gastrointestinal motility or the consumption of anticholinergic medications. 48 Delayed motility can impair absorption, onset of action, peak drug concentration, and clinical effects of medications like paracetamol, which is absorbed in the upper small intestine. As a person ages, body fat increases while total body water, blood, and plasma volume decline. These changes result in an increased volume of distribution and half-life of lipophilic drugs like diazepam. Therefore, when the same medication dose is prescribed to older adults and young people, it can lead to higher levels of free drugs and greater effectiveness in older adults, potentially causing toxicity. Additionally, it can decrease the distribution of hydrophilic drugs like digoxin and lithium. In addition to changes in plasma volume, older adults also experience decreases in plasma proteins such as albumin and lean tissue as they age. Drugs with high protein binding, like warfarin and phenytoin, may become unbound when albumin levels are reduced, especially during illness, leading to an increased risk of toxicity. 49 On the other hand, α-1-acid glycoprotein increases with age, resulting in decreased free concentrations of basic drugs such as amoxicillin, potentially leading to inadequate dosing. The impact of first-pass metabolism by the liver decreases with age. The decline in hepatic metabolism is characterized by a decrease in liver mass, blood flow, and hepatic enzymes such as cytochrome P-450, flavine monooxygenases, and UDP glucuronosyl transferases. 49 A study in Japan stated that hepatic unbound clearance fell by 32% at age 80 and 40% at age 90 compared to age 40, implying a 0.80% annual decline with age. 50 Hence, older adults may have higher circulating drug concentrations for a given oral dose. Drugs such as nitrate, propranolol, phenobarbital, and nifedipine are some examples of medications with an increased risk of toxic effects due to a decline in physiological function. The hepatic metabolism of drugs can also be impacted by smoking, reduced hepatic blood flow in heart failure patients, and the use of medications that activate or inhibit the cytochrome P-450 metabolic enzymes. The aging process not only affects the absorption, distribution, and metabolism of drugs but also alters the renal elimination of drugs. The size of the kidney decreases by 20-30% between the age of 30 to 80 years. 49 Besides structural changes, the glomerular filtration rate (GFR), renal plasma flow, and tubular function also decrease with age. 51 More often, the serum creatinine level is maintained within the normal range despite reduced GFR due to less muscle mass. 52 Therefore, drug doses should be tailored according to the measured renal clearance of the patient using equations such as CKD Epidemiology Collaboration, Berlin Initiative Study, and Full Age Spectrum which are more accurate than Cockcroft–Gault. 53 Drugs that rely heavily on renal elimination such as sildenafil, clozapine, amoxicillin, and others require a reduction in dose and/or frequency to avoid toxic plasma concentrations of drugs. 54 Pharmacodynamics in older adults Pharmacodynamics as opposed to pharmacokinetics examines the drug’s action on the body. It can be affected by receptor binding and sensitivity, post-receptor effects, chemical interactions, and physiological changes due to disease, genetic mutations, aging, or other drugs. 55 Therefore, older adults may have a different physiological response to the same drug dosing compared to younger patients. Increasing age can increase sensitivity to most drugs such as digoxin, warfarin, opioids, antipsychotics, and diuretics. However, β-adrenoceptor responsiveness decreases with age due to decreased activation of adenylyl cyclase and reduced production of cAMP. 56 This means that β-blocker doses may need to be increased to achieve an adequate response. In addition, older adults also have increased sensitivity to anticholinergic drugs. The side effects of these drugs include dry mouth, constipation, delirium, blurred vision, and urinary retention. Commonly consumed medications with anticholinergic effects include antipsychotics, tricyclic antidepressants, and sedative antihistamines. Taking multiple medications with anticholinergic effects can result in an anticholinergic burden, which, when combined with aging, may lead to cognitive decline and a loss of functional capacity. 57 Furthermore, older adults with a moderate to high anticholinergic burden are at an increased risk of falls. 58 Therefore, it is highly encouraged to regularly review medications and consider deprescribing drugs with anticholinergic effects. Optimizing pharmacotherapy in older adults Despite the challenges associated with pharmacotherapy management in older adults, there are practical ways to resolve these issues. The following steps can be taken to overcome pharmacotherapy challenges in older adults: Medication review A medication review is a routine practice conducted in healthcare settings by doctors, pharmacists, and nurses. 59 This process can be valuable in identifying medications with anticholinergic burden, potentially inappropriate medications (PIMs), and prescribing cascade events that are commonly observed in older adults. When performed correctly and regularly, medication reviews can help detect many drug-related issues early on, such as side effects, adverse effects, interactions, or missed doses. 60 The primary goal of a medication review is to ensure that medications are functioning as intended and addressing the patient’s health concerns. Additionally, it can simplify medication regimens and promote adherence in older adults with polypharmacy. The medication review process can take place in various settings, including nursing homes, hospitals, primary care facilities, community pharmacies, and during home visits. From a patient’s perspective, a medication review provides an opportunity for older adults and their caregivers to discuss any concerns or questions they have about their medications with a HCP. This open communication can lead to better medication management and improved overall health. In recent years, the National Health Service in England has introduced a comprehensive medication review called Structured Medication Review (SMR). SMRs are evidence-based and thorough reviews of a patient’s medication, taking into account all aspects of their health. The SMRs are intended for patients with hyperpolypharmacy, severe frailty, and potentially addictive pain management medications, which are commonly found in older adults. 61 These SMRs can be implemented by healthcare facilities in different countries to improve the optimization of prescribed medications. By addressing medication errors, improving adherence, and ensuring optimal medication use, medication reviews can significantly improve health outcomes for older adults. This can lead to fewer hospitalisations, improved quality of life, and a reduction in healthcare costs. In addition to this, medication reviews can also help prevent falls and related injuries. 62 Figure 3 describes the optimization of pharmacotherapy in older adults. Figure 3. Optimization of pharmacotherapy in older adults. Deprescribing Deprescribing has recently gained popularity due to an aging society with an increasing number of individuals living with various chronic diseases. Deprescribing is defined as the process of tapering, withdrawing, discontinuing, or stopping medications to reduce potentially problematic polypharmacy, ADE, and inappropriate or ineffective medicine use. 63 Deprescribing is a practical approach to reducing ADRs, improving adherence, reducing pill burden, lowering fall risk, and enhancing quality of life. 64 , 65 A multicenter controlled trial conducted in Australia found that a deprescribing strategy significantly decreased the number of medications prescribed to older adults with polypharmacy, with no adverse events reported. 66 The most frequently deprescribed medication classes were supplements, gastric acid suppressants, statins, oral hypoglycemics, and diuretics. Deprescribing medications like diuretics can potentially prevent the prescribing cascade. Furthermore, deprescribing reduces exposure to high-risk anticholinergics, thus decreasing the anticholinergic burden in older adults and avoiding unwanted side effects such as dry mouth, constipation, urinary retention, cognitive impairment, and dementia. 67 Similarly, a randomized controlled trial in Ireland reported that deprescribing significantly reduced polypharmacy and medication costs in frail older adults. 68 Deprescribing can be accomplished in five simple steps 69 , 70 ; Step 1: Obtain a comprehensive medication history and assess adherence. Step 2: Identify any PIMs. Step 3: Decide if the dosage can be lowered or if the medication can be discontinued. Step 4: Develop a plan for tapering and withdrawing the medication. Step 5: Monitor the outcomes, including improvements in clinical parameters, and ADRs. There are numerous tools available to assist clinicians in deprescribing medication. A popular tool is the STOPP/START (Screening Tool of Older Persons’ Prescriptions/Screening Tool to Alert to Right Treatment) criteria. It is a physiological systems-based explicit set of criteria that aims to define clinically important prescribing problems related to PIMs and potential prescribing omissions. 71 Other useful tools that can be used in clinical settings include the Medication Appropriateness Index, Good Palliative-Geriatric Practice, Current medicines, Elevated risk, Assess, Sort, Eliminate algorithm, and Beers Criteria. 72 Identifying prescribing cascades in clinical practice can be challenging for clinicians. Therefore, the ThinkCascades tool was recently developed through a modified Delphi process with an international multidisciplinary expert panel to identify clinically important prescribing cascades affecting older adults, which helps prevent and manage polypharmacy. 73 Individualized treatment approach Due to the complex interplay of age-related physiological changes, multimorbidity, and declined cognitive function, individualized treatment approaches are crucial for older adults. A one-size-fits-all approach is not sufficient, as health heterogeneity increases to varying degrees with age. 74 , 75 Therefore, prescribers need to consider older adults’ comorbidities, and physiological functions such as renal function, cognitive function, functional status, and life expectancy before prescribing any medications. When it comes to prescribing medications for older adults, a key principle that HCPs need to remember is ‘start low, go slow’. Initiating medications with low doses and titrating up the dosage until a desirable treatment outcome has been achieved including the absence of adverse effects, is important. Tools like STOPP/START and Beers Criteria can be used when prescribing medications for older adults. Prescribing combination medications such as felodipine and enalapril in a single formulation, can reduce polypharmacy and improve adherence among older adults. Individualized treatment recognises the unique life experiences and challenges older adults face, such as loss, retirement, or changes in living situations. This fosters a more empathetic and relatable therapeutic environment. For instance, frail older adults may have difficulties in managing complex insulin therapy, so simplifying or de-escalating the treatment would benefit them greatly. 76 Treatment plans can be adjusted as needed to accommodate changes in health or preferences, ensuring the approach remains safe and effective over time. Overall, individualized treatment empowers older adults to take charge of their well-being and achieve a higher quality of life. Development of geriatric specific guideline The development of geriatric-specific guidelines is crucial for improving the care of older adults. The need for population-specific guidelines arises from the unique challenges faced by older adults. These challenges include physiological changes, polypharmacy, and cognitive decline. General clinical guidelines available in most healthcare facilities might not address these complexities, potentially leading to poorer health outcomes. One of the major challenges in developing guidelines is determining best practices or recommendations based on available evidence. This is because the majority of clinical trials may not include older adults in the study, so the outcomes may not be generalised for this population. Clinical trials need to consider the inclusion of older adults as the population is expected to grow in the future. Pharmacy-related geriatric guidelines should be developed in hospitals, primary care clinics, nursing homes, and community pharmacies to provide optimal prescribing. Some of the pharmacy-related geriatric guidelines include the Pharmacist’s Comprehensive Geriatric Assessment in France, the Medication Therapy Adherence Clinic for Geriatrics and the Geriatric Pharmacy Pocket Book in Malaysia. 77 These guidelines not only help clinical pharmacists but also other HCPs in making treatment decision. Patient education Patient education plays a critical role in optimizing pharmacotherapy for older adults. Understanding their medications helps older adults take them correctly, at the right times, and for the intended duration. This reduces the risk of missed doses or misuse, leading to better treatment outcomes. Educated patients are more likely to identify potential problems like drug interactions or side effects and medications that potentially increase the risk of falls. 78 They can then communicate these concerns to their HCPs, preventing complications. Knowledge about medications empowers older adults to manage their conditions more effectively. They can recognise signs of improvement or worsening health, allowing for timely adjustments to their treatment plan. Understanding their medications fosters a sense of control and autonomy in older adults. This can lead to greater satisfaction with their healthcare and a more active role in their treatment decisions. There are some practical ways to provide patient education in daily practice. Firstly, tailored communications are key. Older adults typically experience sensory loss, memory decline, and slower processing of information. Therefore, it is important to use clear, concise language and address individual needs and learning styles. Speak slowly, clearly, and loudly enough for them to understand the information being conveyed. Visual aids or written information can also be helpful as a reference for older adults. 79 Emphasize potential side effects of prescribed medications, proper medication administration, and when to seek medical attention. It is crucial to create a comfortable environment where older adults can ask questions and express concerns without fear of judgment. Patient education should also be extended to family members or caregivers who assist with medication management. In addition to verbal communication, patient education handouts, either physical or electronic, can be provided to patients and their caregivers for Ref. 40 . This will undoubtedly improve the care provided to older adults. Collaborate with a multidisciplinary team A multidisciplinary approach is beneficial for optimizing pharmacotherapy. The team can include geriatricians, physicians, pharmacists, nurses, dieticians, physiotherapists, and other specialists. By combining expertise from various disciplines, the team can gain a holistic understanding of the patient’s health, including medical conditions, cognitive function, and social circumstances. This allows for a more individualized medication plan. Collaboration among team members helps identify and prevent potential medication errors, minimizing the risk of ADRs. A study conducted in the United States reported that a multidisciplinary team consisting of clinical pharmacists has led to significantly more deprescribing of PIMs. 81 Through education and support from various HCPs, patients are more likely to understand and adhere to their medication regimens. Open communication within the team ensures everyone involved is on the same page about the patient’s treatment plan and avoids overlapping medical records and prescriptions. The collaborative effort exhibited by the multidisciplinary team can optimize medication use to improve the older adult’s health, quality of life, and functional ability. Promote patient autonomy & shared decision-making Prescribing medications for older adults involves a unique set of ethical considerations, especially regarding patient autonomy and shared decision-making. Older adults cherish their independence and their ability to take charge of their healthcare. HCPs must respect this autonomy by offering clear information about medications, possible side effects, and treatment objectives in a way that is easy to comprehend, taking into account any cognitive limitations. Patients should feel empowered to ask questions and voice any concerns they may have. Ultimately, the decision to accept or decline medication lies with the patient, even if it contradicts the doctor’s advice. However, patient autonomy can be compromised by a few factors. Older adults with cognitive impairment have difficulties comprehending complex medication information and making informed decisions. In addition to cognitive impairment, polypharmacy dampers autonomy by creating adherence issues. When autonomy is challenged, shared decision-making becomes crucial. This involves including the patient in discussions but may also involve incorporating input from trusted family members or caregivers. Family members can provide valuable insights into the patient’s medical history, daily functioning, and preferences. The patient’s level of understanding and decision-making ability should always be prioritised. If the patient lacks capacity, a healthcare proxy or legal guardian may need to be involved. Clear communication with both the patient and family is essential to ensure everyone understands the treatment plan and its potential benefits and risks. Overall, the goal is to find a balance between respecting patient autonomy and ensuring their well-being. This can involve a flexible approach that adapts to the individual needs and circumstances of each older adult. Conclusion The older adult population is heterogeneous, with differences in physiology due to aging altering pharmacokinetics and pharmacodynamics, functional disabilities, cognitive impairment, and multimorbidity to varying degrees. This leads to an increased incidence of polypharmacy and ADRs. Therefore, optimizing pharmacotherapy for the growing older adult population will greatly benefit their health. Data availability No data are associated with this article. References 1. United Nations Population Division: World Population Prospects 2022: Summary of Results. New York: United Nations Population Division; 2019. [cited 2024 Mar 03]. Reference Source 2. Felix Richter: The world’s oldest populations.Updated Feb 20, 2024. [cited 2024 Mar 03]. Reference Source 3. The top 50 countries with the largest percentage of population aged 65 and up. MADISON Trust Company; [cited 2024 Mar 08]. Reference Source 4. Kumaran ASG, Yohannan JK, Jijie J, et al. : Development and implementation of patient information leaflet on hypertension and to assess its effectiveness. Int J Pharm Tech Res. 2009; 1 : 712–719. 5. Chinnappan S, Sivanandy P, Sagaran R, et al. : Assessment of knowledge of diabetes mellitus in the urban areas of Klang district, Malaysia. Pharmacy. 2017; 5 : 11. PubMed Abstract | Publisher Full Text | Free Full Text 6. Selvakumar D, Sivanandy P, Ingle PV, et al. : Relationship between treatment burden, health literacy, and medication adherence in older adults coping with multiple chronic conditions. Medicina. 2023; 59 : 1401. PubMed Abstract | Publisher Full Text | Free Full Text 7. Skou ST, Mair FS, Fortin M, et al. : Multimorbidity. Nat Rev Dis Primers. 2022; 8 : 48. PubMed Abstract | Publisher Full Text | Free Full Text 8. Chowdhury SR, Das DC, Sunna TC, et al. : Global and regional prevalence of multimorbidity in the adult population in community settings: a systematic review and meta-analysis. EClinicalMedicine. 2023; 57 : 101860. PubMed Abstract | Publisher Full Text | Free Full Text 9. Khan MR, Malik MA, Akhtar SN, et al. : Multimorbidity and its associated risk factors among older adults in India. BMC Public Health. 2022; 22 : 746. PubMed Abstract | Publisher Full Text | Free Full Text 10. Ghazali SS, Seman Z, Zainuddin NH, et al. : Prevalence and factors associated with multimorbidity among older adults in Malaysia: a population-based cross-sectional study. BMJ Open. 2021; 11 : e052126. PubMed Abstract | Publisher Full Text | Free Full Text 11. Masnoon N, Shakib S, Kalisch-Ellett L, et al. : What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017; 17 : 1. Publisher Full Text 12. Halli-Tierney AD, Scarbrough C, Carroll D: Polypharmacy: evaluating risks and deprescribing. Am Fam Physician. 2019; 100 : 32–38. PubMed Abstract 13. Toh JJ, Zhang H, Soh YY, et al. : Prevalence and health outcomes of polypharmacy and hyperpolypharmacy in older adults with frailty: A systematic review and meta-analysis. Ageing Res Rev. 2023; 83 : 101811. PubMed Abstract | Publisher Full Text 14. Nicholson K, Liu W, Fitzpatrick D, et al. : Prevalence of multimorbidity and polypharmacy among adults and older adults: a systematic review. Lancet Healthy Longev. 2024; 5 : E287–E296. Publisher Full Text 15. Cho HJ, Kim DS: Aging and the prevalence of polypharmacy and hyper-polypharmacy among older adults in South Korea: a national retrospective study during 2010–2019. Front Pharmacol. 2022; 13 : 866318. PubMed Abstract | Publisher Full Text | Free Full Text 16. Manirajan P, Sivanandy P: Drug utilisation review among geriatric patients with noncommunicable diseases in a primary care setting in Malaysia. Healthcare (Basel). 2023; 11 : 1665. PubMed Abstract | Publisher Full Text | Free Full Text 17. Aggarwal P, Woolford SJ, Patel HP: Multi-morbidity and polypharmacy in older people: challenges and opportunities for clinical practice. Geriatr. 2020; 5 : 85. PubMed Abstract | Publisher Full Text | Free Full Text 18. Pérez T, Moriarty F, Wallace E, et al. : Prevalence of potentially inappropriate prescribing in older people in primary care and its association with hospital admission: longitudinal study. BMJ. 2018; 363 : k4524. PubMed Abstract | Publisher Full Text | Free Full Text 19. Matthews S, Moriarty F, Ward M, et al. : Overprescribing among older people near end of life in Ireland: Evidence of prevalence and determinants from The Irish Longitudinal Study on Ageing (TILDA). PLos One. 2022; 17 : e0278127. PubMed Abstract | Publisher Full Text | Free Full Text 20. Safer DJ: Overprescribed medications for US adults: four major examples. J Clin Med Res. 2019; 11 : 617–622. PubMed Abstract | Publisher Full Text | Free Full Text 21. Hanna V, Chahine B, Al SF: Under-prescription of medications in older adults according to START criteria: A cross-sectional study in Lebanon. Health Sci Rep. 2022; 5 : e759. PubMed Abstract | Publisher Full Text | Free Full Text 22. Lombardi F, Paoletti L, Carrieri B, et al. : Underprescription of medications in older adults: causes, consequences and solutions—a narrative review. Eur Geriatr Med. 2021; 12 : 453–462. PubMed Abstract | Publisher Full Text 23. Lee GB, Etherton-Beer C, Hosking SM, et al. : The patterns and implications of potentially suboptimal medicine regimens among older adults: a narrative review. Ther Adv Drug Saf. 2022; 13 : 204209862211001. Publisher Full Text 24. Liew TM, Lee CS, Shawn KL, et al. : Potentially inappropriate prescribing among older persons: a meta-analysis of observational studies. Ann Fam Med. 2019; 17 : 257–266. PubMed Abstract | Publisher Full Text | Free Full Text 25. Salm C, Sauer J, Binder N, et al. : Over-and under-prescribing, and their association with functional disability in older patients at risk of further decline in Germany–a cross-sectional survey conducted as part of a randomised comparative effectiveness trial. BMC Geriatr. 2022; 22 : 564. PubMed Abstract | Publisher Full Text | Free Full Text 26. Kaminaga M, Komagamine J, Tatsumi S: The effects of in-hospital deprescribing on potential prescribing omission in hospitalized elderly patients with polypharmacy. Sci Rep. 2021; 11 : 8898. PubMed Abstract | Publisher Full Text | Free Full Text 27. Aremu TO, Oluwole OE, Adeyinka KO, et al. : Medication adherence and compliance: recipe for improving patient outcomes. Pharmacy (Basel). 2022; 10 : 106. PubMed Abstract | Publisher Full Text | Free Full Text 28. Smaje A, Weston-Clark M, Raj R, et al. : Factors associated with medication adherence in older patients: A systematic review. Aging Med (Milton). 2018; 1 : 254–266. PubMed Abstract | Publisher Full Text | Free Full Text 29. Mahmoodi H, Jalalizad Nahand F, Shaghaghi A, et al. : Gender based cognitive determinants of medication adherence in older adults with chronic conditions. Patient Prefer Adherence. 2019; 13 : 1733–1744. PubMed Abstract | Publisher Full Text | Free Full Text 30. Parker K, Bull-Engelstad I, Aasebø W, et al. : Medication regimen complexity and medication adherence in elderly patients with chronic kidney disease. Hemodial Int. 2019; 23 : 333–342. PubMed Abstract | Publisher Full Text 31. Wang X, Chen H, Essien E, et al. : Medication adherence to antihypertensive triple-combination therapy among patients enrolled in a medicare advantage plan. J Manag Care Spec Pharm. 2019; 25 : 678–686. PubMed Abstract | Publisher Full Text | Free Full Text 32. Lu J, Zhang N, Mao D, et al. : How social isolation and loneliness effect medication adherence among elderly with chronic diseases: An integrated theory and validated cross-sectional study. Arch Gerontol Geriatr. 2020; 90 : 104154. PubMed Abstract | Publisher Full Text 33. Saqlain M, Riaz A, Malik MN, et al. : Medication adherence and its association with health literacy and performance in activities of daily livings among elderly hypertensive patients in Islamabad, Pakistan. Medicina. 2019; 55 : 163. PubMed Abstract | Publisher Full Text | Free Full Text 34. Liu J, Yu Y, Yan S, et al. : Risk factors for self-reported medication adherence in community-dwelling older patients with multimorbidity and polypharmacy: a multicenter cross-sectional study. BMC Geriatr. 2023; 23 : 75. PubMed Abstract | Publisher Full Text | Free Full Text 35. Doherty AS, Boland F, Moriarty F, et al. : Adverse drug reactions and associated patient characteristics in older community-dwelling adults: a 6-year prospective cohort study. Br J Gen Pract. 2023; 73 : e211–e219. PubMed Abstract | Publisher Full Text | Free Full Text 36. Zazzara MB, Palmer K, Vetrano DL, et al. : Adverse drug reactions in older adults: a narrative review of the literature. Eur Geriatr Med. 2021; 12 : 463–473. PubMed Abstract | Publisher Full Text | Free Full Text 37. Osanlou R, Walker L, Hughes DA, et al. : Adverse drug reactions, multimorbidity and polypharmacy: a prospective analysis of 1 month of medical admissions. BMJ Open. 2022; 12 : e055551. PubMed Abstract | Publisher Full Text | Free Full Text 38. Woo SD, Yoon J, Doo GE, et al. : Common causes and characteristics of adverse drug reactions in older adults: a retrospective study. BMC Pharmacol. Toxicol. 2020; 21 : 1–9. 39. Dubrall D, Just KS, Schmid M, et al. : Adverse drug reactions in older adults: a retrospective comparative analysis of spontaneous reports to the German Federal Institute for Drugs and Medical Devices. BMC Pharmacol. Toxicol. 2020; 21 : 1–20. 40. Insani WN, Whittlesea C, Alwafi H, et al. : Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis. PLoS One. 2021; 16 : e0252161. PubMed Abstract | Publisher Full Text | Free Full Text 41. Jiang H, Lin Y, Ren W, et al. : Adverse drug reactions and correlations with drug–drug interactions: a retrospective study of reports from 2011 to 2020. Front Pharmacol. 2022; 13 : 923939. PubMed Abstract | Publisher Full Text | Free Full Text 42. Magro L, Arzenton E, Leone R, et al. : Identifying and characterizing serious adverse drug reactions associated with drug-drug interactions in a spontaneous reporting database. Front Pharmacol. 2021; 11 : 622862. PubMed Abstract | Publisher Full Text | Free Full Text 43. Rochon PA, Gurwitz JH: The prescribing cascade revisited. Lancet. 2017; 389 : 1778–1780. PubMed Abstract | Publisher Full Text 44. Maher D, Ailabouni N, Mangoni AA, et al. : Alterations in drug disposition in older adults: a focus on geriatric syndromes. Expert Opin Drug Metab Toxicol. 2021; 17 : 41–52. PubMed Abstract | Publisher Full Text 45. Davies A, Mundin G, Vriens J, et al. : The influence of low salivary flow rates on the absorption of a sublingual fentanyl citrate formulation for breakthrough cancer pain. J Pain Symptom Manag. 2016; 51 : 538–545. PubMed Abstract | Publisher Full Text 46. Dumic I, Nordin T, Jecmenica M, et al. : Gastrointestinal tract disorders in older age. Can J Gastroenterol Hepatol. 2019; 2019 : 6757524. 47. Azman M, Sabri AH, Anjani QK, et al. : Intestinal absorption study: Challenges and absorption enhancement strategies in improving oral drug delivery. Pharmaceuticals (Basel). 2022; 15 : 975. PubMed Abstract | Publisher Full Text | Free Full Text 48. Stillhart C, Vučićević K, Augustijns P, et al. : Impact of gastrointestinal physiology on drug absorption in special populations––An UNGAP review. Eur J Pharm Sci. 2020; 147 : 105280. PubMed Abstract | Publisher Full Text 49. Drenth-van Maanen AC, Wilting I, Jansen PA: Prescribing medicines to older people—How to consider the impact of ageing on human organ and body functions. Br J Clin Pharmacol. 2020; 86 : 1921–1930. PubMed Abstract | Publisher Full Text | Free Full Text 50. Soejima K, Sato H, Hisaka A: Age-related change in hepatic clearance inferred from multiple population pharmacokinetic studies: comparison with renal clearance and their associations with organ weight and blood flow. Clin Pharmacokinet. 2022; 61 : 295–305. PubMed Abstract | Publisher Full Text 51. Papacocea RI, Timofte D, Tanasescu MD, et al. : Kidney aging process and the management of the elderly patient with renal impairment (Review). Exp Ther Med. 2021; 21 : 266. PubMed Abstract | Publisher Full Text | Free Full Text 52. Fang Y, Gong AY, Haller ST, et al. : The ageing kidney: Molecular mechanisms and clinical implications. Ageing Res Rev. 2020; 63 : 101151. PubMed Abstract | Publisher Full Text | Free Full Text 53. Ma Y, Shen X, Yong Z, et al. : Comparison of glomerular filtration rate estimating equations in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr. 2023; 114 : 105107. PubMed Abstract | Publisher Full Text 54. Ghoneim AM, Mansour SM: The effect of liver and kidney disease on the pharmacokinetics of clozapine and sildenafil: a physiologically based pharmacokinetic modeling. Drug Des Devel Ther. 2020; 14 : 1469–1479. PubMed Abstract | Publisher Full Text | Free Full Text 55. Koren G, Nordon G, Radinsky K, et al. : Clinical pharmacology of old age. Expert Rev Clin Pharmacol. 2019; 12 : 749–755. Publisher Full Text 56. Peeters LE, Kester MP, Feyz L, et al. : Pharmacokinetic and pharmacodynamic considerations in the treatment of the elderly patient with hypertension. Expert Opin Drug Metab Toxicol. 2019; 15 : 287–297. PubMed Abstract | Publisher Full Text 57. Hilmer SN, Gnjidic D: The anticholinergic burden: from research to practice. Aust Prescr. 2022; 45 : 118–120. PubMed Abstract | Publisher Full Text | Free Full Text 58. Stewart C, Taylor-Rowan M, Soiza RL, et al. : Anticholinergic burden measures and older people’s falls risk: a systematic prognostic review. Ther Adv Drug Saf. 2021; 12 : 204209862110166. Publisher Full Text 59. Radcliffe E, Servin R, Cox N, et al. : What makes a multidisciplinary medication review and deprescribing intervention for older people work well in primary care? A realist review and synthesis. BMC Geriatr. 2023; 23 : 591. PubMed Abstract | Publisher Full Text | Free Full Text 60. Molist-Brunet N, Sevilla-Sánchez D, Puigoriol-Juvanteny E, et al. : Improving individualized prescription in patients with multimorbidity through medication review. BMC Geriatr. 2022; 22 : 417. PubMed Abstract | Publisher Full Text | Free Full Text 61. Madden M, Mills T, Atkin K, et al. : Early implementation of the structured medication review in England: a qualitative study. Br J Gen Pract. 2022; 72 : e641–e648. PubMed Abstract | Publisher Full Text | Free Full Text 62. Ming Y, Zecevic AA, Hunter SW, et al. : Medication review in preventing older adults’ fall-related injury: a systematic review & meta-analysis. Can Geriatr J. 2021; 24 : 237–250. PubMed Abstract | Publisher Full Text | Free Full Text 63. Wu H, Kouladjian O’Donnell L, Fujita K, et al. : Deprescribing in the older patient: a narrative review of challenges and solutions. Int J Gen Med. 2021; 14 : 3793–3807. PubMed Abstract | Publisher Full Text | Free Full Text 64. Woodford HJ, Fisher J: New horizons in deprescribing for older people. Age Ageing. 2019; 48 : 768–775. PubMed Abstract | Publisher Full Text 65. Ibrahim K, Cox NJ, Stevenson JM, et al. : A systematic review of the evidence for deprescribing interventions among older people living with frailty. BMC Geriatr. 2021; 21 : 1–6. Publisher Full Text 66. Anderson K, Freeman C, Foster M, et al. : GP-led deprescribing in community-living older Australians: an exploratory controlled trial. J Am Geriatr Soc. 2020; 68 : 403–410. PubMed Abstract | Publisher Full Text 67. Curtin D, Jennings E, Daunt R, et al. : Deprescribing in older people approaching end of life: a randomized controlled trial using STOPPFrail criteria. J Am Geriatr Soc. 2020; 68 : 762–769. PubMed Abstract | Publisher Full Text 68. Campbell NL, Pitts C, Corvari C, et al. : Deprescribing anticholinergics in primary care older adults: Experience from two models and impact on a continuous measure of exposure. J Am Coll Clin Pharm. 2022; 5 : 1039–1047. PubMed Abstract | Publisher Full Text | Free Full Text 69. Krishnaswami A, Steinman MA, Goyal P, et al. : Deprescribing in older adults with cardiovascular disease. J Am Coll Cardiol. 2019; 73 : 2584–2595. PubMed Abstract | Publisher Full Text | Free Full Text 70. Farrell B, Mangin D: Deprescribing is an essential part of good prescribing. Am Fam Physician. 2019; 99 : 7–9. PubMed Abstract 71. O’Mahony D, Cherubini A, Guiteras AR, et al. : STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023; 14 : 625–632. PubMed Abstract | Publisher Full Text | Free Full Text 72. Reeve E: Deprescribing tools: a review of the types of tools available to aid deprescribing in clinical practice. J Pharm Pract Res. 2020; 50 : 98–107. Publisher Full Text 73. McCarthy LM, Savage R, Dalton K, et al. : ThinkCascades: a tool for identifying clinically important prescribing cascades affecting older people. Drugs Aging. 2022; 39 : 829–840. PubMed Abstract | Publisher Full Text | Free Full Text 74. Nguyen QD, Moodie EM, Forget MF, et al. : Health heterogeneity in older adults: exploration in the Canadian longitudinal study on aging. J Am Geriatr Soc. 2021; 69 : 678–687. PubMed Abstract | Publisher Full Text 75. Jaul E, Barron J: Characterizing the heterogeneity of aging: a vision for a staging system for aging. Front Public Health. 2021; 9 : 513557. PubMed Abstract | Publisher Full Text | Free Full Text 76. Strain WD, Down S, Brown P, et al. : Diabetes and frailty: an expert consensus statement on the management of older adults with type 2 diabetes. Diabetes Ther. 2021; 12 : 1227–1247. PubMed Abstract | Publisher Full Text | Free Full Text 77. Rhalimi F, Rhalimi M, Rauss A: Pharmacist’s comprehensive geriatric assessment: introduction and evaluation at elderly patient admission. Drugs-Real World Outcomes. 2017; 4 : 43–51. PubMed Abstract | Publisher Full Text | Free Full Text 78. Manirajan P, Sivanandy P, Ingle PV: Enhancing knowledge, attitude, and perceptions towards fall prevention among older adults: a pharmacist-led intervention in a primary healthcare clinic, Gemas, Malaysia. BMC Geriatr. 2024; 24 : 309. PubMed Abstract | Publisher Full Text | Free Full Text 79. Yen PH, Leasure AR: Use and effectiveness of the teach-back method in patient education and health outcomes. Fed Pract. 2019; 36 : 284–289. PubMed Abstract 80. Bhattad PB, Pacifico L: Empowering patients: promoting patient education and health literacy. Cureus. 2022; 14 : e27336. Publisher Full Text 81. Ammerman CA, Simpkins BA, Warman N, et al. : Potentially inappropriate medications in older adults: deprescribing with a clinical pharmacist. J Am Geriatr Soc. 2019; 67 : 115–118. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 05 Jul 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Pharmacy Practice, School of Pharmacy, IMU University, Kuala Lumpur, 57000, Malaysia Priya Manirajan Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation Palanisamy Sivanandy Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Resources, Software, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 05 Jul 2024, 13:748 https://doi.org/10.12688/f1000research.152996.1 Copyright © 2024 Manirajan P and Sivanandy P. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Manirajan P and Sivanandy P. A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.12688/f1000research.152996.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 05 Jul 2024 Views 0 Cite How to cite this report: Albert S. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359204 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359204 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Feb 2025 Steven Albert , University of Pittsburgh, Pittsburgh, Pennsylvania, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.167828.r359204 This review is very helpful for summarizing the state of the art in prescribing for older adults. I appreciate the coverage of pharmacoepidemiology, the special challenges of aging physiology for assessing drug action, and clinical strategies for optimizing therapy. The ... Continue reading READ ALL This review is very helpful for summarizing the state of the art in prescribing for older adults. I appreciate the coverage of pharmacoepidemiology, the special challenges of aging physiology for assessing drug action, and clinical strategies for optimizing therapy. The discussion of medication review, patient education, and deprescribing is very topical. Perhaps one area to develop further, time permitting, is the role of pharmacists in optimizing therapy. Is medication review in the pharmacy feasible and effective?, Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Public health gerontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Albert S. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359204 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359204 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Antimisiaris D. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359202 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359202 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Jan 2025 Demetra Antimisiaris , University of Louisville, Louisville, Kentucky, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.167828.r359202 This review is important but it depends on the audience. The topic of optimization of pharmacotherapy is so vast that what this paper presents is a primer that is suitable for novice learners (like new pharmacy students or nursing students). ... Continue reading READ ALL This review is important but it depends on the audience. The topic of optimization of pharmacotherapy is so vast that what this paper presents is a primer that is suitable for novice learners (like new pharmacy students or nursing students). The algorithm is presented as if it is accepted science but in reality, the experts in the field do not reduce optimization of pharmacotherapy for older adults to this simplistic level. Also, the terminology in the algorithm requires a lot of explanation not present in the paper. Some of the early content is a nice review, but then later the citations do not support the statements adequately. And there are several statements that are not comprehensive nor explanatory as to why, but just a statement. Like "clear communication with both patient and family is essential to ensure everyone understands...." the reader might ask why is everyone understanding important? Aging population, PK sections are all conventional geriatric pharmacy review topics, and the authors wrote those sections well. PD section includes B receptors and anticholinergic, but there are so many other PD changes with age that at minimum that section should refer to those as examples of PD concerns. The authors could possibly list more PD examples and review some of the mechanisms of increased sensitivity to some or all of the drugs listed in the sentence “Increasing age can increase sensitivity to most drugs such as digoxin, warfarin, opioids, antipsychotics, and diuretics” In this section, optimizing pharmacotherapy in older adults: the following sentence is too definitive and simplistic and could mislead readers. “The following steps can be taken to overcome pharmacotherapy challenges in older adults:- unless the evidence explaining step by step (with cited research) is provided, that sentence sounds too definitive. Medication Review Section: the SMR presented is nothing more than what the paper’s title infers- “A Pharmacist Perspective”. The SMR is presented as if the algorithm presented is validated under validated clinical science and study yet is in reality a pharmacist’s perspective or rather the author's creation not through validated expert opinion methods nor through a study but just the author's perspective and the algorithm should probably be framed as such. That said, I agree with the components that should be considered in optimizing pharmacotherapy in older adults but there is so much more to it from a biomedical and clinical science perspective. When reviewing the steps in the presented algorithm, the reader asks in their mind about the exigence of each step (the details, how to, or what about). For example, I may have missed it earlier, but I think the first mention of the prescribing cascade is in this diagram. Some of the citations do not seem to match the statement. For example, citation #61 is in support of this section ending in sentence “The SMRs are intended for patients with hyperpolypharmacy, severe frailty, and potentially addictive pain management medications, which are commonly found in older adults.” …when the actual publication reports a focus group reporting gaps in stake holders training and perspectives in SMR implementation. Beyond this section there are a lot of similar issues with citations. Also there are statements not supported by robust explanations nor citations to support. For example: “A multidisciplinary approach is beneficial for optimizing pharmacotherapy. The team can include geriatricians, physicians, pharmacists, nurses, dieticians, physiotherapists, and other specialists. By combining expertise from various disciplines, the team can gain a holistic understanding of the patient’s health, including medical conditions, cognitive function, and social circumstances. This allows for a more individualized medication plan.” Where is the explanation of how and why a multidisciplinary approach is beneficial and what citations support this idea? SUGGESTION: This paper could be more viable as an opinion article or brief report (but as brief report it would even need more fine tuning). I truly appreciate the topic, and that people care to write about it. So, I don't mean to be discouraging to the authors and hope to offer this feedback in the spirit of encouraging robustness or framing in alignment with the existing content. I commend the authors for doing this work- and especially as polypharmacy grows globally and with an aging population, we need more of this type of content! Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Polypharmacy, geriatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Antimisiaris D. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359202 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359202 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Matsumoto A. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r319107 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-319107 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 25 Sep 2024 Ayaka Matsumoto , Kumamoto Rehabilitation Hospital, Kumamoto, Japan Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.167828.r319107 I believe this paper is important as it reviews the key considerations for optimizing drug therapy in the older adults. However, I have several concerns and would like to propose the following revisions: Novelty ... Continue reading READ ALL I believe this paper is important as it reviews the key considerations for optimizing drug therapy in the older adults. However, I have several concerns and would like to propose the following revisions: Novelty and Differentiation: While the paper provides a comprehensive review, it would benefit from a clearer emphasis on what makes it unique compared to other similar reviews. Highlight specific angles or methods that distinguish this paper from the existing literature. Focus on True Health Outcomes: While the paper acknowledges the benefits of medication optimization in reducing the number of drugs, PIMs, and anticholinergic load, it should go further by discussing outcomes directly affecting the elderly's quality of life. It would be useful to include data on physical function, ADL (activities of daily living), quality of life, and mortality in elderly populations. Studies like the one in reference(PMID: 35633757) that show the impact of medication reviews on optimizing therapy and health outcomes could be cited. Insufficient Citations: The paper lacks references in critical sections, such as the one on "Promote patient autonomy & shared decision-making." Adding recent systematic reviews and relevant research will strengthen the paper's academic depth. Consider citing the latest studies that discuss optimizing drug therapy outcomes in the elderly, particularly those focused on shared decision-making models. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Polypharmacy in Rehabilitation Medicine, Clinical Nutrition I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Matsumoto A. Reviewer Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r319107 ) The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-319107 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 05 Jul 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 1 05 Jul 24 read read read Ayaka Matsumoto , Kumamoto Rehabilitation Hospital, Kumamoto, Japan Demetra Antimisiaris , University of Louisville, Louisville, USA Steven Albert , University of Pittsburgh, Pittsburgh, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Albert S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 18 Feb 2025 | for Version 1 Steven Albert , University of Pittsburgh, Pittsburgh, Pennsylvania, USA 0 Views copyright © 2025 Albert S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This review is very helpful for summarizing the state of the art in prescribing for older adults. I appreciate the coverage of pharmacoepidemiology, the special challenges of aging physiology for assessing drug action, and clinical strategies for optimizing therapy. The discussion of medication review, patient education, and deprescribing is very topical. Perhaps one area to develop further, time permitting, is the role of pharmacists in optimizing therapy. Is medication review in the pharmacy feasible and effective?, Is the topic of the review discussed comprehensively in the context of the current literature? Yes Are all factual statements correct and adequately supported by citations? Yes Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Public health gerontology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Albert S. Peer Review Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359204) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359204 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Antimisiaris D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Jan 2025 | for Version 1 Demetra Antimisiaris , University of Louisville, Louisville, Kentucky, USA 0 Views copyright © 2025 Antimisiaris D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This review is important but it depends on the audience. The topic of optimization of pharmacotherapy is so vast that what this paper presents is a primer that is suitable for novice learners (like new pharmacy students or nursing students). The algorithm is presented as if it is accepted science but in reality, the experts in the field do not reduce optimization of pharmacotherapy for older adults to this simplistic level. Also, the terminology in the algorithm requires a lot of explanation not present in the paper. Some of the early content is a nice review, but then later the citations do not support the statements adequately. And there are several statements that are not comprehensive nor explanatory as to why, but just a statement. Like "clear communication with both patient and family is essential to ensure everyone understands...." the reader might ask why is everyone understanding important? Aging population, PK sections are all conventional geriatric pharmacy review topics, and the authors wrote those sections well. PD section includes B receptors and anticholinergic, but there are so many other PD changes with age that at minimum that section should refer to those as examples of PD concerns. The authors could possibly list more PD examples and review some of the mechanisms of increased sensitivity to some or all of the drugs listed in the sentence “Increasing age can increase sensitivity to most drugs such as digoxin, warfarin, opioids, antipsychotics, and diuretics” In this section, optimizing pharmacotherapy in older adults: the following sentence is too definitive and simplistic and could mislead readers. “The following steps can be taken to overcome pharmacotherapy challenges in older adults:- unless the evidence explaining step by step (with cited research) is provided, that sentence sounds too definitive. Medication Review Section: the SMR presented is nothing more than what the paper’s title infers- “A Pharmacist Perspective”. The SMR is presented as if the algorithm presented is validated under validated clinical science and study yet is in reality a pharmacist’s perspective or rather the author's creation not through validated expert opinion methods nor through a study but just the author's perspective and the algorithm should probably be framed as such. That said, I agree with the components that should be considered in optimizing pharmacotherapy in older adults but there is so much more to it from a biomedical and clinical science perspective. When reviewing the steps in the presented algorithm, the reader asks in their mind about the exigence of each step (the details, how to, or what about). For example, I may have missed it earlier, but I think the first mention of the prescribing cascade is in this diagram. Some of the citations do not seem to match the statement. For example, citation #61 is in support of this section ending in sentence “The SMRs are intended for patients with hyperpolypharmacy, severe frailty, and potentially addictive pain management medications, which are commonly found in older adults.” …when the actual publication reports a focus group reporting gaps in stake holders training and perspectives in SMR implementation. Beyond this section there are a lot of similar issues with citations. Also there are statements not supported by robust explanations nor citations to support. For example: “A multidisciplinary approach is beneficial for optimizing pharmacotherapy. The team can include geriatricians, physicians, pharmacists, nurses, dieticians, physiotherapists, and other specialists. By combining expertise from various disciplines, the team can gain a holistic understanding of the patient’s health, including medical conditions, cognitive function, and social circumstances. This allows for a more individualized medication plan.” Where is the explanation of how and why a multidisciplinary approach is beneficial and what citations support this idea? SUGGESTION: This paper could be more viable as an opinion article or brief report (but as brief report it would even need more fine tuning). I truly appreciate the topic, and that people care to write about it. So, I don't mean to be discouraging to the authors and hope to offer this feedback in the spirit of encouraging robustness or framing in alignment with the existing content. I commend the authors for doing this work- and especially as polypharmacy grows globally and with an aging population, we need more of this type of content! Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Polypharmacy, geriatrics I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Antimisiaris D. Peer Review Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r359202) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-359202 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Matsumoto A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 Sep 2024 | for Version 1 Ayaka Matsumoto , Kumamoto Rehabilitation Hospital, Kumamoto, Japan 0 Views copyright © 2024 Matsumoto A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I believe this paper is important as it reviews the key considerations for optimizing drug therapy in the older adults. However, I have several concerns and would like to propose the following revisions: Novelty and Differentiation: While the paper provides a comprehensive review, it would benefit from a clearer emphasis on what makes it unique compared to other similar reviews. Highlight specific angles or methods that distinguish this paper from the existing literature. Focus on True Health Outcomes: While the paper acknowledges the benefits of medication optimization in reducing the number of drugs, PIMs, and anticholinergic load, it should go further by discussing outcomes directly affecting the elderly's quality of life. It would be useful to include data on physical function, ADL (activities of daily living), quality of life, and mortality in elderly populations. Studies like the one in reference(PMID: 35633757) that show the impact of medication reviews on optimizing therapy and health outcomes could be cited. Insufficient Citations: The paper lacks references in critical sections, such as the one on "Promote patient autonomy & shared decision-making." Adding recent systematic reviews and relevant research will strengthen the paper's academic depth. Consider citing the latest studies that discuss optimizing drug therapy outcomes in the elderly, particularly those focused on shared decision-making models. Is the topic of the review discussed comprehensively in the context of the current literature? Partly Are all factual statements correct and adequately supported by citations? No Is the review written in accessible language? Yes Are the conclusions drawn appropriate in the context of the current research literature? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Polypharmacy in Rehabilitation Medicine, Clinical Nutrition I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Matsumoto A. Peer Review Report For: A Pharmacist Perspective on Optimizing Pharmacotherapy among Older Adults – A Review [version 1; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 13 :748 ( https://doi.org/10.5256/f1000research.167828.r319107) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-748/v1#referee-response-319107 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "A Pharmacist Perspective on Optimizing Pharmacotherapy...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/13-748/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/13-748/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/13-748/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Manirajan P and Sivanandy P'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/13-748/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/13-748", templates : { twitter : "A Pharmacist Perspective on Optimizing Pharmacotherapy among.... Manirajan P and Sivanandy P, published by " + "@F1000Research" + ", https://f1000research.com/articles/13-748/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/152996/167828") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "167828"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "319106": 0, "319107": 4, "326556": 0, "326558": 0, "359205": 0, "359204": 1, "327078": 0, "359207": 0, "327079": 0, "359206": 0, "359203": 0, "359202": 3, "359209": 0, "359208": 0, "359211": 0, "359210": 0, "315060": 0, "315061": 0, "315062": 0, "315063": 0, "315059": 0, "315068": 0, "308029": 0, "308030": 0, "308031": 0, "315064": 0, "315065": 0, "315066": 0, "315067": 0, "308036": 0, "308037": 0, "308038": 0, "308032": 0, "308033": 0, "308034": 0, "308035": 0, "302924": 0, "302925": 0, "302926": 0, "302927": 0, "302932": 0, "302933": 0, "302928": 0, "302929": 0, "302930": 0, "302931": 0, "312284": 0, "312285": 0, "312286": 0, "312287": 0, "312283": 0, "312292": 0, "312288": 0, "312289": 0, "312290": 0, "312291": 0, "322548": 0, "322549": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "79be95f8-2396-47be-89f6-a76ddaa9a85b"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });