+
${missingFields[0]} field.`,
+ message: `The items being returned for this search do not include all the required fields. Please ensure that your index items include the ${missingFields[0]} field or use index-fields in your _quarto.yml file to specify the field names.`,
+ };
+ } else if (missingFields.length > 1) {
+ const missingFieldList = missingFields
+ .map((field) => {
+ return `${field}`;
+ })
+ .join(", ");
+
+ throw {
+ name: `Error: Search index is missing the following fields: ${missingFieldList}.`,
+ message: `The items being returned for this search do not include all the required fields. Please ensure that your index items includes the following fields: ${missingFieldList}, or use index-fields in your _quarto.yml file to specify the field names.`,
+ };
+ }
+ }
+}
+
+let lastQuery = null;
+function showCopyLink(query, options) {
+ const language = options.language;
+ lastQuery = query;
+ // Insert share icon
+ const inputSuffixEl = window.document.body.querySelector(
+ ".aa-Form .aa-InputWrapperSuffix"
+ );
+
+ if (inputSuffixEl) {
+ let copyButtonEl = window.document.body.querySelector(
+ ".aa-Form .aa-InputWrapperSuffix .aa-CopyButton"
+ );
+
+ if (copyButtonEl === null) {
+ copyButtonEl = window.document.createElement("button");
+ copyButtonEl.setAttribute("class", "aa-CopyButton");
+ copyButtonEl.setAttribute("type", "button");
+ copyButtonEl.setAttribute("title", language["search-copy-link-title"]);
+ copyButtonEl.onmousedown = (e) => {
+ e.preventDefault();
+ e.stopPropagation();
+ };
+
+ const linkIcon = "bi-clipboard";
+ const checkIcon = "bi-check2";
+
+ const shareIconEl = window.document.createElement("i");
+ shareIconEl.setAttribute("class", `bi ${linkIcon}`);
+ copyButtonEl.appendChild(shareIconEl);
+ inputSuffixEl.prepend(copyButtonEl);
+
+ const clipboard = new window.ClipboardJS(".aa-CopyButton", {
+ text: function (_trigger) {
+ const copyUrl = new URL(window.location);
+ copyUrl.searchParams.set(kQueryArg, lastQuery);
+ copyUrl.searchParams.set(kResultsArg, "1");
+ return copyUrl.toString();
+ },
+ });
+ clipboard.on("success", function (e) {
+ // Focus the input
+
+ // button target
+ const button = e.trigger;
+ const icon = button.querySelector("i.bi");
+
+ // flash "checked"
+ icon.classList.add(checkIcon);
+ icon.classList.remove(linkIcon);
+ setTimeout(function () {
+ icon.classList.remove(checkIcon);
+ icon.classList.add(linkIcon);
+ }, 1000);
+ });
+ }
+
+ // If there is a query, show the link icon
+ if (copyButtonEl) {
+ if (lastQuery && options["copy-button"]) {
+ copyButtonEl.style.display = "flex";
+ } else {
+ copyButtonEl.style.display = "none";
+ }
+ }
+ }
+}
+
+/* Search Index Handling */
+// create the index
+var fuseIndex = undefined;
+async function readSearchData() {
+ // Initialize the search index on demand
+ if (fuseIndex === undefined) {
+ // create fuse index
+ const options = {
+ keys: [
+ { name: "title", weight: 20 },
+ { name: "section", weight: 20 },
+ { name: "text", weight: 10 },
+ ],
+ ignoreLocation: true,
+ threshold: 0.1,
+ };
+ const fuse = new window.Fuse([], options);
+
+ // fetch the main search.json
+ const response = await fetch(offsetURL("search.json"));
+ if (response.status == 200) {
+ return response.json().then(function (searchDocs) {
+ searchDocs.forEach(function (searchDoc) {
+ fuse.add(searchDoc);
+ });
+ fuseIndex = fuse;
+ return fuseIndex;
+ });
+ } else {
+ return Promise.reject(
+ new Error(
+ "Unexpected status from search index request: " + response.status
+ )
+ );
+ }
+ }
+ return fuseIndex;
+}
+
+function inputElement() {
+ return window.document.body.querySelector(".aa-Form .aa-Input");
+}
+
+function focusSearchInput() {
+ setTimeout(() => {
+ const inputEl = inputElement();
+ if (inputEl) {
+ inputEl.focus();
+ }
+ }, 50);
+}
+
+/* Panels */
+const kItemTypeDoc = "document";
+const kItemTypeMore = "document-more";
+const kItemTypeItem = "document-item";
+const kItemTypeError = "error";
+
+function renderItem(
+ item,
+ createElement,
+ state,
+ setActiveItemId,
+ setContext,
+ refresh
+) {
+ switch (item.type) {
+ case kItemTypeDoc:
+ return createDocumentCard(
+ createElement,
+ "file-richtext",
+ item.title,
+ item.section,
+ item.text,
+ item.href
+ );
+ case kItemTypeMore:
+ return createMoreCard(
+ createElement,
+ item,
+ state,
+ setActiveItemId,
+ setContext,
+ refresh
+ );
+ case kItemTypeItem:
+ return createSectionCard(
+ createElement,
+ item.section,
+ item.text,
+ item.href
+ );
+ case kItemTypeError:
+ return createErrorCard(createElement, item.title, item.text);
+ default:
+ return undefined;
+ }
+}
+
+function createDocumentCard(createElement, icon, title, section, text, href) {
+ const iconEl = createElement("i", {
+ class: `bi bi-${icon} search-result-icon`,
+ });
+ const titleEl = createElement("p", { class: "search-result-title" }, title);
+ const titleContainerEl = createElement(
+ "div",
+ { class: "search-result-title-container" },
+ [iconEl, titleEl]
+ );
+
+ const textEls = [];
+ if (section) {
+ const sectionEl = createElement(
+ "p",
+ { class: "search-result-section" },
+ section
+ );
+ textEls.push(sectionEl);
+ }
+ const descEl = createElement("p", {
+ class: "search-result-text",
+ dangerouslySetInnerHTML: {
+ __html: text,
+ },
+ });
+ textEls.push(descEl);
+
+ const textContainerEl = createElement(
+ "div",
+ { class: "search-result-text-container" },
+ textEls
+ );
+
+ const containerEl = createElement(
+ "div",
+ {
+ class: "search-result-container",
+ },
+ [titleContainerEl, textContainerEl]
+ );
+
+ const linkEl = createElement(
+ "a",
+ {
+ href: offsetURL(href),
+ class: "search-result-link",
+ },
+ containerEl
+ );
+
+ const classes = ["search-result-doc", "search-item"];
+ if (!section) {
+ classes.push("document-selectable");
+ }
+
+ return createElement(
+ "div",
+ {
+ class: classes.join(" "),
+ },
+ linkEl
+ );
+}
+
+function createMoreCard(
+ createElement,
+ item,
+ state,
+ setActiveItemId,
+ setContext,
+ refresh
+) {
+ const moreCardEl = createElement(
+ "div",
+ {
+ class: "search-result-more search-item",
+ onClick: (e) => {
+ // Handle expanding the sections by adding the expanded
+ // section to the list of expanded sections
+ toggleExpanded(item, state, setContext, setActiveItemId, refresh);
+ e.stopPropagation();
+ },
+ },
+ item.title
+ );
+
+ return moreCardEl;
+}
+
+function toggleExpanded(item, state, setContext, setActiveItemId, refresh) {
+ const expanded = state.context.expanded || [];
+ if (expanded.includes(item.target)) {
+ setContext({
+ expanded: expanded.filter((target) => target !== item.target),
+ });
+ } else {
+ setContext({ expanded: [...expanded, item.target] });
+ }
+
+ refresh();
+ setActiveItemId(item.__autocomplete_id);
+}
+
+function createSectionCard(createElement, section, text, href) {
+ const sectionEl = createSection(createElement, section, text, href);
+ return createElement(
+ "div",
+ {
+ class: "search-result-doc-section search-item",
+ },
+ sectionEl
+ );
+}
+
+function createSection(createElement, title, text, href) {
+ const descEl = createElement("p", {
+ class: "search-result-text",
+ dangerouslySetInnerHTML: {
+ __html: text,
+ },
+ });
+
+ const titleEl = createElement("p", { class: "search-result-section" }, title);
+ const linkEl = createElement(
+ "a",
+ {
+ href: offsetURL(href),
+ class: "search-result-link",
+ },
+ [titleEl, descEl]
+ );
+ return linkEl;
+}
+
+function createErrorCard(createElement, title, text) {
+ const descEl = createElement("p", {
+ class: "search-error-text",
+ dangerouslySetInnerHTML: {
+ __html: text,
+ },
+ });
+
+ const titleEl = createElement("p", {
+ class: "search-error-title",
+ dangerouslySetInnerHTML: {
+ __html: ` ${title}`,
+ },
+ });
+ const errorEl = createElement("div", { class: "search-error" }, [
+ titleEl,
+ descEl,
+ ]);
+ return errorEl;
+}
+
+function positionPanel(pos) {
+ const panelEl = window.document.querySelector(
+ "#quarto-search-results .aa-Panel"
+ );
+ const inputEl = window.document.querySelector(
+ "#quarto-search .aa-Autocomplete"
+ );
+
+ if (panelEl && inputEl) {
+ panelEl.style.top = `${Math.round(panelEl.offsetTop)}px`;
+ if (pos === "start") {
+ panelEl.style.left = `${Math.round(inputEl.left)}px`;
+ } else {
+ panelEl.style.right = `${Math.round(inputEl.offsetRight)}px`;
+ }
+ }
+}
+
+/* Highlighting */
+// highlighting functions
+function highlightMatch(query, text) {
+ if (text) {
+ const start = text.toLowerCase().indexOf(query.toLowerCase());
+ if (start !== -1) {
+ const startMark = "";
+ const endMark = "";
+
+ const end = start + query.length;
+ text =
+ text.slice(0, start) +
+ startMark +
+ text.slice(start, end) +
+ endMark +
+ text.slice(end);
+ const startInfo = clipStart(text, start);
+ const endInfo = clipEnd(
+ text,
+ startInfo.position + startMark.length + endMark.length
+ );
+ text =
+ startInfo.prefix +
+ text.slice(startInfo.position, endInfo.position) +
+ endInfo.suffix;
+
+ return text;
+ } else {
+ return text;
+ }
+ } else {
+ return text;
+ }
+}
+
+function clipStart(text, pos) {
+ const clipStart = pos - 50;
+ if (clipStart < 0) {
+ // This will just return the start of the string
+ return {
+ position: 0,
+ prefix: "",
+ };
+ } else {
+ // We're clipping before the start of the string, walk backwards to the first space.
+ const spacePos = findSpace(text, pos, -1);
+ return {
+ position: spacePos.position,
+ prefix: "",
+ };
+ }
+}
+
+function clipEnd(text, pos) {
+ const clipEnd = pos + 200;
+ if (clipEnd > text.length) {
+ return {
+ position: text.length,
+ suffix: "",
+ };
+ } else {
+ const spacePos = findSpace(text, clipEnd, 1);
+ return {
+ position: spacePos.position,
+ suffix: spacePos.clipped ? "…" : "",
+ };
+ }
+}
+
+function findSpace(text, start, step) {
+ let stepPos = start;
+ while (stepPos > -1 && stepPos < text.length) {
+ const char = text[stepPos];
+ if (char === " " || char === "," || char === ":") {
+ return {
+ position: step === 1 ? stepPos : stepPos - step,
+ clipped: stepPos > 1 && stepPos < text.length,
+ };
+ }
+ stepPos = stepPos + step;
+ }
+
+ return {
+ position: stepPos - step,
+ clipped: false,
+ };
+}
+
+// removes highlighting as implemented by the mark tag
+function clearHighlight(searchterm, el) {
+ const childNodes = el.childNodes;
+ for (let i = childNodes.length - 1; i >= 0; i--) {
+ const node = childNodes[i];
+ if (node.nodeType === Node.ELEMENT_NODE) {
+ if (
+ node.tagName === "MARK" &&
+ node.innerText.toLowerCase() === searchterm.toLowerCase()
+ ) {
+ el.replaceChild(document.createTextNode(node.innerText), node);
+ } else {
+ clearHighlight(searchterm, node);
+ }
+ }
+ }
+}
+
+function escapeRegExp(string) {
+ return string.replace(/[.*+?^${}()|[\]\\]/g, "\\$&"); // $& means the whole matched string
+}
+
+// highlight matches
+function highlight(term, el) {
+ const termRegex = new RegExp(term, "ig");
+ const childNodes = el.childNodes;
+
+ // walk back to front avoid mutating elements in front of us
+ for (let i = childNodes.length - 1; i >= 0; i--) {
+ const node = childNodes[i];
+
+ if (node.nodeType === Node.TEXT_NODE) {
+ // Search text nodes for text to highlight
+ const text = node.nodeValue;
+
+ let startIndex = 0;
+ let matchIndex = text.search(termRegex);
+ if (matchIndex > -1) {
+ const markFragment = document.createDocumentFragment();
+ while (matchIndex > -1) {
+ const prefix = text.slice(startIndex, matchIndex);
+ markFragment.appendChild(document.createTextNode(prefix));
+
+ const mark = document.createElement("mark");
+ mark.appendChild(
+ document.createTextNode(
+ text.slice(matchIndex, matchIndex + term.length)
+ )
+ );
+ markFragment.appendChild(mark);
+
+ startIndex = matchIndex + term.length;
+ matchIndex = text.slice(startIndex).search(new RegExp(term, "ig"));
+ if (matchIndex > -1) {
+ matchIndex = startIndex + matchIndex;
+ }
+ }
+ if (startIndex < text.length) {
+ markFragment.appendChild(
+ document.createTextNode(text.slice(startIndex, text.length))
+ );
+ }
+
+ el.replaceChild(markFragment, node);
+ }
+ } else if (node.nodeType === Node.ELEMENT_NODE) {
+ // recurse through elements
+ highlight(term, node);
+ }
+ }
+}
+
+/* Link Handling */
+// get the offset from this page for a given site root relative url
+function offsetURL(url) {
+ var offset = getMeta("quarto:offset");
+ return offset ? offset + url : url;
+}
+
+// read a meta tag value
+function getMeta(metaName) {
+ var metas = window.document.getElementsByTagName("meta");
+ for (let i = 0; i < metas.length; i++) {
+ if (metas[i].getAttribute("name") === metaName) {
+ return metas[i].getAttribute("content");
+ }
+ }
+ return "";
+}
+
+function algoliaSearch(query, limit, algoliaOptions) {
+ const { getAlgoliaResults } = window["@algolia/autocomplete-preset-algolia"];
+
+ const applicationId = algoliaOptions["application-id"];
+ const searchOnlyApiKey = algoliaOptions["search-only-api-key"];
+ const indexName = algoliaOptions["index-name"];
+ const indexFields = algoliaOptions["index-fields"];
+ const searchClient = window.algoliasearch(applicationId, searchOnlyApiKey);
+ const searchParams = algoliaOptions["params"];
+ const searchAnalytics = !!algoliaOptions["analytics-events"];
+
+ return getAlgoliaResults({
+ searchClient,
+ queries: [
+ {
+ indexName: indexName,
+ query,
+ params: {
+ hitsPerPage: limit,
+ clickAnalytics: searchAnalytics,
+ ...searchParams,
+ },
+ },
+ ],
+ transformResponse: (response) => {
+ if (!indexFields) {
+ return response.hits.map((hit) => {
+ return hit.map((item) => {
+ return {
+ ...item,
+ text: highlightMatch(query, item.text),
+ };
+ });
+ });
+ } else {
+ const remappedHits = response.hits.map((hit) => {
+ return hit.map((item) => {
+ const newItem = { ...item };
+ ["href", "section", "title", "text"].forEach((keyName) => {
+ const mappedName = indexFields[keyName];
+ if (
+ mappedName &&
+ item[mappedName] !== undefined &&
+ mappedName !== keyName
+ ) {
+ newItem[keyName] = item[mappedName];
+ delete newItem[mappedName];
+ }
+ });
+ newItem.text = highlightMatch(query, newItem.text);
+ return newItem;
+ });
+ });
+ return remappedHits;
+ }
+ },
+ });
+}
+
+function fuseSearch(query, fuse, fuseOptions) {
+ return fuse.search(query, fuseOptions).map((result) => {
+ const addParam = (url, name, value) => {
+ const anchorParts = url.split("#");
+ const baseUrl = anchorParts[0];
+ const sep = baseUrl.search("\\?") > 0 ? "&" : "?";
+ anchorParts[0] = baseUrl + sep + name + "=" + value;
+ return anchorParts.join("#");
+ };
+
+ return {
+ title: result.item.title,
+ section: result.item.section,
+ href: addParam(result.item.href, kQueryArg, query),
+ text: highlightMatch(query, result.item.text),
+ };
+ });
+}
diff --git a/_site/styles.css b/_site/styles.css
new file mode 100644
index 0000000..2ddf50c
--- /dev/null
+++ b/_site/styles.css
@@ -0,0 +1 @@
+/* css styles */
diff --git a/index.qmd b/index.qmd
new file mode 100644
index 0000000..ef49d41
--- /dev/null
+++ b/index.qmd
@@ -0,0 +1,11 @@
+---
+title: "personal-website"
+---
+
+This is a Quarto website.
+
+To learn more about Quarto websites visit There has been rising interest in using model‐informed precision dosing to provide personalized medicine to patients at the bedside. This methodology utilizes population pharmacokinetic models, measured drug concentrations from individual patients, pharmacodynamic biomarkers, and Bayesian estimation to estimate pharmacokinetic parameters and predict concentration‐time profiles in individual patients. Using these individualized parameter estimates and simulated drug exposure, dosing recommendations can be generated to maximize target attainment to improve beneficial effect and minimize toxicity. However, the accuracy of the output from this evaluation is highly dependent on the population pharmacokinetic model selected. This tutorial provides a comprehensive approach to evaluating, selecting, and validating a model for input and implementation into a model‐informed precision dosing program. A step‐by‐step outline to validate successful implementation into a precision dosing tool is described using the clinical software platforms Edsim++ and MwPharm++ as examples.
}, + author = {Zachary L. Taylor and Ethan A. Poweleit and Kelli Paice and Katherine M. Somers and Kathryn Pavia and Alexander A. Vinks and Nieko Punt and Tomoyuki Mizuno and Sonya Tang Girdwood}, + doi = {10.1002/psp4.13056}, + issn = {2163-8306}, + issue = {12}, + journal = {CPT: Pharmacometrics & Systems Pharmacology}, + month = {12}, + pages = {1827-1845}, + title = {Tutorial on model selection and validation of model input into precision dosing software for model‐informed precision dosing}, + volume = {12}, + year = {2023}, +} +@article{sandborn2002, + author = {William J. Sandborn and Stephen B. Hanauer}, + doi = {10.1111/j.1572-0241.2002.07093.x}, + issn = {0002-9270}, + issue = {12}, + journal = {American Journal of Gastroenterology}, + month = {12}, + pages = {2962-2972}, + title = {Infliximab in the Treatment of Crohn's Disease: A User's Guide for Clinicians}, + volume = {97}, + year = {2002}, +} +@article{Hooijmaijers2023, + abstract = {Establishing a dosing regimen that maximizes clinical benefit and minimizes adverse effects for novel therapeutics is a key objective for drug developers. Finding an optimal dose and schedule can be particularly challenging for compounds with a narrow therapeutic window such as in oncology. Modeling and simulation tools can be valuable to conduct in silico evaluations of various dosing scenarios with the goal to identify those that could minimize toxicities, avoid unscheduled dose interruptions, or minimize premature discontinuations, which all could limit the potential for therapeutic benefit. In this tutorial, we present a stepwise development of an adaptive dose simulation framework that can be used for dose optimization simulations. The tutorial first describes the general workflow, followed by a technical description with basic to advanced practical examples of its implementation in mrgsolve and is concluded with examples on how to use this in decision‐making around dose and schedule optimization. The adaptive simulation framework is built with pharmacokinetic, pharmacodynamic (i.e., biomarkers, activity markers, target engagement markers, efficacy markers), and safety models that include evaluations of unexplained interindividual and intraindividual variability and covariate impact, which can be replaced and expanded (e.g., combination setting, comparator setting) with user‐defined models. Subsequent adaptive simulations allow investigation of the impact of starting dose, dosing intervals, and event‐driven (exposure or effect) dose modifications on any end point. The resulting simulation‐derived insights can be used in quantitatively proposing dose and regimens that better balance benefit and adverse effects for further evaluation, aiding dose selection discussions, and designing dose modification recommendations, among others.
}, + author = {Richard Hooijmaijers and Ridhi Parasrampuria and Eleonora Marostica and Geraldine Ferron‐Brady and Teun M. Post and Sandra A. G. Visser}, + doi = {10.1002/psp4.13027}, + issn = {2163-8306}, + journal = {CPT: Pharmacometrics & Systems Pharmacology}, + month = {9}, + title = {Building an adaptive dose simulation framework to aid dose and schedule selection}, + year = {2023}, +} +@article{syversen2021, + author = {Silje Watterdal Syversen and Kristin Kaasen Jørgensen and Guro Løvik Goll and Marthe Kirkesæther Brun and Øystein Sandanger and Kristin Hammersbøen Bjørlykke and Joseph Sexton and Inge Christoffer Olsen and Johanna Elin Gehin and David John Warren and Rolf Anton Klaasen and Geir Noraberg and Trude Jannecke Bruun and Christian Kvikne Dotterud and Maud Kristine Aga Ljoså and Anne Julsrud Haugen and Rune Johan Njålla and Camilla Zettel and Carl Magnus Ystrøm and Yngvill Hovde Bragnes and Svanaug Skorpe and Turid Thune and Kathrine Aglen Seeberg and Brigitte Michelsen and Ingrid Marianne Blomgren and Eldri Kveine Strand and Pawel Mielnik and Roald Torp and Cato Mørk and Tore K. Kvien and Jørgen Jahnsen and Nils Bolstad and Espen A. Haavardsholm}, + doi = {10.1001/jama.2021.21316}, + issn = {0098-7484}, + issue = {23}, + journal = {JAMA}, + month = {12}, + pages = {2375}, + title = {Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases}, + volume = {326}, + year = {2021}, +} diff --git a/styles.css b/styles.css new file mode 100644 index 0000000..2ddf50c --- /dev/null +++ b/styles.css @@ -0,0 +1 @@ +/* css styles */