The calcitonin gene-related peptide monoclonal antibodies (CGRP MABs) erenumab, fremanezumab, and galcanezumab are reimbursed in Ireland under the High Tech Arrangement, subject to a managed access protocol (MAP), for the prophylaxis of chronic migraine in adults in whom three or more prophylactic treatments have failed. This study provides an overview of submitted reimbursement applications and the utilization of CGRP MABs.

The MAP for CGRP MABs was introduced on 1 September 2021 and is operated by the Health Service Executive (HSE) Medicines Management Programme. Individual patient reimbursement applications for CGRP MABs submitted through an online reimbursement application system between 1 September 2021 and 30 April 2023 were reviewed. Utilization data from 1 September 2021 to 30 April 2023 were extracted from the HSE Primary Care Reimbursement Service national pharmacy reimbursement claims database for the High Tech Arrangement. Analysis was performed using SAS® 9.4 software.

A total of 1,517 reimbursement applications were submitted in the study period. Reimbursement was approved for 96.1 percent (n=1,458) of the applications. A total of 1,399 individual patients (mean age 45 years) were dispensed a CGRP MAB under the High Tech Arrangement between September 2021 and April 2023, the majority of whom were women (n=1,141). Almost 90 percent of patients were considered treatment adherent. In April 2023, the market share of the individual CGRP MABs on the High Tech Arrangement was 56 percent (n=599) for fremanezumab, 38.3 percent (n=409) for erenumab, and 5.7 percent (n=61) for galcanezumab.

MAPs are part of the health technology management approach to drug reimbursement in the Irish healthcare setting, ensuring that reimbursement is in line with approved subgroups of the licensed indication. Used in conjunction with health technology assessment, MAPs enable access to high-cost drug treatments for patients with the greatest unmet need, while providing budgetary oversight and certainty for the payer.

Increasingly in Ireland, there are specific criteria attached to reimbursement approval for new medicines. Health technology assessment (HTA) identifies where uncertainty is greatest in relation to clinical and cost-effectiveness evidence and budget impact estimates; our health technology management (HTM) approach uses these outputs from HTA to design protocols to manage these uncertainties in the post-reimbursement phase.

A bespoke managed access protocol (MAP) is developed for each medicine reimbursed under this approach, informed by uncertainties highlighted in the HTA, directions from the decision-maker, and relevant particulars arising from commercial negotiations. Individual patient reimbursement applications are submitted via an online application system linked directly to the national pharmacy claims system. Pharmacists review the applications and approve reimbursement support where the patient meets the reimbursement criteria. The process is adaptive, allowing expansion of the criteria to include previously excluded patient cohorts, and the addition of new indications. It can also work across differing reimbursement arrangements (hospital/primary care).

The MAP for liraglutide for weight management confines reimbursement to patients with a body mass index greater than or equal to 35 kg/m², prediabetes, and high risk for cardiovascular disease. Phase I reimbursement support lasts for six months; patients not attaining greater than or equal to five percent weight loss are deemed non-responders as per the HTA, and reimbursement support is discontinued. The MAP for dupilumab confined reimbursement support to adults with refractory moderate-to-severe atopic dermatitis, where cost-effectiveness was plausible in the HTA. The MAP for calcitonin-gene-related-peptides monoclonal antibodies confines reimbursement support to patients with chronic migraine, refractory to at least three prophylactic treatments, where cost-effectiveness was plausible in the HTA.

Across these MAPs, over 3,000 patients accessed novel treatments for chronic illnesses in September 2023. HTM provides an effective mechanism to facilitate access to high-cost medicines for targeted patient groups, while providing increased oversight and budgetary certainty. Key to acceptance is utilization of HTA outputs to implement evidence-based HTM measures targeting specific uncertainties as highlighted in the HTA report.

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M.

Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12 months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests.

Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively.

Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Society of Thoracic Surgeons Congenital Heart Surgery Database is the largest congenital heart surgery database worldwide but does not provide information beyond primary episode of care. Linkage to hospital electronic health records would capture complications and comorbidities along with long-term outcomes for patients with CHD surgeries. The current study explores linkage success between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health record data in North Carolina and Georgia.

The Society of Thoracic Surgeons Congenital Heart Surgery Database was linked to hospital electronic health records from four North Carolina congenital heart surgery using indirect identifiers like date of birth, sex, admission, and discharge dates, from 2008 to 2013. Indirect linkage was performed at the admissions level and compared to two other linkages using a “direct identifier,” medical record number: (1) linkage between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health records from a subset of patients from one North Carolina institution and (2) linkage between Society of Thoracic Surgeons data from two Georgia facilities and Georgia’s CHD repository, which also uses direct identifiers for linkage.

Indirect identifiers successfully linked 79% (3692/4685) of Society of Thoracic Surgeons Congenital Heart Surgery Database admissions across four North Carolina hospitals. Direct linkage techniques successfully matched Society of Thoracic Surgeons Congenital Heart Surgery Database to 90.2% of electronic health records from the North Carolina subsample. Linkage between Society of Thoracic Surgeons and Georgia’s CHD repository was 99.5% (7,544/7,585).

Linkage methodology was successfully demonstrated between surgical data and hospital-based electronic health records in North Carolina and Georgia, uniting granular procedural details with clinical, developmental, and economic data. Indirect identifiers linked most patients, consistent with similar linkages in adult populations. Future directions include applying these linkage techniques with other data sources and exploring long-term outcomes in linked populations.

Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI. We hypothesized that a substantial proportion of individuals would display trajectories distinct from the group-average course, with some exhibiting less favorable courses.

Participants were level 1 trauma center patients with TBI (n = 1943), orthopedic trauma controls (n = 257), and non-injured friend controls (n = 300). Trajectories of six symptom dimensions (Depression, Anxiety, Fear, Sleep, Physical, and Pain) were identified using growth mixture modeling from 2 weeks to 12 months post-injury.

Depression, Anxiety, Fear, and Physical symptoms displayed three trajectories: Stable-Low (86.2–88.6%), Worsening (5.6–10.9%), and Improving (2.6–6.4%). Among symptomatic trajectories (Worsening, Improving), lower-severity TBI was associated with higher prevalence of elevated symptoms at 2 weeks that steadily resolved over 12 months compared to all other groups, whereas higher-severity TBI was associated with higher prevalence of symptoms that gradually worsened from 3–12 months. Sleep and Pain displayed more variable recovery courses, and the most common trajectory entailed an average level of problems that remained stable over time (Stable-Average; 46.7–82.6%). Symptomatic Sleep and Pain trajectories (Stable-Average, Improving) were more common in traumatically injured groups.

Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization.

Serial cross-sectional study.

Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU.

Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models.

We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80–0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89–0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91–1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84–1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed.

On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.

Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).

Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.

All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).

Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.

To explore the perspectives, barriers and enablers on salt reduction in out-of-home sectors in Malaysia among street food vendors, caterers and consumers.

A qualitative study involving twenty-two focus group discussions and six in-depth interviews was conducted, recorded and transcribed verbatim. An inductive thematic analysis approach was employed to analyse the data.

Two in-depth interviews and twenty-two focus group discussions were conducted face-to-face. Four in-depth interviews were conducted online.

Focus group discussions were conducted among twenty-three street food vendors, twenty-one caterers and seventy-six consumers of various eateries. In-depth interviews were conducted among two street food vendors and four caterers, individually.

Consumers and food operators perceived a high-salt intake within Malaysia’s out-of-home food sectors. Food operators emphasised the necessity for a comprehensive salt reduction policy in the out-of-home sector involving all stakeholders. Consumers faced limited awareness and knowledge, counterproductive practices among food operators and challenges in accessing affordable low-Na food products, whereas food operators faced the lack of standardised guidelines and effective enforcement mechanisms and uncooperative consumer practices. Both groups expressed that food quality and price of salt were also the barriers, and they advocated for awareness promotion, enhanced regulation of manufactured food products and stricter enforcement targeting vendors. Consumers also suggested promoting and recognising health-conscious food premises, whereas food operators suggested on knowledge enhancement tailored to them, strategies for gaining consumers acceptance and maintaining food quality.

These findings provide valuable insights that serve as foundational evidence for developing and implementing salt reduction policies within Malaysia’s out-of-home sectors.

Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.

We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.

Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.

Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.