Patterns of pain medication usage and self-reported pain in older Irish adults with osteoarthritis: A latent class analysis of data from the Irish Longitudinal Study on Ageing.

BACKGROUND: This study aimed to identify and describe links between pain medication use and self-reported pain among people aged ≥ 50 years with osteoarthritis (OA) in an Irish population, and to examine the relationships between pain, medication usage and socioeconomic and clinical characteristics. METHODS: Secondary data analysis of wave 1 cross-sectional data from The Irish Longitudinal Study on Ageing (TILDA) was undertaken of 1042 people with self-reported doctor-diagnosed OA. We examined use of medications typically included in OA clinical guidelines, including non-opioid analgesics (e.g. paracetamol), topical and oral non-steroidal anti-inflammatory drugs (NSAIDs), opioids and nutraceuticals. Latent Class Analysis (LCA) was used to identify underlying clinical subgroups based on medication usage patterns, and self-reported pain severity. Multinomial logistic regression was used to explore sociodemographic and clinical characteristic links to latent class membership. RESULTS: A total of 358 (34.4%) of the 1042 people in this analysis were taking pain medications including oral NSAIDs (17.5%), analgesics (11.4%) and opioids (8.7%). Nutraceutical (glucosamine/chondroitin) use was reported by 8.6% and topical NSAID use reported by 1.4%. Three latent classes were identified: (1) Low medication use/no pain (n = 382, 37%), (2) low medication use/moderate pain (n = 523, 50%) and (3) moderate medication use/high pain (n = 137, 13%). Poorer self-rated health and greater sleep disturbance were associated with classes 2 and 3; depressive symptoms and female gender were associated with class 2, and retirement associated with class 3. CONCLUSIONS: Whilst pain medication use varied with pain severity, different medication types reported broadly aligned with OA guidelines. The two subgroups exhibiting higher pain levels demonstrated poorer self-rated health and greater sleep disturbance.

Redundancy of Pharmacologic Ingredients in Over-the-Counter Nasal Sprays.

Objective: To evaluate and determine the prevalence of ingredients in over-the-counter (OTC) nasal sprays. Study Design: Cross-sectional. Setting: Retail pharmacies. Methods: An inventory of brand-name and generic OTC nasal sprays was recorded at five national pharmacy outlets in August 2023. Data regarding the active ingredients were collected on commercial websites, MedlinePlus and drugs.com, and frequency statistics were calculated. Results: Five pharmacies were visited, at which 12 different brand names of nasal sprays were identified at multiple pharmacies. Nine brand names were associated with multiple formulations, accounting for 49 different products. The active ingredients included in our analysis were oxymetazoline, phenylephrine, fluticasone, triamcinolone, budesonide, azelastine, cromolyn sodium, and mometasone. Nasal decongestants had the greatest number of brand name formulations compared to intranasal steroids and antihistamine sprays which had limited choices. Products that included oxymetazoline were the most widely marketed drug (51 unique products) followed sodium chloride (40 unique products). Conclusion: These findings suggest that there are widespread redundancies in the OTC nasal spray market. Clinician should be aware of the redundancy in OTC formulations and encourage patients to read the labels in order to make informed decisions regarding their use of OTC medications.

Preventive drug treatments for adults with chronic migraine: a systematic review with economic modelling.

Background: Chronic migraine is a disabling condition, affecting 2-4% of adults globally. With the introduction of expensive calcitonin gene-related peptide monoclonal antibodies, it is timely to compare the clinical effectiveness and cost-effectiveness of preventive drugs for chronic migraine. Objective: To assess the clinical effectiveness and cost-effectiveness of medications used for chronic migraine through systematic reviews and economic modelling. Eligibility criteria: Randomised controlled trials of drug treatments for efficacy with > 100 participants with chronic migraine per arm; for adverse events > 100 participants with episodic or chronic migraine per arm. Previous economic analyses of preventive drugs for chronic migraine. Data sources: Eight databases. Reviews methods: Systematic reviews, network meta-analysis and economic modelling. Outcomes: Monthly headache days, monthly migraine days, headache-related quality of life, cost-effectiveness. Results: We found 51 individual articles, reporting 11 randomised controlled trials, testing 6 drugs (topiramate, Botox, eptinezumab, erenumab, fremanezumab, galcanezumab), versus placebo, on 7352 adults with chronic migraine. Calcitonin gene-related peptide monoclonal antibodies, Botox and topiramate reduced headache/migraine days by 2.0-2.5, just under two, or by less than 1.5 days per month, respectively. In the network meta-analysis, eptinezumab 300 mg and fremanezumab monthly ranked in first place in both monthly headache day and monthly migraine day analyses. The calcitonin gene-related peptide monoclonal antibodies were consistently the best choices for headache/migraine days and headache-related quality of life. Topiramate was very unlikely to be the best choice for headache/migraine days and headache-related quality of life when compared to calcitonin gene-related peptide monoclonal antibodies or Botox. We found no trials of the commonly used drugs, such as propranolol or amitriptyline, to include in the analysis. The adverse events review included 40 randomised controlled trials with 25,891 participants; 3 additional drugs, amitriptyline, atogepant and rimegepant, were included. There were very few serious adverse events - none of which were linked to the use of these medications. Adverse events were common. Most people using some calcitonin gene-related peptide monoclonal antibodies reported injection site issues; and people using topiramate or amitriptyline had nervous system or gastrointestinal issues. The cost-effectiveness review identified 16 studies evaluating chronic migraine medications in adults. The newer, injected drugs are more costly than the oral preventatives, but they were cost-effective. Our economic model showed that topiramate was the least costly option and had the fewest quality-adjusted life-year gains, whereas eptinezumab 300 mg was more costly but generated the most quality-adjusted life-year gains. The cost-effectiveness acceptability frontier showed that topiramate was the most cost-effective medication if the decision maker is willing to pay up to £50,000 per quality-adjusted life-year. Our consensus workshop brought together people with chronic migraine and headache experts. Consensus was reached on the top three recommendations for future research on medications to prevent chronic migraine: (1) calcitonin gene-related peptide monoclonal antibodies and Botox versus calcitonin gene-related peptide monoclonal antibodies, (2) candesartan versus placebo and (3) flunarizine versus placebo. Limitations: Topiramate was the only oral drug for which we were able to include data. We did not find sufficient quality evidence to support the use of other oral drugs. Conclusions: We did not find evidence that the calcitonin gene-related peptide monoclonal antibodies are more clinically and cost-effective when compared to topiramate or Botox. We identified directions for future research these drugs might take. Study registration: This study is registered as PROSPERO CRD42021265990, CRD42021265993 and CRD42021265995. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132803) and is published in full in Health Technology Assessment; Vol. 28, No. 63. See the NIHR Funding and Awards website for further award information.

Chronic migraine is a disabling condition that can destroy work and family life. Treatments include cheap tablets (e.g. amitriptyline, propranolol and topiramate), Botox and expensive new drugs (the calcitonin gene-related peptide monoclonal antibodies). It is not known which of these drugs is the best choice. We wanted to find out which of these drugs works best. We wanted to know if they reduced the number of headache/migraine days and improved headache-related quality of life, how many side effects people experienced, and if they provided good value for the National Health Service. We first looked for research comparing these drugs to placebo (fake) drugs, and to each other. We then worked out which provide best value for money. Calcitonin gene-related peptide monoclonal antibodies reduced headache/migraine days by 2.0­2.5 days per month; Botox reduced headache/migraine days per month by around 1.9; and topiramate reduced headache/migraine days by 1.1­1.5 days per month. Many people taking topiramate or amitriptyline have nervous system and/or stomach/bowel side effects. Some people using calcitonin gene-related peptide monoclonal antibodies reported side effects associated with injections. Some calcitonin gene-related peptide monoclonal antibodies and Botox provide worthwhile benefits on headache-related quality of life. We were not able to identify any studies of sufficient quality to assess the effectiveness of other oral drugs. The best value drug was topiramate which gave better health outcomes at a lower cost than the placebos. After sharing the results with a panel of people with chronic migraine and headache experts, we identified a need for new studies comparing commonly used cheap oral drugs with placebo, Botox and calcitonin gene-related peptide monoclonal antibodies.

Association between prescription drugs and all-cause mortality risk in the UK population.

Although most drugs currently approved are meant to treat specific diseases or symptoms, it has been hypothesized that some might bear a beneficial effect on lifespan in healthy older individuals, outside of their specific disease indication. Such drugs include, among others, metformin, SGLT2 inhibitors and rapamycin. Since 2006, the UK biobank has recorded prescription medication and mortality data for over 500'000 participants, aged between 40 and 70 years old. In this work, we examined the impact of the top 406 prescribed medications on overall mortality rates within the general population of the UK. As expected, most drugs were linked to a shorter lifespan, likely due to the life-limiting nature of the diseases they are prescribed to treat. Importantly, a few drugs were associated with increased lifespans, including notably Sildenafil, Atorvastatin, Naproxen and Estradiol. These retrospective results warrant further investigation in randomized controlled trials.

Danish population based study of familial epilepsy and childhood cancer.

Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95% CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.14, 95% CI = 1.00, 1.30), and central nervous system tumors (CNS) (OR = 1.36, 95% CI = 1.04, 1.76) as well as neuroblastoma (OR = 1.76, 95% CI = 1.06, 2.90) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.99, 95% CI = 0.99, 4.00).

Impact of Socio-Demographics and Knowledge, Attitudes, and Practices (KAP) on Misconceptions of Metformin Use in Diabetes: A Potential Myth and Disbelief in South Asia.

BACKGROUND: The influence of misconceptions and related socio-demographics on metformin use could hamper adherence to medications. This study aimed to assess the rates and causes of metformin non-adherence and to investigate knowledge, attitudes, and practices (KAP) on misconceptions of metformin use including the association with socio-demographic variables. METHODS: An observational analytical cross-sectional study was conducted at the diabetes clinic of Karapitiya Teaching Hospital in Galle, Sri Lanka. Causes of metformin non-adherence, associations with socio-demographics, and KAP on misconceptions on metformin use were assessed using the chi-squared test, t-tests, and ANOVA using IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States) (p<0.05). RESULTS: Metformin non-adherence was reported as 55%. Use of complementary and alternative therapies was 14.7%. Fear of major organ failure was the commonest (20.5%) reason quoted within the non-adherence group (N=223). Socio-demographic factors like ethnicity, lower education, unemployment, use of complementary and alternative therapies, and obtaining medications for other diabetes-related diseases significantly influenced adherence to the metformin-prescribed doses (p<0.05). Among all participants (N=400), the most common misconception was that long-term use of metformin caused organ damage (kidney 72.5%, liver 64.3%, and heart 34.8%), while 44% believed higher doses (two tablets or more for a day) caused organ damage. The KAP scores were reported as 24.5% with low, 52.7% moderate, and 22.7% satisfactory levels. Significantly lower KAP scores were associated with lower education levels and patients obtaining complementary and alternative therapies (p<0.05). CONCLUSION: Misconceptions are not merely kept in mind but lead to non-adherence with metformin doses prescribed and warrant evidence-based educational interventions with the high-risk groups.

Factors Associated With the Use of Over-the-Counter Sleep Aids Among Jazan University Students.

BACKGROUND: Sleep aids, classified by their mechanisms of action, can promote sleep but may be misused, leading to harm. Exercise and pharmacological interventions like antihistamines, melatonin, and benzodiazepines also help manage sleep disorders. In Saudi Arabia, sleep disorders are prevalent, especially among university students. OBJECTIVES: Our study examines the prevalence and usage of the medication containing diphenhydramine hydrochloride, among Jazan University students, aiming to inform better practices and highlight related risks and benefits. METHODS: A cross-sectional design study was conducted among Jazan University students in Saudi Arabia. The sampling of data utilized random selection. Data was cleaned in Excel and analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2023; IBM Corp., Armonk, New York, United States). RESULTS: Our study comprised 437 participants from Jazan University aged 18-25 years. The majority reported earning less than 5000 SAR monthly and were unmarried (91.8%). Remarkably, 13.7% of participants were diagnosed with insomnia. Sleep aid containing diphenhydramine hydrochloride, utilized for mild to moderate pain relief and sleep induction, was the most prevalent medication, with 56.3% of participants having used it and 9.4% using it continuously for over 10 nights. Significant predictors for usage of sleep aids containing diphenhydramine hydrochloride included gender (p=0.041), with male students exhibiting higher usage rates, and college type (p<0.001), particularly medical students. Multivariate analysis confirmed male gender and enrollment in medical colleges as robust predictors. Age, income, marital status, and employment variables showed no significant associations. CONCLUSIONS: Our study highlights a considerable prevalence of sleep aids containing diphenhydramine hydrochloride usage among Jazan University students, notably influenced by gender and college type. Male gender and enrollment in medical colleges emerged as significant predictors of their usage.

The role of perioperative factors in the prognosis of cancer patients: A coin has two sides.

Cancer, the second leading cause of mortality globally, poses a significant health challenge. The conventional treatment for solid tumors involves surgical intervention, followed by chemo- and radio-therapies as well as target therapies, but the recurrence and metastasis of cancers remain a major issue. Anesthesia is essential for ensuring patient comfort and safety during surgical procedures. Despite its crucial role during the surgery, the precise effect of anesthesia on cancer patient outcomes is not clearly understood. This comprehensive review aims to elucidate the various anesthesia strategies used in the perioperative care of cancer patients and their potential effects on patients' prognosis, but understanding the complex relationship between anesthesia and cancer outcomes is crucial, given the complexity in cancer treaments. Examining potential implications of anesthesia strategies on cancer patient prognosis may help better understand treatment efficacy and risk factors of cancer recurrence and metastasis. Through a detailed analysis of anesthesia practices in cancer surgery, this review aims to provide insights that may lead to improving the existing anesthesia protocols and ultimately reduce risk factors for patient outcomes in the field of oncology.

Rate of Breastfeeding Initiation and Continuation in Patients with Epilepsy: Study from a Tertiary Care Center in Makkah.

Objective: The aim of this study was to assess the rate of breastfeeding initiation and continuation among women with epilepsy treated in a tertiary care center in the Makkah region. Methods: All women with epilepsy treated in the epilepsy clinic at King Abdullah Medical City from 2019 to June 2023 were interviewed by phone. Data collected included patients' demographics, type and control of epilepsy, number of antiseizure medications (ASMs), and obstetric history. Results: Forty-eight patients were included in the study. A total of 32 (66.7%) were more than 30 years old, and 41 (85.4%) were from urban areas. A total of 22 (45.8%) received only one antiepileptic drug, 18 (37.5%) received two drugs, and 8 (16.7%) received three or more drugs. The majority (68.6%) of patients practiced breastfeeding. Breastfeeding lasted 6 months or longer for 12.1% of mothers. Bottle feeding was needed for 72.9% of patients. Breastfeeding was reported by significantly more patients (73.2%) from urban areas versus 42.9% of those from rural areas (P = 0.043). Also, 81.8% of patients on one ASM practiced breastfeeding, compared to 62.5% on more than two ASMs (P = 0.048). Other significant factors related to breastfeeding were not having a seizure during pregnancy (81.8%-57.7%, P = 0.049) and a normal vaginal delivery (81.3%-43.8%, P = 0.008). Conclusion: The rate of breastfeeding among women with epilepsy in the Makkah region is low. Several factors, including the number of ASMs, seizure control during pregnancy, spontaneous vaginal delivery, and being from an urban area, were significantly related to breastfeeding behavior among these women.

MADD-like pattern of acylcarnitines associated with sertraline use.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three groups: neonatal onset with congenital anomalies (type 1), neonatal onset without congenital anomalies (type 2), and attenuated and/or later onset (type 3). Here, we present two cases with biochemical profiles mimicking late-onset MADD but negative genetic testing, associated with the use of sertraline, a commonly used antidepressant. Case 1 is a 22 yo woman diagnosed with depression and profound fatigue who was referred to the metabolic clinic because of carnitine deficiency and a plasma acylcarnitine profile with a MADD-like pattern. Case 2 is a 61 yo woman with a history of chronic fatigue who was admitted to the emergency department with difficulty swallowing, metabolic acidosis, and mild rhabdomyolysis. Plasma acylcarnitine profile showed a MADD-like pattern. The muscle biopsy revealed lipid droplet accumulation and proliferation of mitochondria with abnormal osmiophilic inclusions, and a biochemical assay of the respiratory chain showed a deficit in complex II activity. In both cases, urine organic acid profile was normal, and genetic tests did not detect variants in the genes involved in MADD. Sertraline was on their list of medications and considering its association with inhibition of mitochondrial function and rhabdomyolysis, the team recommended the discontinuation under medical supervision. In Case 1 after discontinuation, the plasma acylcarnitine test normalized, only to return abnormal when the patient resumed sertraline. In Case 2, after sertraline was discontinued rhabdomyolysis resolved, and the muscle biopsy and biochemical assay of the respiratory chain normalized. Although sertraline is considered a safe drug, these two cases suggest that the use of sertraline may be associated with a potentially reversible form of mitochondrial dysfunction mimicking MADD. Further studies are needed to confirm and estimate the risk of MADD-like presentations with the use of sertraline, as well as identifying additional contributing factors, including genetic factors. Metabolic physicians should consider sertraline use in the differential diagnosis of MADD, particularly when genetic testing is negative.

Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.

Key HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4+ T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.008). This decline persists for at least 12 weeks following cessation of the study drug. Sirolimus treatment also leads to a significant reduction in CD4+ T cell cycling and PD-1 expression on CD8+ lymphocytes. These data suggest that homeostatic proliferation of infected cells, an important mechanism for HIV persistence, is an intriguing therapeutic target.

The handling of hazardous medications by nurses and midwives: A retrospective cohort study.

BACKGROUND: Occupational exposure of healthcare workers to hazardous medications can be potentially harmful. Hazardous medications can be carcinogenic, developmentally toxic, reproductively toxic, genotoxic and/or toxic to organs at low doses. These hazardous medications can be used in many healthcare settings, but published research of occupational exposure has focused almost exclusively on cancer services. AIM: To identify the healthcare settings where nurses and midwives are responsible for the administration of hazardous medications. METHOD: A retrospective cohort study was undertaken of all medication administration events occurring during a two-week period at a public metropolitan health service in 2023. All medication administration events from six hospital sites were identified using the electronic (Oracle Health-Cerner-Millennium®) and paper (Chemotherapy Chart) medication administration records. From all of the medications administered, the subset of medications classified as hazardous were identified based on the Victorian Therapeutics Advisory Group Framework for Handling of Hazardous Medicines (2021) and other guidelines. Poisson regression modelling was used to explore associations between the number of hazardous medications and the healthcare area where they were administered (p < 0.001). RESULTS: Of the 121,567 administration events, 6054 (5.0 %) involved hazardous medications. The healthcare areas with the highest rate of hazardous medication administration events, as a proportion of all medication administration events, were outpatient cancer service (301/695, 43.3 %), birth suite (13/86, 15.1 %) and mental health (404/4011, 10.1 %) areas. During the two-week period, 6054 hazardous medication administration events occurred, involving 117 different medications. The greatest number of these events took place in the medical (1729/6054, 28.6 %) and geriatric (1579/6054, 26.1 %) inpatient healthcare areas. A total of 1258 nurses and midwives were directly involved in either administering, or checking and witnessing the administration of hazardous medications to 996 patients (25.2 % of the total 3958 patients). Most hazardous medications administered to patients were in an oral dosage form (5426/6054, 89.6 %). CONCLUSION: Hazardous medications were administered in all healthcare areas, with the exception of endoscopy services. Nurses and midwives were at risk of occupational exposure from hazardous medications.

Transition from rectal to intranasal route among mostly pediatric patients with repeated prescriptions of rescue benzodiazepines for seizure emergencies.

OBJECTIVE: To describe the changes in Food and Drug Administration (FDA)-approved non-intravenous rescue benzodiazepine (non-IV-rBZD) use and cost after the introduction of intranasal midazolam and intranasal diazepam. METHODS: Retrospective descriptive study using the MarketScan Database between the years 2016 and 2022. We considered patients who had at least one non-IV-rBZD prescription before the introduction of intranasal rescue medications and at least one non-IV-rBZD prescription after the introduction of intranasal rescue medications. RESULTS: There were 4,444 patients (45.8 % female, median (p25-p75) age of 10.0 (5.0-15.0) years). 2,255 of 4,444 (50.7 %) patients switched from rectal diazepam to either intranasal midazolam (1,110 (25.0 %)) or intranasal diazepam (1,145 (25.8 %)) as their last non-IV-rBZD. The change from rectal to intranasal non-IV-rBZDs has been increasing over the years from 2019 to 2022. On multivariable analysis, having a non-IV-rBZD for epilepsy (rather than for other reasons including febrile seizures), the year of the last rescue medication, urban (non-rural) patient's residence, and certain regions of the United States were the factors most strongly associated with a change from rectal diazepam to intranasal non-IV-rBZDs. After adjusting for inflation, the median (p25-p75) average wholesale price (AWP) of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [702 (406-748) versus 417 (406-426), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [748 (714-755) versus 417 (406-426), Wilcoxon signed rank test p < 0.0001)]. After adjusting for inflation, the median (p25-p75) patient cost of the last non-IV-rBZD was higher than that of the first non-IV-rBZD [16 (3-55) versus 12 (6-31), Wilcoxon signed rank test p < 0.0001)]. This difference was mainly driven by the patients who changed from rectal diazepam to intranasal non-IV-rBZD [41 (6-83) versus 12 (6-30), Wilcoxon signed rank test p < 0.0001)]. CONCLUSION: Approximately half of patients changed from rectal diazepam to intranasal midazolam or intranasal diazepam and that transition has been progressively increasing from the year 2019 to the year 2022. The inflation-adjusted AWP and patient cost increased, especially among those patients who changed from rectal to intranasal rescue medication.

Effect of polypharmacy and potentially inappropriate medications on physical functional decline among older adults with advanced cancer receiving systemic treatment.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIM) are common among older adults with advanced cancer, but their association with physical functional outcomes is understudied. This study aimed to estimate the risk of physical functional decline associated with medication measures in older adults with advanced cancer starting a new line of systemic treatment. METHODS: This secondary analysis of GAP 70+ Trial (PI: Mohile) enrolled patients aged 70+ with advanced cancer, had ≥ 1 geriatric assessment domain impairment and planned to start a new antineoplastic regimen with a high risk of toxicity. Polypharmacy (concurrent use of ≥ 8 medications (meds)) was assessed before initiation of treatment. PIM were categorized using Screening Tool of Older Person's Prescriptions (STOPP) criteria and 2019 Beers criteria. Physical functional outcomes were assessed within 3 months of treatment initiation: (1) Activity of Daily Living (ADL) decline: 1-point decrease in ADL score between baseline and 3 months; (2) Instrumental ADL (IADL) decline: 1-point decrease in IADL score between baseline and 3 months; (3) Short physical performance battery (SPPB) decline, defined as 1-point decrease on SPPB; (4) ≥ 1 falls within 3 months of treatment. Separate multivariable, cluster-weighted Generalized Estimating Equations models adjusted for relevant covariates (e.g., age, baseline function/comorbidities). RESULTS: Among 616 participants, mean number of meds was 6 (range 0-24); 28% received ≥ 8 meds. Polypharmacy was associated with increased risk of ADL decline (adjusted risk ratio [aRR], 1.31; 95% CI, 1.00-1.71). Taking ≥ 1 PIM per STOPP was associated with increased risk of IADL decline (aRR, 1.21; 95% CI, 1.04-1.40) and falls (aRR, 1.93; 95% CI, 1.49-2.51). CONCLUSIONS: In a large cohort of vulnerable older adults with advanced cancer receiving systemic treatment, polypharmacy and PIM were independently associated with an increased risk of physical functional decline. This emphasizes the need to develop interventions to optimize medication use, intending to improve outcomes in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02054741. Registered 01-31-2014.

Community-Based Medications First for Opioid Use Disorder - Care Utilization and Mortality Outcomes.

Purpose: A large treatment gap exists for people who could benefit from medications for opioid use disorder (MOUD). People OUD accessing services in harm reduction and community-based organizations often have difficulty engaging in MOUD at opioid treatment programs and traditional health care settings. We conducted a study to test the impacts of a community-based medications first model of care in six Washington (WA) State communities that provided drop-in MOUD access. Participants and Methods: Participants included people newly prescribed MOUD. Settings included harm reduction and homeless services programs. A prospective cohort analysis tested the impacts of the intervention on MOUD and care utilization. Intervention impacts on mortality were tested via a synthetic comparison group analysis matching on demographics, MOUD history, and geography using WA State agency administrative data. Results: 825 people were enrolled in the study of whom 813 were matched to state records for care utilization and outcomes. Cohort analyses indicated significant increases for days' supply of buprenorphine, months with any MOUD, and months with any buprenorphine for people previously on buprenorphine (all results p<0.05). Months with an emergency department overdose did not change. Months with an inpatient hospital stay increased (p<0.05). The annual death rate in the first year for the intervention group was 0.45% (3 out of 664) versus 2.2% (222 out of 9893) in the comparison group in the 12 months; a relative risk of 0.323 (95% CI 0.11-0.94). Conclusion: Findings indicated a significant increase in MOUD for the intervention group and a lower mortality rate relative to the comparison group. The COVID-19 epidemic and rapid increase in non-pharmaceutical-fentanyl may have lessened the intervention impact as measured in the cohort analysis. Study findings support expanding access to a third model of low barrier MOUD care alongside opioid treatment programs and traditional health care settings.

Correlation between prescription volumes of generic antiepileptic drugs and the number of clinical epileptologists across prefectural regions in Japan: A descriptive study using a national claims database.

PURPOSE: Although generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. METHODS: The number of generic drug prescriptions from 2017-2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population. RESULTS: In 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70-80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = -0.47, p < 0.01). CONCLUSION: Our findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents.

The Dispensing Error Rate in an App-Based, Semaglutide-Supported Weight-Loss Service: A Retrospective Cohort Study.

Digital weight-loss services (DWLSs) combining pharmacotherapy and health coaching have the potential to make a major contribution to the global struggle against obesity. However, the degree to which DWLSs compromise patient safety through the dispensation of Glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications is unknown. This study retrospectively analysed the rate at which patients reported GLP-1 RA dispensing errors from patient-selected and partner pharmacies of Australia's largest DWLS provider over a six-month period. The analysis found that 99 (0.35%) of the 28,165 dispensed semaglutide orders contained an error. Incorrect dose (58.6%) and unreasonable medication expiry window (21.2%) were the two most common error types. Most errors (84.9%) were deemed to have been of medium urgency, with 11.1% being considered high-urgency errors. Incorrect doses (45.5%) and supplies of the wrong medication (36.3%) comprised most errors reported in high-urgency cases. Female patients reported more dispensing errors than male patients (0.41% vs. 0.12%, p < 0.001). Similarly, reported dispensing error rates were highest among patients aged 18 to 29 years (0.6%) and 30 to 39 years (0.5%). This research provides preliminary evidence that GLP-1 RA dispensing errors within comprehensive Australian DWLSs are relatively low.

Infective endocarditis with metastatic infections in a renal transplant recipient: a case report.

BACKGROUND: Infective endocarditis is an uncommon but well-known post-transplant complication with significant morbidity and mortality. It has been observed to be about 171 times more common in solid organ transplant patients than in the general population. With the increasing rate of end-stage kidney disease, the higher demand for kidney transplantation with better graft survival, and life expectancy rates, more transplant recipients may develop infective endocarditis as a late post-transplant complication. Prompt diagnosis of infective endocarditis is therefore necessary to avert graft loss and other life-threatening outcomes. CASE PRESENTATION: We present a case of a 52-year-old African patient who had a live donor kidney transplant 18 months prior to presentation and had been on oral tacrolimus 5 mg every morning/4.5 mg every evening, mycophenolic acid (MPA) 720 mg twice daily, and oral prednisolone 10 mg daily as maintenance immunosuppressive medications. Regarding the above immunosuppressive medications, he had been in good health and had a functioning transplant graft. He presented with a resolving right thigh swelling, recurrence of fever, new onset left hemiplegia, and seizures. Enterococcus faecalis infective endocarditis was diagnosed with metastatic brain abscesses, which was treated with intravenous vancomycin and gentamycin for 5 weeks. There are very few reported cases of infective endocarditis due to Enterococcus faecalis, and this case is unique because the initial presentation was pyomyositis. CONCLUSION: Infective endocarditis with septic embolization to the brain should be considered in kidney transplant recipients with pyomyositis and multiple rim-enhancing lesions, especially in the late post-transplant period with Enterococcal spp. as an emerging cause of infective endocarditis in kidney transplant recipients. Clinicians will need to have a high index of suspicion to aid early diagnosis with appropriate treatment to prevent adverse outcomes.

Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention.

Understanding the molecular mechanisms underlying the generation of absence seizures is crucial for developing effective, patient-specific treatments for childhood absence epilepsy (CAE). Currently, one-third of patients remain refractive to the antiseizure medications (ASMs), previously called antiepileptic drugs (AEDs), available to treat CAE. Additionally, these ASMs often produce serious side effects and can even exacerbate symptoms in some patients. Determining the precise cellular and molecular mechanisms directly responsible for causing this type of epilepsy has proven challenging as they appear to be complex and multifactorial in patients with different genetic backgrounds. Aberrant neuronal activity in CAE may be caused by several mechanisms that are not fully understood. Thus, dissecting the causal factors that could be targeted in the development of precision medicines without side effects remains a high priority and the ultimate goal in this field of epilepsy research. The aim of this review is to highlight our current understanding of potential causative mechanisms for absence seizure generation, based on the latest research using cutting-edge technologies. This information will be important for identifying potential targets for future therapeutic intervention.