Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention.

BACKGROUND: The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. METHODS: Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. RESULTS: Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. CONCLUSION: In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

A nationwide cohort study comparing the effectiveness of diuretics and calcium channel blockers on top of renin-angiotensin system inhibitors on chronic kidney disease progression and mortality.

It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m2), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. We identified 5875 patients (median age 71 years, 64% men, median eGFR 26 ml/min per 1.73m2), of whom 3165 started a diuretic and 2710 a CCB. After a median follow-up of 6.3 years, 2558 MAKE, 1178 MACE and 2299 deaths occurred. Compared to CCB, diuretic use was associated with a lower risk of MAKE (weighted hazard ratio 0.87 [95% confidence interval: 0.77-0.97]), consistent across single components (KRT: 0.77 [0.66-0.88], over 40% eGFR decline: 0.80 [0.71-0.91] and eGFR under 15ml/min/1.73m2: 0.84 [0.74-0.96]). The risks of MACE (1.14 [0.96-1.36]) and all-cause mortality (1.07 [0.94-1.23]) did not differ between therapies. Results were consistent when modeling the total time drug exposure, across sub-groups and a broad range of sensitivity analyses. Thus, our observational study suggests that in patients with advanced CKD, using a diuretic rather than a CCB on top of RASi may improve kidney outcomes without compromising cardioprotection.

Poor recognition and undertreatment of anemia in patients with chronic kidney disease managed in primary care.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD), but limited awareness and treatment options may hinder its management among CKD patients followed in primary care. METHODS: We evaluated adults with CKD stages 3-5 attending primary care in Stockholm, Sweden, 2012-2018. We assessed the incidence of anemia, clinical reactions, and association with subsequent major adverse cardiovascular events (MACE) and death. RESULTS: We identified 45,637 patients with CKD stages 3-5 free from anemia (mean age 78 years; 64% females; 79% CKD stage 3b). During a median follow-up of 2.4 years, 26% of patients developed anemia, and 10.4% developed severe anemia (hemoglobin <10 g/dL). Within 6 months from the anemia event, iron tests were infrequent; ferritin and transferrin saturation were tested in 27% and 11% of anemia cases, respectively, and 49% and 24% of severe anemia cases. Few patients were recognized with a clinical diagnosis (15% of anemia cases; 68% of severe anemias). Only 19% of patients with anemia received treatment, primarily iron (10%) and blood transfusions (7%); erythropoietin-stimulating agent use was anecdotal (∼1%). Treatment rates for severe anemia were higher, but 43% of patients still failed to receive treatment. Developing anemia was associated with a higher risk of MACE and death. CONCLUSION: Anemia was common and associated with adverse outcomes among patients with CKD stages 3-5 managed in primary care. Iron stores were infrequently tested, and a large proportion of patients with anemia remained untreated/under-recognized.

Psoriasis/Psoriatic Arthritis Patients' Long-term Treatment Patterns and Adherence to Systemic Treatments Monitoring Recommendations.

Limited information exists regarding treatment of patients with psoriasis/psoriatic arthritis in primary care. The aim of this study is to assess treatment patterns, adherence, persistence, and compliance in newly diagnosed patients with psoriasis/psoriatic arthritis from 2012 to 2018 in Stockholm, Sweden. In addition, laboratory monitoring before initiation of treatment and at recommended intervals was quantified for patients prescribed methotrexate or biologics. A total of 51,639 individuals were included, with 39% initiating treatment with topical corticosteroids and < 5% receiving systemic treatment within 6 months post-diagnosis. During a median (interquartile range) follow-up of 7 (4-8) years, 18% of patients received systemic treatments at some point. Overall, 5-year persistence rates were 32%, 45% and 19% for methotrexate, biologics, and other systemic treatments, respectively. Pre-initiation laboratory tests, as recommended by guidelines, were performed in approximately 70% and 62% of methotrexate and biologics users, respectively. Follow-up monitoring at recommended time intervals occurred in 14-20% and 31-33% of patients prescribed methotrexate and biologics, respectively. These findings highlight gaps in the pharmacological care of patients with psoriasis/psoriatic arthritis, including suboptimal adherence/persistence and inadequate laboratory monitoring.

GLP-1 receptor agonist versus DPP-4 inhibitor and kidney and cardiovascular outcomes in clinical practice in type-2 diabetes.

Whether glucagon-like peptide-1 receptor agonists (GLP1-RA) reduce detrimental kidney outcomes is uncertain. In secondary analyses, trials have shown consistent reductions in macroalbuminuria, but inconclusive results about kidney function decline. To help clarify this, we conducted a cohort study to compare kidney and cardiovascular outcomes in individuals who started GLP1-RA or dipeptidyl peptidase-4 inhibitors (DPP4i) (reduces degradation of endogenous GLP1). The primary outcome was a composite of sustained doubling of creatinine, kidney failure or kidney death. The secondary outcomes were three-point major adverse cardiovascular events (MACE) and its individual components. Propensity score weighted Cox regression was used to balance 53 confounders. A total of 19,766 individuals were included, of whom 5,699 initiated GLP1-RA, and were followed for a median 2.9 years. Mean age was 63 years, 26.2% had atherosclerotic cardiovascular disease and 16.0% had an estimated glomerular filtration rate (eGFR) under 60 ml/min/1.73m2. The adjusted hazard ratio for GLP1-RA vs. DPP4i was 0.72 (95% confidence interval 0.53-0.98) for the composite kidney outcome and 0.85 (0.73-0.99) for MACE, with absolute five-year risk reductions of 0.8% (0.1%-1.5%) and 1.6% (0.2%-2.9%), respectively. Hazard ratios were 0.79 (0.60-1.05) for cardiovascular death, 0.86 (0.68-1.09) for myocardial infarction and 0.74 (0.59-0.93) for stroke. Results were consistent within subgroups, including age, sex, eGFR and baseline metformin use. Thus, in our analysis of patients from routine clinical practice, the use of GLP1-RA was associated with a lower risk of kidney outcomes compared with DPP4i. Reductions in both kidney outcomes and MACE were similar in magnitude to those reported in large cardiovascular outcome trials.

Lipid-lowering treatment intensity, persistence, adherence and goal attainment in patients with coronary heart disease.

BACKGROUND: To examine patterns of lipid-lowering therapy (LLT) use, and persistence and adherence among patients with coronary heart disease and their associations with lipoprotein cholesterol (LDL-C) goal attainment. METHODS: Observational study among 26,768 patients who had suffered a myocardial infarction or had been revascularized in Stockholm during 2012 to 2018, and followed up through 2019. Outcomes included initiation of LLT, discontinuation, re-initiation, adherence to treatment and LDL-C goal attainment according to the European dyslipidaemia guidelines from 2011 and 2016 (mainly LDL-C <1.8 mmol/L). RESULTS: 82% of patients commenced or continued LLT within 90 days after discharge. Of those, 71% were dispensed an LLT prescription within 30 days (62% of them for high-intensity LLT). High-intensity LLT prescribing increased over time, from 12% in 2012 to 78% in 2018. During a median follow-up of 3 (IQR 2-5) years 73% continued to fill prescriptions for a statin, 26.3% temporarily or permanently discontinued, and 0.5% changed to non-statin LLT. Only 1.3% discontinued statin treatment permanently. Throughout observation, about 80% of patients showed good statin adherence (proportion of days covered ≥80%). LDL-C target attainment was 52% the first year and <50% during subsequent years. LDL-C goal attainment was highest among patients receiving high-intensity statin treatment and showing good treatment adherence. CONCLUSION: In secondary prevention for patients with established coronary heart disease, the proportion of LDL-C target attainment was low throughout the time period of the study, despite increasing use of high-intensity LLT and good treatment persistence and adherence.

Hyponatremia Following Antipsychotic Treatment: In Silico Pharmacodynamics Analysis of Spontaneous Reports From the US Food and Drug Administration Adverse Event Reporting System Database and an Updated Systematic Review.

BACKGROUND: Hyponatremia associated with antipsychotic drugs is a rare but potentially life-threatening adverse drug reaction; the underlying pharmacological mechanism has not yet been explained. METHODS: We investigated the relationship between pharmacological targets of antipsychotic drugs and the occurrence of hyponatremia by conducting a nested case-control study using the Food and Drug Administration Adverse Event Reporting System database. Multiple logistic regression was used to determine the associations between antipsychotics receptor occupancy and hyponatremia. We also performed a systematic review of clinical studies on this association. RESULTS: Of 139 816 reports involving at least 1 antipsychotic, 1.1% reported hyponatremia. Olanzapine was the most frequently suspected drug (27%). A significant positive association was found between dopamine D3, D4, and hyponatremia, while adrenergic α 1, serotonin 5-HT1A, and 5-HT2A receptor occupancies were negatively associated. A multivariable stepwise regression model showed that dopamine D3 (adj. odds ratio = 1.21; 95% CI = 1.09-1.34; P < .05) predicted the risk for hyponatremia (P < .05), while serotonin 5-HT2A occupancy (Adj. odds ratio = 0.78; 95% CI = 0.68-0.90; P < .01) exhibited a protective effect against hyponatremia. Among the 11 studies included in the systematic review, incidence rates of hyponatremia diverged between 0.003% and 86%, whereas the odds of developing hyponatremia from effect studies ranged between 0.83 and 3.47. CONCLUSIONS: Antipsychotic drugs having a combined modest occupancy for D3 and 5-HT2A receptors and higher levels of D3 receptor occupancy correspond to different degrees of risk for hyponatremia. Based on the few, relatively large-scale available studies, atypical antipsychotics have a more attenuated risk profile for hyponatremia.

Association between the glyco-metabolic adverse effects of antipsychotic drugs and their chemical and pharmacological profile: a network meta-analysis and regression.

BACKGROUND: Glyco-metabolic deteriorations are the most limiting adverse reactions to antipsychotics in the long term. They have been incompletely investigated and the properties of antipsychotics that determine their magnitude are not clarified.To rank antipsychotics by the magnitude of glyco-metabolic alterations and to associate it to their pharmacological and chemical properties, we conducted a network meta-analysis. METHODS: We searched PubMed, Embase, and Psycinfo on 10 September 2020. We selected studies containing the endpoint-baseline difference or the distinct values of at least one outcome among glucose, HbA1c, insulin, HOMA-IR, triglycerides, total/HDL/LDL cholesterols. Of 2094 articles, 46 were included in network meta-analysis. Study quality was assessed by the RoB 2 and ROBINS-I tools. Mean differences (MD) were obtained by random-effects network meta-analysis; relations between MD and antipsychotic properties were analyzed by linear regressions. Antipsychotic properties investigated were acidic and basic pKa, polar surface area, polarizability, and occupancies of D2, H1, M1, M3, α1A, α2A, 5-HT1A, 5-HT2A, 5-HT2C receptors. RESULTS: We meta-analyzed 46 studies (11 464 patients); on average, studies lasted 15.47 weeks, patients had between 17.68 and 61.06 years of mean age and 61.64% were males. Olanzapine and clozapine associated with greater deteriorations, aripiprazole and ziprasidone with smaller deteriorations. Higher polarizability and 5-HT1A receptor occupancy were associated with smaller deteriorations, H1, M1, and M3 receptor occupancies with larger deteriorations. CONCLUSIONS: Drug rankings may guide antipsychotic switching toward metabolically safer drugs. Mechanistic insights may suggest improvements for combination therapies and drug development. More data are required regarding newer antipsychotics.

Finding Early Improvement Threshold to Predict Response After 8 Weeks of Treatment Using Risperidone in First-Episode Psychosis.

PURPOSE/BACKGROUND: The study aims to assess whether the early response can predict the outcome at the endpoint for the treatment of first-episode psychosis with risperidone and identify the relationship between initial symptom reduction and late response. METHODS/PROCEDURES: A prospective observational study with 4 points follow-up (weeks 2, 3, 4, and 8) was conducted in 48 adult first-episode psychosis patients. Symptoms were quantified by the Positive and Negative Syndrome Scale (PANSS) score. The initial recommended dose was 2 mg of risperidone once daily before sleep. The PANSS score on day 1 (before initiation of drug therapy) was considered as the baseline score. Treatment responses were considered as a reduction of more than 20%, 25%, 30% and 50% from the baseline score on first, second, third, and final follow-up, respectively. Receiver operating characteristic curves were generated for predicting response at the endpoint. FINDINGS/RESULTS: Thirty-one (65%) patients achieved more than 50% reduction (responders) in PANSS score. The mean total PANSS score of the study population after 8 weeks of therapy was found to be 49.77 (95% confidence interval, 46.10-53.43). The mean percentage reduction in PANSS score after 8 weeks of therapy was found to be 52.92% (95% confidence interval, 48.83-57.01). Week 2 response can be taken as the early response (area under the curve = 81.9, P < 0.001). However, the more accurate prediction was possible with week 4 response (area under the curve = 88.7%, P < 0.001). IMPLICATIONS/CONCLUSIONS: Our study suggests that patients with an early response at week 2 are likely to achieve positive response after 8 weeks.

Beta-blocker-associated hypoglycaemia: New insights from a real-world pharmacovigilance study.

AIMS: To investigate the statistical association between hypoglycaemia and ß-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence. METHODS: We investigated the relationship between pharmacological parameters of ß-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association. RESULTS: Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for ß1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20). CONCLUSION: Nadolol appears to be the ß-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective ß-blockers seem to increase the risk for its occurrence.

Health-related quality of life and its predictors among adults living with HIV/AIDS and receiving antiretroviral therapy in Pakistan.

BACKGROUND: Health-related quality of life (HRQoL) is considered to be the fourth 90 of UNAIDS 90-90-90 target to monitor the effects of combination antiretroviral therapy (ART). ART has significantly increased the life expectancy of people living with HIV/AIDS (PLWHA). However, the impact of chronic infection on HRQoL remains unclear, while factors influencing the HRQoL may vary from one country to another. The current study aimed to assess HRQoL and its associated factors among PLWHA receiving ART in Pakistan. METHODS: A cross-sectional descriptive study was conducted among PLWHA attending an ART centre of a tertiary care hospital in Islamabad, Pakistan. HRQoL was assessed using a validated Urdu version of EuroQol 5 dimensions 3 level (EQ-5D-3L) and its Visual Analogue Scale (EQ-VAS). RESULTS: Of the 602 patients included in the analyses, 59.5% (n = 358) reported no impairment in self-care, while 63.1% (n = 380) were extremely anxious/depressed. The overall mean EQ-5D utility score and visual analogue scale (EQ-VAS) score were 0.388 (SD: 0.41) and 66.20 (SD: 17.22), respectively. Multivariate linear regression analysis revealed that the factors significantly associated with HRQoL were: female gender; age  > 50 years; having primary and secondary education;  > 1 year since HIV diagnosis; HIV serostatus AIDS-converted; higher CD 4 T lymphocytes count; detectable viral load; and increased time to ART. CONCLUSIONS: The current findings have shown that PLWHA in Pakistan adherent to ART had a good overall HRQoL, though with significantly higher depression. Some of the factors identified are amenable to institution-based interventions while mitigating depression to enhance the HRQoL of PLWHA in Pakistan. The HRQoL determined in this study could be useful for future economic evaluation studies for ART and in designing future interventions.

Potentially inappropriate medications use and its association with health-related quality of life among elderly cardiac patients.

BACKGROUND: Previous studies identified alarming use of potentially inappropriate medications (PIMs) in Pakistani population but its effect on health-related quality of life (HRQoL) is still largely unknown. OBJECTIVE: This study aimed to determine the association between PIMs use and HRQoL among elderly cardiac outpatients. METHOD: A descriptive, non-experimental, cross-sectional study was carried out from June 2018 to September 2018 in two outpatient departments of tertiary-care hospitals in the Punjab Province of Pakistan. The population under study were patients aged ≥ 65 years with at least one cardiovascular condition taking at ≥ 1 prescribed medication. Patients with PIMs were identified by using Beers criteria. HRQoL was assessed using EuroQoL-5 dimension (EQ-5D) and EuroQoL-visual analogue scale (EQ-VAS). The association of PIMs with HRQoL was analyzed using χ2 tests, independent sample t-test, and one-way ANOVA tests. Multiple linear regression analysis was used to determine how HRQoL varied by PIMs use after adjusting for patient-level covariates. RESULTS: Of 386 elderly cardiac patients, 260 (67.4%) patients were receiving at least one PIM. Mean EQ-5D scores were significantly lower among patients with PIMs (0.51) compared to patients without PIMs (0.65) (P < 0.001). In multiple linear regression analysis, increasing numbers of PIMs were significantly associated with lower EQ-5D scores [ß = - 0.040 (- 0.075, - 0.005), P < 0.001] and VAS scores [ß = - 1.686 (- 2.916, - 0.456), P < 0.05]. CONCLUSION: The present study concluded that exposure to PIM was significantly associated with lower HRQoL. This indicates that guidelines recommendations should be followed to improve patient's quality of life.

Adverse Drug Reactions Related to Mood and Emotion in Pediatric Patients Treated for Attention Deficit/Hyperactivity Disorder: A Comparative Analysis of the US Food and Drug Administration Adverse Event Reporting System Database.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) can be comorbid with frequent anxiety and mood disorders, as well as emotional symptoms (anxiety, irritability, mood lability). These may also be triggered by drugs and appear as adverse drug reactions (ADRs). METHODS: We mined data from the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database, focused on methylphenidate, atomoxetine, amphetamine, lisdexamfetamine, and their derivatives. We collected reports of ADRs connected with mood or emotional symptoms in pediatric patients, excluding drug abuse/accidents. Reporting odds ratios (RORs) were calculated and compared between drug classes and children/adolescents. RESULTS: We collected 6176 ADRs of interest of which 59% occurred in children. Atomoxetine accounted for 50.7% of reports, methylphenidate for 32.5%, lisdexamfetamine for 14.2%, and amphetamine for 2.6%. Irritability, anxiety, obsessive thoughts, depressed mood, and euphoria scored significant RORs for all drugs, overall with an increasing risk from methylphenidate to atomoxetine, lisdexamfetamine, and amphetamine. Apathy regarded mostly atomoxetine, and crying regarded all drugs except methylphenidate. Several age-based differences were found. Notably, affect lability hit only adolescents. All drugs scored significant self-injury RORs, except lisdexamfetamine in adolescents, with an increasing risk from methylphenidate to lisdexamfetamine, atomoxetine, and amphetamine. For suicidality, all drugs had significant RORs in children, and methylphenidate was better than atomoxetine and lisdexamfetamine. In adolescents, only methylphenidate and atomoxetine scored significant RORs. CONCLUSIONS: We conclude that real-world data from the US Food and Drug Administration Adverse Event Reporting System are consistent with previous evidence from meta-analyses. They support a hierarchy of drug safety for several ADRs (except self-injury/suicidality) with methylphenidate as safest, followed by atomoxetine, lisdexamfetamine, and amphetamine last. Self-injury and suicidality RORs were overall higher in children.

Prospective study of NSAIDs prescribing in Saudi Arabia: Cardiovascular and gastrointestinal risk in patients with diabetes mellitus
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OBJECTIVES: The purpose of this study was to investigate the patterns of nonsteroidal anti-inflammatory drug (NSAID) prescriptions in diabetes mellitus (DM) patients and to evaluate their suitability based on patient gastrointestinal/cardiovascular (GI/CV) risk profiles. MATERIALS AND METHODS: We retrospectively identified patients with DM, who were seen at a primary care facility from March 1 to 31, 2016. GI risk factors, CV histories, and current medications were recorded. Data were evaluated for appropriateness of NSAID prescribing by using current understanding and accepted guidelines. RESULTS: A total of 443 evaluable patients were reviewed. NSAIDs were prescribed in 171 patients (38.5%). Ibuprofen (23.5%) was the most frequently prescribed drug, followed by celecoxib (20%) and naproxen (14.1%). Of 171 patients, 76 (44.4%) had a previous history of CV events, while 52 patients without CV history had a moderate to very high 10-year risk of heart disease. Markedly fewer patients with CV history (19.1%) than patients without CV history were prescribed naproxen. Patients at high GI risk (22.9%) were prescribed traditional NSAIDs without a gastroprotective agent. Overall, 22.9% of patients at high GI risk and 65.8% at high CV risk were prescribed NSAIDs that were not in accordance with current guidelines or recommendations of regulatory agencies. CONCLUSION: Inappropriate prescribing of NSAIDs was found in more than half of the studied DM patients who were at risk for significant GI and CV adverse events. Assessment of GI and CV risks in DM patients is crucial to tailor NSAID selection and optimize patient outcomes.
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A prevalence study of potentially inappropriate medications use in hospitalized Pakistani elderly.

BACKGROUND: Inappropriate prescribing in elderly patients is a widespread health problem. It is associated with increased drug-related problems and health expenditure. AIMS: To determine the prevalence and types of potentially inappropriate medications (PIM) prescribed to elderly patients with polypharmacy and the factors associated with their use in these patients. METHODS: A cross-sectional study conducted among 228 elderly hospitalized patients with polypharmacy. Elderly patients were defined as patients ≥65 years of age, and polypharmacy was defined as taking ≥5 drugs. Based on previously published criteria (Beers and STOPP), a list of 32 PIM was developed using a Delphi technique, which was used as a tool to detect the prevalence of PIM. Age, gender, comorbidity, patients' functional status, and complete medication history were recorded to evaluate as variables related to PIM. The association between PIM used and independent variables was also assessed. RESULTS: The prevalence of PIM used among the hospitalized elderly patients was 64%. PIM use according to STOPP criteria was identified in 44% of patients, whereas Beers-listed PIM were identified in 50% of patients. The most frequently observed PIM were the combination of nonsteroidal anti-inflammatory drugs (NSAIDs) with antihypertensives and long-term NSAIDs, which account for more than 90 and 75% of the total observed PIM, respectively. Patients with age ≥85 years were more likely to be prescribed PIM. High comorbidity was found to be an independent predictor of PIM use. Polypharmacy with ≥10 drugs prescribed to patients predicted the presence of PIM. DISCUSSION: The study showed a high prevalence of PIM use among hospitalized elderly patients. The consensus-validated list of PIM was a useful tool for screening inappropriate prescribing in this particular patient population. CONCLUSION: Our findings support the need for measures to improve the quality of drug treatment in the elderly Pakistani population, especially among dependent patients with polypharmacy.

Occurrence of adverse events associated with the initiation of methotrexate and biologics for the treatment of psoriasis in routine clinical practice.

Background: Limited information exists on the risk of adverse events (AEs) attributed to methotrexate (MTX) and biologics for the treatment of psoriasis/psoriatic arthritis (PsA/PsO) in heterogeneous clinical practice and beyond the duration of clinical trials.Methods: An observational study of 6294 adults with incident PsA/PsO who initiated MTX or biologics in Stockholm from 2006-2021 was conducted. The risk of kidney, liver, hematological, serious infectious, and major gastrointestinal AEs was quantified and compared between therapies using incidence rates, absolute risks, and adjusted hazard ratios (HRs) from propensity-score weighted Cox regression.Results: Median follow-up was 4.3 (2-7) years. Users of MTX had a higher risk of anemia (HR 1.79 [95% CI, 1.48-2.16]), particularly mild-moderate anemias (1.93;1.49-2.50), and mild (1.46;1.03-2.06) and moderate-severe liver AEs (2.22;1.19-4.15) compared to biologics. Chronic kidney disease incidence did not differ between therapies (affecting 1.5% of the population in 5 years; HR:1.03;0.48-2.22). Acute kidney injury, serious infections, and major gastrointestinal AEs showed low absolute risks and no clinically meaningful differences between both therapies.Conclusion: The use of MTX for psoriasis patients in routine care was associated with a higher risk of anemia and liver AEs than biologics, but similar risks of kidney, serious infections, and major gastrointestinal AEs.