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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.

Background: Studies in patients with immune-mediated inflammatory diseases (IMIDs) have inconsistently suggested that anti-TNFα therapy may be associated with excessive weight gain. Research design and methods: We performed a nested case/non-case analysis to investigate the anti-TNF-α inhibitor-associated body-changes in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The risk was expressed as a measure of disproportionality using the reporting odds ratio (ROR) while adjusting for sex, drugs known to cause weight gain and reporter type. We also performed a time-to-onset (TTO) analysis of body weight-related events. Results: Infliximab was the most commonly involved TNF-α inhibitor in body weight-related changes, reaching an aROR of 1.42 (95%CI:1. 26; 1.59). An increased risk was especially found in patients affected by rheumatic disorders, both in the adult and paediatric population. The median TTO after the start of anti- TNFα therapy was about 6-7 months for both children and adults. Conclusions Given the potential effect of these agents on the excess weight gain in IMIDs patients, continuous attention for this side effect with appropriate counselling regarding lifestyle modifications are warranted, especially in those at high risk for obesity.

Background The effectiveness of lipid‐lowering therapy (LLT) is affected by both intensity and adherence. This study evaluated the associations of LLT intensity, adherence, and the combination of these 2 aspects of LLT management with the risk of major adverse cardiovascular events (MACE) in people with coronary heart disease. Methods and Results This is an observational study of all adults who suffered a myocardial infarction or had coronary revascularization during 2012 to 2018 and initiated LLT in Stockholm, Sweden. Study exposures were LLT adherence (proportion of days covered), LLT intensity (expected reduction of low‐density lipoprotein cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity during the previous 12 months were calculated. The primary outcomes were MACE (nonfatal myocardial infarction or stroke and death); secondary outcomes were low‐density lipoprotein cholesterol goal attainment and individual components of MACE. We studied 20 490 patients aged 68±11 years, 75% men, mean follow‐up 2.6±1.1 years. Every 10% increase in 1‐year adherence, intensity, or adherence‐adjusted intensity was associated with a lower risk of MACE (hazard ratio [HR], 0.94 [95% CI, 0.93–0.96]; HR, 0.92 [95% CI, 0.88–0.96]; and HR, 0.91 [95% CI, 0.89–0.94], respectively) and higher odds of attaining low‐density lipoprotein cholesterol goals (odds ratio [OR],1.12 [95% CI, 1.10–1.15]; OR, 1.42 [95% CI, 1.34–1.51], and OR, 1.16 [95% CI, 1.19–1.24], respectively). Among patients with good adherence (≥80%), the risk of MACE was similar with low‐moderate and high‐intensity LLT despite differences in the low‐density lipoprotein cholesterol goal attainment with the treatment intensities. Discontinuation ≥1 year increased the risk markedly (HR,1.66 [95% CI, 1.23–2.22]). Conclusions In routine care, good adherence to LLT was associated with the greatest benefit for patients with coronary heart disease. Strategies that improve adherence and use of intensive therapies could substantially reduce cardiovascular risk.

AIMS To investigate the statistical association between hypoglycaemia and β-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 β-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 β1-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 β-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective β-blockers seem to increase the risk for its occurrence.

BACKGROUND AND AIMS Novel oral anticoagulants (NOAC) are currently the first-line choice for stroke prevention in patients with atrial fibrillation (AF), as they have a better risk/benefit profile compared with vitamin K antagonists (VKA). Secondary analyses of trials suggest that NOAC also reduces kidney outcomes, but this has been less explored. METHOD Observational study from the SCREAM project comparing clinical outcomes of all persons with AF and eGFR ≥15 mL/min/1.73 m2 that initiated NOAC or VKA in Stockholm, Sweden, during 2011–18. The primary outcomes were acute kidney injury (AKI, by diagnosis or sudden creatinine elevation) and the composite of kidney failure and >30% eGFR decline. Secondary outcomes were major bleeding and the composite of hospital admission with stroke or systemic embolism. Inverse probability of treatment weighting (IPTW) was used to balance 51 baseline confounders. Sensitivity analyses included falsification endpoints (pneumonia and cataract surgery), subgroups and evaluation of per-protocol effects. RESULTS A total of 32 699 patients initiated oral anticoagulants (median age, 75 years, 45% women, median eGFR 73 mL/min/1.73 m2), of which 18 323 (56%) used NOAC. Compared with VKA, initiation of NOAC was associated with a 13% lower relative risk of experiencing the composite kidney outcome (HR: 0.87; 95% CI 0.78–0.98) and a 12% relative risk reduction on AKI occurrence (HR: 0.88; 95% CI 0.80–0.97). Compared with VKA, NOAC use was associated with a lower risk of major bleeding (HR 0.77; 95% CI 0.67–0.89), but a similar risk of stroke/systemic embolism (HR: 0.93; 95% CI 0.78–1.11). Results were similar across subgroups, including patients with chronic kidney disease (eGFR CONCLUSION Compared with VKA, and regardless of baseline kidney function, initiation of NOAC was associated with a lower risk of CKD progression, AKI and major bleeding, but a similar risk of the composite of stroke and systemic embolism.

Objectives The acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis is one of the main causes of high mortality in patients with COVID-19 (novel coronavirus disease 2019). We systematically reviewed mortality in COVID-19 patients with ARDS and the potential role of systemic corticosteroids in COVID-19 patients. Methods Electronic databases and country-specific healthcare databases were searched to identify relevant studies/reports. The quality assessment of individual studies was conducted using the Newcastle–Ottawa Scale. Country-specific proportion of individuals with COVID-19 who developed ARDS and reported death were combined in a random-effect meta-analysis to give a pooled mortality estimate of ARDS. Results The overall pooled mortality estimate among 10,815 ARDS cases in COVID-19 patients was 39% (95% CI: 23–56%). The pooled mortality estimate for China was 69% (95% CI: 67–72%). In Europe, the highest mortality estimate among COVID-19 patients with ARDS was reported in Poland (73%; 95% CI: 58–86%) while Germany had the lowest mortality estimate (13%; 95% CI: 2–29%) among COVID-19 patients with ARDS. The median crude mortality rate of COVID-19 patients with reported corticosteroid use was 28.0% (lower quartile: 13.9%; upper quartile: 53.6%). Conclusions The high mortality in COVID-19 associated ARDS necessitates a prompt and aggressive treatment strategy which includes corticosteroids. Most of the studies included no information on the dosing regimen of corticosteroid therapy, however, low-dose corticosteroid therapy or pulse corticosteroid therapy appears to have a beneficial role in the management of severely ill COVID-19 patients.

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. This study aimed to determine the association between PIMs use and HRQoL among elderly cardiac outpatients. 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. 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

Introduction: Anti-Tumor Necrosis Factor-alpha (TNF-α) therapy, primarily infliximab and adalimumab, are now increasingly used to induce and maintain disease remission in the pediatric perianal Cro...

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.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-C1.8 mmol/L).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 and50% during subsequent years. LDL-C goal attainment was highest among patients receiving high-intensity statin treatment and showing good treatment adherence.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.

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 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, use of GLP1-RA was associated with a lower risk of kidney outcomes compared with DPP4i. The reductions in both kidney outcomes and MACE were similar in magnitude to those reported in large cardiovascular outcome trials.

Objectives: To examine the signals of bullous pemphigoid (BP) with dipeptidyl peptidase-4 inhibitors (DPP-4i) in VigiBase® and the potential role of their pharmacodynamic/pharmacokinetic parameters...

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.

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.

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.

The published experience with biologics in childbearing age with autoimmune and inflammatory diseases mainly deals with the use of TNFα inhibitors (TNFα-i). Limited data are available for biologics targeting other cytokines or immunocompetent cells, especially for the inflammasome targeted therapy including IL-1 inhibitors and colchicine. We conducted a nested case-control study by using the US Food and Drug Administration Adverse Event Reporting System database aimed at quantifying the association between the use of IL-1 inhibitors/colchicine in pregnant women and the occurrence of maternal/fetal adverse effects. The reporting odds ratio was used as a measure of disproportional reporting. From the total cohort (40,033 pregnant women), we retrieved 7,620 reports related to neonatal AEs, 2,889 to fetal disorders, 8,364 to abortion, 8,787 to congenital disorders, and 7,937 to labor/delivery complications. Inflammasome-targeted drugs did not present any disproportionate reporting for all these clusters of AEs. TNFα-i confirmed their safety during pregnancy with aROR < 1 for all clusters of AEs except for labor complications. Finally, we performed a systematic review of the current literature. Data from the eligible studies (12 observational studies and 6 case reports; yielding a total of 2,075 patients) were reassuring. We found no major safety issues on malformations risk of inflammasome targeted therapies in pregnancy. However, due to limited data, the routine use of these agents should be considered in pregnancy only if risk benefit assessment justifies the potential risk to the fetus.

Highlights • Clinical trials of HCQ/CQ for COVID-19 had several methodological limitations. • Lack of reporting/adjustment of baseline disease severity confounded trial outcomes. • The trials did not meet the CONSORT criteria in full for reporting harms data. • The trials were associated with a moderate to high risk of bias. • The safety and effectiveness of HCQ/CQ for COVID-19 cannot be established., Objectives We critically evaluated the quality of evidence and quality of harms reporting in clincal trials that recently evaluated the effectiveness of HCQ/CQ in COVID-19. Study Design and Setting Scientific databases were systematically searched to identify relevant trials of HCQ/CQ in COVID-19 published until 10th September, 2020. The Cochrane risk-of-bias tools for randomized trials and non-randomized studies of interventions were used to assess risk of bias of included studies. A 10-item Consolidated Standards of Reporting Trials (CONSORT) harms extension was used to assess for quality of harms reporting. Results Sixteen trials including fourteen randomized and two non-randomized trials met the inclusion criteria. The results from included trials were conflicting, lacked effect estimates adjusted for confounders and baseline disease severity or comorbidities in many cases, and recruited a fairly small cohort of patients. None of the clinical trials met the CONSORT criteria in full for reporting harms data in clinical trials. None of the sixteen trials had an overall ‘low’ risk of bias, while four of the trials had ‘high’, ‘critical’, and ‘serious’ risk of bias. Biases observed in these trials arise from the randomization process, potential deviation from intended interventions, outcome measurement, selective reporting, confounding, participant selection, and/or classification of interventions Conclusion In general, the quality of currently available evidence for the effectiveness of CQ/HCQ in COVID-19 is suboptimal. The importance of a properly designed and reported clinical trial cannot be overemphasized amid the COVID-19 pandemic and its dismissal could lead to poorer clinical and policy decisions resulting in wastage of already stretched invaluable healthcare resources.

Objective: The revised Baux score (age total body surface area (TBSA) burned and inhalation injury)) is predictive of mortality in burn patients. Our study objective was to assess whether the addition of body mass index (BMI) to the revised Baux score would be of value. We posited that increasing BMI follows a pattern similar to age and TBSA in the revised Baux score after severe burn injury. Methods: Patient data from the burn registry was queried for patients admitted between 1/1/2013 to 8/31/2019. Patients 12 years or older with a TBSA of 20% or greater burn were included. Inpatient outcomes were analyzed based on BMI. Results: 56 of 1365 patients met inclusion criteria. Mean age of the study population was 48.25 years and 64.3% of patients were male. Median BMI was 25.8 and median TBSA was 26.5. Inhalation injury was present in 44.6% (25/56) of patients. Median hospital length of stay (LOS) and ICU LOS were 21.5 and 17 days respectively. On bivariate analysis, non-survivors had higher TBSA (41.5% vs 25.5%, p = 0.034), more inhalation injury (83.3%, 10/12 vs 34.8%, 15/43 p = 0.003) and higher complication rates (91.6%, 11/12 vs 59.1 %, 25/43, p = 0.043). Survivors also had higher BMI (28.2 vs 23, p = 0.003) and increased hospital LOS (24 vs 5.5, p = 0.003). Automatic model fit in binary logistic regression showed a negative relationship between BMI and mortality. Conclusion: We found a negative relationship between BMI and mortality. Pre-obesity appears to have a protective role, but BMI was not found to be a useful addition to the revised Baux score. Larger sample sizes may be of benefit a for a for a more definitive understanding of the role of BMI with regards to burn survival.

To characterize adverse reactions associated with medication errors (ME) reported in US Food and Drug Administration Adverse Event Reporting System (US-FAERS), and to identify the potential signals of disproportionate reporting (SDR) for different drugs.ME associated Individual Case Study Report (ICSRs) were identified. ICSRs were categorized by patient age groups, affected stages of medication process and Anatomical Therapeutic Chemical classification system. Disproportionality analyses were performed for different age groups.46,8677 ICSRs were retrieved. An increasing trend in reporting of cases of ME was observed during the studied period. Immunosuppressants and psycholeptic drugs were most frequently involved. Administration errors were reported most frequently, followed by prescribing and dispensing errors. In neonates, SDR following wrong drug administration, wrong dose, and accidental overdose were associated with methylergonovine, zidovudine, and acetaminophen. In elderlies, SDR were found for dose omission and underdose error associated with etanercept and evolocumab.While a detailed root-cause analysis for ME characteristic can rarely be performed on such a dataset, data mining for signals in spontaneous reporting database may assist in identifying potential ME in a more standardized and objective manner. Continued use of spontaneous reporting system for identifying MEs is encouraged to prevent unnecessary patient harm.

BACKGROUND Misoprostol is a synthetic analog of prostaglandin-E1 and it is the most widely used drug for the medical management of incomplete abortion. Acute Coronary Syndrome (ACS) rarely occurs in perimenopausal women, in addition, its presentation is atypical, so the disease is not always recognized. CASE REPORT We describe a case of 39-year-old woman with no major underlying cardiovascular risk factors, who developed an episode of ACS following the administration of two doses of misoprostol. After the discontinuation of misoprostol treatment, there was a complete resolution of patient's symptoms. The case draws attention to a rare side effect of a commonly used drug and alerts the clinicians to be cautious in those patients having baseline risk factors which make the patient more susceptible to such serious adverse drug effect.

Inappropriate prescribing in elderly patients is a widespread health problem. It is associated with increased drug-related problems and health expenditure. 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. 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. 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. 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. 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.

Hyponatraemia induced by antidepressant drugs is a rare but potentially life-threatening adverse reaction. Whether it is associated with all or only some antidepressant drugs is still unclear. This needs to be clarified to guide antidepressant therapies, especially in patients with electrolytic imbalances. The primary objective of this study was to quantify the strength of association between the use of different antidepressant drugs and hyponatraemia by using information reported to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The secondary objective was to investigate the putative relationship between different antidepressant pharmacological targets and the risks of hyponatraemia induced by antidepressant drugs using the ‘pharmacovigilance–pharmacodynamic’ method. We used the FAERS database to conduct a case/non-case analysis on spontaneous reports, focusing on events of hyponatraemia/syndrome of inappropriate antidiuretic hormone secretion (SIADH) reported in connection with the use of antidepressant drugs. Risk was expressed as a measure of disproportionality using the reporting odds ratio while adjusting for sex, age and concomitant medications associated with hyponatraemia/SIADH. We assessed to what extent the receptor-binding properties of antidepressant drugs could associate with the reporting odds ratios of hyponatraemia/SIADH of antidepressant drugs, building a linear regression model that included as independent variables the binding affinities (pKi) to the serotonin transporter, dopamine transporter, norepinephrine transporter, and serotonin 5-HT2C, 5-HT2A and 5-HT1A, and α1- and α2-adrenergic receptors. There were 2233 reports identified. The adjusted reporting odds ratio for the association between antidepressant drug use and hyponatraemia was 1.91 (95% confidence interval 1.83–2.00). The association was strongest for mirtazapine, followed by selective serotonin reuptake inhibitors, and lowest with serotonin-modulating antidepressant drugs. A significant linear correlation was found between the adjusted reporting odds ratios for hyponatraemia and pKi for the adrenergic receptors α1 and α2. Hyponatraemia is reported at a disproportionately higher level with classes of antidepressant drugs (noradrenergic and specific serotonergic antidepressant [mirtazapine] and serotonin modulators [vortioxetine]) that are in general considered to have a better profile of tolerability in terms of hyponatraemia. With regard to the presented results, the risk of hyponatraemia with mirtazapine appears to be greater than what was reported in the literature; however, confounding by indication cannot be ruled out. Our pharmacovigilance–pharmacodynamic analysis also indicates that inhibition of the serotonin transporter may not be involved in the hyponatraemia linked to the use of antidepressant drugs.

The possibility that verapamil has new beneficial effects in diabetic patients in terms of an improvement in glycometabolic control has been put forward recently in several studies. However, to date the issue is still under debate. We conducted the first systematic review examining the impact of verapamil-based treatment on glycometabolic outcomes, in type 2 diabetes (T2D) patients. We searched the PubMed, MEDLINE, Embase, Cochrane and ClinicalTrials.gov up to 9 October 2018, for all studies evaluating whether verapamil-based treatment is associated with changes in glycated haemoglobin (HbA1c), fasting plasma glucose levels, glucose and C-peptide areas from baseline in humans, without restrictions for study type. Plasma glucose levels were lowered significantly by verapamil-based treatment in patients with T2D (mean change − 13 ± 5.29; P = 0.049); HbA1c values were instead not affected by the drug (mean change − 0.10 ± 0.12; P = 0.453). In five studies, groups exposed to verapamil achieved lower value of glycometabolic outcomes: comparison with values recorded in control groups showed a significant difference, in terms of both HbA1c and plasma glucose levels. Despite the fact that plasma glucose levels were lowered significantly by verapamil-based treatment in patients with T2D (the HbA1c values were not affected by the drug), the clinical significance of the glycometabolic response induced by verapamil-based treatment remains unclear due to the high variety of sample size and type of studies presently available. Further experimental and clinical trials are needed to clarify unambiguously the role of verapamil in metabolic control.

An increasing amount of preclinical and clinical evidence links together metabolic regulations and psychopathological mechanisms, in particular linking mood disorders with changes in Glycogen Synthase Kinase 3 beta and 5'Adenosine Monophosphate-activated Protein Kinase expression and activity. New hypoglycemic drugs, including thiazolidinediones and glucagon-like peptide 1 (GLP-1) functional agonists, which work by these mechanisms, have also been described as potential antidepressants. The putative role of thiazolidinediones in depression has been already supported, but no clear evidence exists yet for GLP-1 functional agonists. We conducted a systematic review and meta-analysis of the literature to describe the effect of GLP-1 functional agonists on depression rating scales and either support or confute a potential antidepressant role.We searched the PubMed and Scopus databases for terms related to DPP-4 inhibitors and GLP-1 receptor agonists, and depression, including symptoms and rating scales with acronyms and full names. We included longitudinal interventional and observational studies on GLP-1 functional agonists used for depression symptoms. We applied a random effects meta-analysis on standardized mean differences before-after treatment, comparing GLP-1 functional agonists versus control treatments.Literature searches found 815 papers, 8 of which were eligible for meta-analysis. Both control treatments (-0.67, 95%C.I. -0.99 - -0.36, Z = 4.24, p 0.0001) and GLP-1 functional agonists (-1.28, 95%C.I. -2.34 - -0.21, Z = 2.35, p = 0.02) resulted in a significant reduction of depression rating scores, although GLP-1 functional agonists tended to be superior. When a selection was made, including only studies conducted on diabetic patients that did not exclude depressed patients, the effect of GLP-1 functional agonists (-2.09, 95%C.I. -2.28 - -1.91, Z = 22.5, p 0.00001) was significantly superior to that of control treatments (-0.57, 95%C.I. -0.66 - -0.49, Z = 13.6, p 0.00001).Results of this meta-analysis must be carefully considered, since the amount of studies available was low and heterogeneity was high. If further trials will confirm this hypothesis, GLP-1 functional agonists may be considered as antidepressants, either as adjuncts or in mono-therapy, with a peculiar value for preventing the adverse metabolic effects of long-term antipsychotic therapies used in rehabilitation.

Qualitative studies on drug–drug interactions (DDIs) between anticonvulsants and antibiotics report pharmacokinetic changes that may increase the clinical risks in terms of adverse drug reactions (ADRs) and efficacy. However, no studies have provided a systematic and quantitative analysis of anticonvulsant–antibiotic pharmacokinetic DDIs. To provide such indications, we systematically and critically reviewed the literature on anticonvulsant–antibiotic DDIs in terms of quantitative pharmacokinetic changes and related ADRs. We also investigated less-known interactions for the possible occurrence of clinically relevant events. We conducted a systematic review of all reports of DDIs between anticonvulsants and antibiotics assessing pharmacokinetic parameters published until 9 June 2017. We were able to meta-analyse the effect of macrolides on carbamazepine area under the concentration-time curve from time zero to infinity [AUC∞] (+ 34.5 µg/mL*h, p = 0.005, n = 38), clearance (− 2.88 mL/min, p

Background Transition of care on admission to the hospital and between clinical areas are risk points for medication errors. All type of medication errors can be reduced by improving communication at each transition point of care. Objectives This study examines the impact of pharmacist obtained best possible medication histories on medication errors at admission due to unintentional medication discrepancies in older patients. Setting This was a prospective, single-center study conducted in an Internal Medicine Department of a tertiary care teaching hospital in Saudi Arabia. Methods Patients ≥ 65 years with an existing drug therapy on admission were eligible. The best possible medication history taken by the pharmacist from different sources of medication information was compared to the admission medication order to identify and correct unintentional discrepancies. The discrepancies were classified according to the type of errors. An independent multidisciplinary team adjudicated the potential for harm of each type of medication error. Main outcome measure Number and proportion of unintentional medication discrepancies upon admission and associated medication errors. Secondary outcomes included clinical significance and drug classes involved in the discrepancies and risk factors for the occurrence of these discrepancies. Results A total of 375 evaluable patients were identified. Among 375 medication histories, 609 discrepancies were detected of which 226 were recorded as unintentional. 151 patients (42.4%) had ≥ 1 unintended discrepancy. Drug omission (37%) was the most frequent type of error. Nervous system (24.5%), and cardiovascular system (21.2%) were the most common drug classes involved in medication errors. Three-fifths of the UMD had the potential to cause temporary harm with initial or prolonged hospitalization. The number of medications prescribed upon admission (OR 1.32, 95% CI 1.09–1.54, p

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. .

Background: Medication reconciliation is a major component of safe patient care. One of the main problems in the implementation of a medication reconciliation process is the lack of human resources. With limited resources, it is better to target medication reconciliation resources to patients who will derive the most benefit from it. Objective: The primary objective of this study was to determine the frequency and types of medication reconciliation errors identified by pharmacists performing medication reconciliation at admission. Each medication error was rated for its potential to cause patient harm during hospitalization. A secondary objective was to determine risk factors associated with medication reconciliation errors. Methods: This was a prospective, single-center pilot study conducted in the internal medicine and surgical wards of a tertiary care teaching hospital in the Eastern province of Saudi Arabia. A clinical pharmacist took the best possible medication history of patients admitted to medical and surgical services and compared with the medication orders at hospital admission; any identified discrepancies were noted and analyzed for reconciliation errors. Multivariate logistic regression was performed to determine the risk factors related to reconciliation errors. Results: A total of 328 patients (138 in surgical and 198 in medical) were included in the study. For the 1419 medications recorded, 1091 discrepancies were discovered out of which 491 (41.6%) were reconciliation errors. The errors affected 177 patients (54%). The incidence of reconciliation errors in the medical patient group was 25.1% and 32.0% in the surgical group (p

Background:Oxidative stress plays a key role in the pathogenesis of epilepsy and contributes in underlying epileptogenesis process. Anticonvulsant drugs targeting the oxidative stress domain of epileptogenesis may provide better control of seizure. The present study was carried out to investigate the effect of clinically used anti-epileptic drugs (AEDs) on the course of pentylenetetrazole (PTZ)-induced kindling and oxidative stress markers in mice.Methods:Six mechanistically heterogeneous anticonvulsants: phenobarbital, phenytoin, levetiracetam, pregabalin, topiramate, and felbamate were selected and their redox profiles were determined. Diazepam was used as a drug control for comparison. Kindling was induced by repeated injections of a sub-convulsive dose of PTZ (50 mg/kg, s.c.) on alternate days until seizure score 5 was evoked in the control kindled group. Anticonvulsants were administered daily. Following PTZ kindling, oxidative stress biomarkers were assessed in homogenized whole brain samples and estimated for the levels of nitric oxide, peroxide, malondialdehyde, protein carbonyl, reduced glutathione, and activities of nitric oxide synthase and superoxide dismutase.Results:Biochemical analysis revealed a significant increase in the levels of reactive oxygen species with a parallel decrease in endogenous anti-oxidants in PTZ-kindled control animals. Daily treatment with levetiracetam and felbamate significantly decreased the PTZ-induced seizure score as well as the levels of nitric oxide (pConclusions:An AED that produces anticonvulsant effect by the diversified mechanism of action such as levetiracetam, felbamate, and topiramate exhibited superior anti-oxidative stress activity in addition to their anticonvulsant activity.

Dear Sir, Acetaminophen is one of the most commonly used analgesic globally. It is first-line pharmacologic agent for the symptomatic treatment of mild to moderate pain recommended by WHO. Acetaminophen may act as a potent hepatotoxic and it is account for 5% of drug poisonings cases, being a frequent cause of acute liver failure.1 It is still little-known fact that acetaminophen poisoning can cause kidney injury, especially for those pharmacist who are at an early stage of clinical pharmacy career. Therefore this prompt us to provide two interesting cases of acetaminophen poisining with renal manifestions in which clinical pharmacists were active members of the care team. Read more. . .

Spontaneous reporting of adverse drug reactions (ADRs) by health-care professionals is the basic method for the identification and prevention new and serious ADRs of marketed drugs. The contribution of nurses in this task can improve patient safety and reduce the extra financial burden associated with it. Although a total of 11% of ADRs in National Pharmacovigilance and Drug Safety Center were reported by nurses. The objectives of this review were to identify the possible factors that lead to underreporting of ADRs by nurses and define strategies that increase the reporting. This review has revealed various factors that influence the underreporting of ADRs and strategies to encourage reporting by nurses. Most of the identified factors are potentially modifiable. To overcome the underreporting of ADRs by nurses' main interventions should be based on education, motivation, and determination.

Multiple sclerosis is one of several diseases described as demyelinating because it causes damage to the myelin sheath. The presence of additional medical condition like pregnancy, osteoporosis and infections is common with multiple sclerosis that adversely affects the health outcomes. The treatment of MS becomes more complex when compounded by these existing additional medical condition. This review highlight important pharmacotherapeutic considerations in treatment of MS in these special patient population.