Data-Driven Identification of Factors That Influence the Quality of Adverse Event Reports: 15-Year Interpretable Machine Learning and Time-Series Analyses of VigiBase and QUEST.

BACKGROUND: The completeness of adverse event (AE) reports, crucial for assessing putative causal relationships, is measured using the vigiGrade completeness score in VigiBase, the World Health Organization global database of reported potential AEs. Malaysian reports have surpassed the global average score (approximately 0.44), achieving a 5-year average of 0.79 (SD 0.23) as of 2019 and approaching the benchmark for well-documented reports (0.80). However, the contributing factors to this relatively high report completeness score remain unexplored. OBJECTIVE: This study aims to explore the main drivers influencing the completeness of Malaysian AE reports in VigiBase over a 15-year period using vigiGrade. A secondary objective was to understand the strategic measures taken by the Malaysian authorities leading to enhanced report completeness across different time frames. METHODS: We analyzed 132,738 Malaysian reports (2005-2019) recorded in VigiBase up to February 2021 split into historical International Drug Information System (INTDIS; n=63,943, 48.17% in 2005-2016) and newer E2B (n=68,795, 51.83% in 2015-2019) format subsets. For machine learning analyses, we performed a 2-stage feature selection followed by a random forest classifier to identify the top features predicting well-documented reports. We subsequently applied tree Shapley additive explanations to examine the magnitude, prevalence, and direction of feature effects. In addition, we conducted time-series analyses to evaluate chronological trends and potential influences of key interventions on reporting quality. RESULTS: Among the analyzed reports, 42.84% (56,877/132,738) were well documented, with an increase of 65.37% (53,929/82,497) since 2015. Over two-thirds (46,186/68,795, 67.14%) of the Malaysian E2B reports were well documented compared to INTDIS reports at 16.72% (10,691/63,943). For INTDIS reports, higher pharmacovigilance center staffing was the primary feature positively associated with being well documented. In recent E2B reports, the top positive features included reaction abated upon drug dechallenge, reaction onset or drug use duration of <1 week, dosing interval of <1 day, reports from public specialist hospitals, reports by pharmacists, and reaction duration between 1 and 6 days. In contrast, reports from product registration holders and other health care professionals and reactions involving product substitution issues negatively affected the quality of E2B reports. Multifaceted strategies and interventions comprising policy changes, continuity of education, and human resource development laid the groundwork for AE reporting in Malaysia, whereas advancements in technological infrastructure, pharmacovigilance databases, and reporting tools concurred with increases in both the quantity and quality of AE reports. CONCLUSIONS: Through interpretable machine learning and time-series analyses, this study identified key features that positively or negatively influence the completeness of Malaysian AE reports and unveiled how Malaysia has developed its pharmacovigilance capacity via multifaceted strategies and interventions. These findings will guide future work in enhancing pharmacovigilance and public health.

Prothrombin Complex Concentrate vs Conservative Management in ICH Associated With Direct Oral Anticoagulants.

Importance: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) use carries extremely high morbidity and mortality. The clinical effectiveness of hemostatic therapy is unclear. Objective: To compare the clinical and radiological outcomes of DOAC-associated ICH treated with prothrombin complex concentrate (PCC) vs conservative management. Design, Setting, and Participants: In this population-based, propensity score-weighted retrospective cohort study, patients who developed DOAC-associated ICH from January 1, 2016, to December 31, 2021, in Hong Kong were identified. The outcomes of patients who received 25 to 50 IU/kg PCC with those who received no hemostatic agents were compared. Data were analyzed from May 1, 2022, to June 30, 2023. Main Outcomes and Measures: The primary outcome was modified Rankin scale of 0 to 3 or returning to baseline functional status at 3 months. Secondary outcomes were mortality at 90 days, in-hospital mortality, and hematoma expansion. Weighted logistic regression was performed to evaluate the association of PCC with study outcomes. In unweighted logistic regression models, factors associated with good neurological outcome and hematoma expansion in DOAC-associated ICH were identified. Results: A total of 232 patients with DOAC-associated ICH, with a mean (SD) age of 77.2 (9.3) years and 101 (44%) female patients, were included. Among these, 116 (50%) received conservative treatment and 102 (44%) received PCC. Overall, 74 patients (31%) patients had good neurological recovery and 92 (39%) died within 90 days. Median (IQR) baseline hematoma volume was 21.7 mL (3.6-66.1 mL). Compared with conservative management, PCC was not associated with improved neurological recovery (adjusted odds ratio [aOR], 0.62; 95% CI, 0.33-1.16; P = .14), mortality at 90 days (aOR, 1.03; 95% CI, 0.70-1.53; P = .88), in-hospital mortality (aOR, 1.11; 95% CI, 0.69-1.79; P = .66), or reduced hematoma expansion (aOR, 0.94; 95% CI, 0.38-2.31; P = .90). Higher baseline hematoma volume, lower Glasgow coma scale, and intraventricular hemorrhage were associated with lower odds of good neurological outcome but not hematoma expansion. Conclusions and Relevance: In this cohort study, Chinese patients with DOAC-associated ICH had large baseline hematoma volumes and high rates of mortality and functional disability. PCC treatment was not associated with improved functional outcome, hematoma expansion, or mortality. Further studies on novel hemostatic agents as well as neurosurgical and adjunctive medical therapies are needed to identify the best management algorithm for DOAC-associated ICH.

Moment-to-moment affective dynamics in schizophrenia and bipolar disorder.

BACKGROUND: Affective disturbances in schizophrenia and bipolar disorder may represent a transdiagnostic etiological process as well as a target of intervention. Hypotheses on similarities and differences in various parameters of affective dynamics (intensity, successive/acute changes, variability, and reactivity to stress) between the two disorders were tested. METHODS: Experience sampling method was used to assess dynamics of positive and negative affect, 10 times a day over 6 consecutive days. Patients with schizophrenia (n = 46) and patients with bipolar disorder (n = 46) were compared against age-matched healthy controls (n = 46). RESULTS: Compared to controls, the schizophrenia group had significantly more intense momentary negative affect, a lower likelihood of acute changes in positive affect, and reduced within-person variability of positive affect. The bipolar disorder group was not significantly different from either the schizophrenia group or the healthy control group on any affect indexes. Within the schizophrenia group, level of depression was associated with weaker reactivity to stress for negative affect. Within the bipolar disorder group, level of depression was associated with lower positive affect. CONCLUSIONS: Patients with schizophrenia endured a more stable and negative affective state than healthy individuals, and were less likely to be uplifted in response to happenings in daily life. There is little evidence that these affective constructs characterize the psychopathology of bipolar disorder; such investigation may have been limited by the heterogeneity within group. Our findings supported the clinical importance of assessing multiple facets of affective dynamics beyond the mean levels of intensity.

Carbamazepine-Induced Severe Cutaneous Adverse Drug Reactions: A 21-Year Comparison Between Children and Adults in Malaysia.

Severe cutaneous adverse drug reactions (SCARs) are a life-threatening condition. We aimed to identify all carbamazepine-induced SCARs voluntarily reported to the Malaysian pharmacovigilance database and to compare between children and adults. Adverse drug reaction reports for carbamazepine were extracted from 2000 to 2020, and divided into 2 groups, that is, children (aged 0-17 years) and adults (aged 18 years and above). Age, sex, race, and carbamazepine dose were analyzed using multiple logistic regression. Of 1102 carbamazepine adverse drug reaction reports, 416 reports were SCARs (99 children, 317 adults). Stevens-Johnson syndrome and toxic epidermal necrolysis were the main SCAR types for both age groups. Median time-to-onset for any type of SCAR was 13 days, regardless of age. In children, Malay individuals were 3.6 times more likely to report SCARs (95% confidence interval, 1.356-9.546; P = .010) compared to the Chinese population. In adults, carbamazepine-induced SCARs were reported as 3.6 times higher in those with a daily dose of 200 mg or less as compared to a daily dose of 400 mg or more. (95% confidence interval, 2.257-5.758; P < .001) Carbamazepine-induced SCARs reported in Malaysia were predominantly Stevens-Johnson syndrome or toxic epidermal necrolysis, with the majority in Malay individuals. Initiation therapy needs close monitoring between 2 weeks and 1 month.

Injection Site Reactions Before and After Intramuscular Injection Technique Revision: A Postmarketing Analysis of NALDEBAIN® From 2017 to 2022.

BACKGROUND: The NALDEBAIN® has been available since 2017, and high incidence of injection reactions in the phase 3 study has been reported. Since the first year in the market, the injection site reactions were still the majority of adverse drug reactions (ADRs) in pharmacovigilance reports. The new intramuscular (IM) instruction and package was introduced in the middle of 2018. In this retrospective study, we analyzed the pharmacovigilance data and published postmarketing studies to investigate the impact of IM injection-related reactions in Taiwan between the period of 2017-2022. METHODS: Individual case safety reports (ICSRs) and ADRs were classified by system organ class and preferred term. The reporting rate of ICSRs was used to evaluate the impact of the new IM instruction and package. RESULTS: A total of 37 ICSRs were identified from pharmacovigilance reports. Among them, 51% of IM injection-related reactions were reported after one single dose of NALDEBAIN administration. The reporting rate of IM injection-related reactions in pharmacovigilance data dropped from 125.00 to 3.56 per ten thousand exposures after IM instruction and package revision in 2018. In addition, the percentage of IM injection-related reactions also reduced in postmarketing studies from 27.5% to 4.5%. There were no serious IM injection-related reactions found in the pharmacovigilance and postmarketing dataset. CONCLUSION: Injection site reactions were common after intramuscularly administered oil-based agents during the first year which is later markedly reduced by changing the length of the needle and injection education.

Antidepressant use in low- middle- and high-income countries: a World Mental Health Surveys report.

BACKGROUND: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. METHODS: Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents. RESULTS: 3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2-4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness. CONCLUSION: ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Determinants of effective treatment coverage for posttraumatic stress disorder: findings from the World Mental Health Surveys.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with significant morbidity, but efficacious pharmacotherapy and psychotherapy are available. Data from the World Mental Health Surveys were used to investigate extent and predictors of treatment coverage for PTSD in high-income countries (HICs) as well as in low- and middle-income countries (LMICs). METHODS: Seventeen surveys were conducted across 15 countries (9 HICs, 6 LMICs) by the World Health Organization (WHO) World Mental Health Surveys. Of 35,012 respondents, 914 met DSM-IV criteria for 12-month PTSD. Components of treatment coverage analyzed were: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) effective treatment coverage. Regression models investigated predictors of treatment coverage. RESULTS: 12-month PTSD prevalence in trauma exposed individuals was 1.49 (S.E., 0.08). A total of 43.0% (S.E., 2.2) received any mental health services, with fewer receiving adequate pharmacotherapy (13.5%), adequate psychotherapy (17.2%), or effective treatment coverage (14.4%), and with all components of treatment coverage lower in LMICs than HICs. In a multivariable model having insurance (OR = 2.31, 95 CI 1.17, 4.57) and severity of symptoms (OR = .35, 95% CI 0.18, 0.70) were predictive of effective treatment coverage. CONCLUSION: There is a clear need to improve pharmacotherapy and psychotherapy coverage for PTSD, particularly in those with mild symptoms, and especially in LMICs. Universal health care insurance can be expected to increase effective treatment coverage and therefore improve outcomes.

The association between breast arterial calcification and atherosclerotic cardiovascular disease in an Australian population-based breast cancer case-control study.

PURPOSE: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Breast arterial calcification (BAC) on mammograms is not associated with breast cancer risk. However, there is increasing evidence supporting its association with cardiovascular disease (CVD). This study examines the association between BAC and ASCVD and their risk factors within an Australian population-based breast cancer study. MATERIALS AND METHODS: Data from the controls who participated in the breast cancer environment and employment study (BCEES) were linked with the Western Australian Department of Health Hospital Morbidity database and Mortality Registry to obtain ASCVD outcomes and related risk factor data. Mammograms from participants with no prior history of ASCVD were assessed for BAC by a radiologist. Cox proportional hazards regression was used to examine the association between BAC and later occurrence of an ASCVD event. Logistic regression was used to investigate the factors associated with BAC. RESULTS: A total of 1020 women with a mean age of 60 (sd = 7.0 years) were included and BAC found in 184 (18.0%). Eighty (7.8%) of the 1020 participants developed ASCVD, with an average time to event of 6.2 years (sd = 4.6) from baseline. In univariate analysis, participants with BAC were more likely to have an ASCVD event (HR = 1.96 95% CI 1.29-2.99). However, after adjusting for other risk factors, this association attenuated (HR = 1.37 95% CI 0.88-2.14). Increasing age (OR = 1.15, 95% CI 1.12-1.19) and parity (pLRT < 0.001) were associated with BAC. CONCLUSION: BAC is associated with increased ASCVD risk, but this is not independent of cardiovascular risk factors.

Validation of Chinese version of a global anesthetic recovery questionnaire: A multicenter observational trial on ObsQoR-11.

BACKGROUND: The obstetric quality of recovery (ObsQoR-11) is considered one of the best patient-reported outcome measures of post-cesarean recovery. However, it has been neither validated in Chinese nor evaluated at >24 h after delivery. METHODS: Parturients from three hospitals (n = 279) completed the Chinese ObsQoR-11 at 24 h (T1) and 96 h (T2) after elective cesarean delivery. Convergent validity was assessed by correlation of Chinese ObsQoR-11 with a 100-mm numerical rating scale (NRS) of general health status; discriminant validity of good recovery (NRS ≥ 70-mm); and construct validity by correlation with influential factors to post-cesarean recovery. The reliability and responsiveness were also assessed. RESULTS: The Chinese ObsQoR-11 correlated moderately with the NRS [T1: r = 0.38 (95% confidence interval: 0.28-0.48), p < 0.0001; T2: r = 0.43 (95% confidence interval: 0.32-0.52), p < 0.0001] and discriminated between good and poor recovery [T1: mean (SD) score: 64 (20) vs 49 (17), p < 0.0001; T2: median (IQR) score: 81 (66-94) vs. 61 (53-72); p = 0.0002]; weakly correlated with gestational age, successful breastfeeding, and operation time. It was reliable (internal consistency: 0.75 (T1) and 0.82 (T2); split-half: 0.77 (T1) and 0.85 (T2); test-retest intraclass correlation coefficient r > 0.6 for each item) and responsive (Cohen effect size: 0.88; standardized response mean: 0.81). CONCLUSION: The Chinese ObsQoR-11may be used for assessing recovery at 24 h and 96 h after cesarean delivery. However, its' cutoff value for good recovery may be lower than that of other versions.

Development and evaluation of a risk algorithm predicting alcohol dependence after early onset of regular alcohol use.

AIMS: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. DESIGN: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance. SETTING AND PARTICIPANTS: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. MEASUREMENTS: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. FINDINGS: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. CONCLUSIONS: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models.

Multimodal Analgesia With Extended-Release Dinalbuphine Sebacate for Perioperative Management: Expert Opinion and Consensus.

BACKGROUND: The insufficient treatment of postoperative pain is considered a major barrier to enhanced patient recovery following surgery. Opioids remain the standard therapy for postoperative pain; however, the epidemic crisis of opioid abuse in the US has resulted in opioid-sparing multimodal analgesia (MMA) strategies in anesthesia practice. Complete perioperative pain management, particularly after discharge, may be undermined, resulting in chronic postsurgical pain. Thus, anesthesiologists and pain physicians should provide comprehensive MMA guidance for perioperative pain management. METHODS: The Taiwan Pain Society organized a working group, which included experts in the field of anesthesia, pain, and surgery. This group performed an extensive literature search, quality review, and drafted a consensus, which was discussed by experts and edited for feedback. Recommendations covered consent instruction, treatment interventions, intramuscular injection techniques, and prophylaxis for postoperative adverse events. RESULTS: This consensus included (1) a comparison of the pharmacology and pharmacokinetics between nalbuphine and dinalbuphine sebacate, (2) recommendations to help clinicians establish MMA with extended-release dinalbuphine sebacate injection, and (3) management of common adverse events during the perioperative pain period. CONCLUSION: Extended-release dinalbuphine sebacate combined with the MMA strategy can reduce the medical burden and improve the quality of recovery following surgery.

The associations between traumatic experiences and subsequent onset of a substance use disorder: Findings from the World Health Organization World Mental Health surveys.

AIM: Exposure to traumatic events (TEs) is associated with substance use disorders (SUDs). However, most studies focus on a single TE, and are limited to single countries, rather than across countries with variation in economic, social and cultural characteristics. We used cross-national data to examine associations of diverse TEs with SUD onset, and variation in associations over time. METHODS: Data come from World Mental Health surveys across 22 countries. Adults (n = 65,165) retrospectively reported exposure to 29 TEs in six categories: "exposure to organised violence"; "participation in organised violence"; "interpersonal violence"; "sexual-relationship violence"; "other life-threatening events"; and those involving loved ones ("network traumas"). Discrete-time survival analyses were used to examine associations with subsequent first SUD onset. RESULTS: Most (71.0%) reported experiencing at least one TE, with network traumas (38.8%) most common and exposure to organised violence (9.5%) least. One in five (20.3%) had been exposed to sexual-relationship violence and 26.6% to interpersonal violence. Among the TE exposed, lifetime SUD prevalence was 14.5% compared to 5.1% with no trauma exposure. Most TE categories (except organised violence) were associated with increased odds of SUD. Increased odds of SUD were also found following interpersonal violence exposure across all age ranges (ORs from 1.56 to 1.78), and sexual-relationship violence exposure during adulthood (ORs from 1.33 to 1.44), with associations persisting even after >11 years. CONCLUSION: Sexual and interpersonal violence have the most consistent associations with progression to SUD; increased risk remains for many years post-exposure. These need to be considered when working with people exposed to such traumas.

Increased risks for mental disorders among LGB individuals: cross-national evidence from the World Mental Health Surveys.

PURPOSE: Lesbian, gay, and bisexual (LGB) individuals, and LB women specifically, have an increased risk for psychiatric morbidity, theorized to result from stigma-based discrimination. To date, no study has investigated the mental health disparities between LGB and heterosexual AQ1individuals in a large cross-national population-based comparison. The current study addresses this gap by examining differences between LGB and heterosexual participants in 13 cross-national surveys, and by exploring whether these disparities were associated with country-level LGBT acceptance. Since lower social support has been suggested as a mediator of sexual orientation-based differences in psychiatric morbidity, our secondary aim was to examine whether mental health disparities were partially explained by general social support from family and friends. METHODS: Twelve-month prevalence of DSM-IV anxiety, mood, eating, disruptive behavior, and substance disorders was assessed with the WHO Composite International Diagnostic Interview in a general population sample across 13 countries as part of the World Mental Health Surveys. Participants were 46,889 adults (19,887 males; 807 LGB-identified). RESULTS: Male and female LGB participants were more likely to report any 12-month disorder (OR 2.2, p < 0.001 and OR 2.7, p < 0.001, respectively) and most individual disorders than heterosexual participants. We found no evidence for an association between country-level LGBT acceptance and rates of psychiatric morbidity between LGB and heterosexualAQ2 participants. However, among LB women, the increased risk for mental disorders was partially explained by lower general openness with family, although most of the increased risk remained unexplained. CONCLUSION: These results provide cross-national evidence for an association between sexual minority status and psychiatric morbidity, and highlight that for women, but not men, this association was partially mediated by perceived openness with family. Future research into individual-level and cross-national sexual minority stressors is needed.

Risk of serious adverse events after the BNT162b2, CoronaVac, and ChAdOx1 vaccines in Malaysia: A self-controlled case series study.

BACKGROUND: Rapid deployment of COVID-19 vaccines is challenging for safety surveillance, especially on adverse events of special interest (AESIs) that were not identified during the pre-licensure studies. This study evaluated the risk of hospitalisations for predefined diagnoses among the vaccinated population in Malaysia. METHODS: Hospital admissions for selected diagnoses between 1 February 2021 and 30 September 2021 were linked to the national COVID-19 immunisation register. We conducted self-controlled case-series study by identifying individuals who received COVID-19 vaccine and diagnosis of thrombocytopenia, venous thromboembolism, myocardial infarction, myocarditis/pericarditis, arrhythmia, stroke, Bell's Palsy, and convulsion/seizure. The incidence of events was assessed in risk period of 21 days postvaccination relative to the control period. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI) with adjustment for calendar period. RESULTS: There was no increase in the risk for myocarditis/pericarditis, Bell's Palsy, stroke, and myocardial infarction in the 21 days following either dose of BNT162b2, CoronaVac, and ChAdOx1 vaccines. A small increased risk of venous thromboembolism (IRR 1.24; 95% CI 1.02, 1.49), arrhythmia (IRR 1.16, 95% CI 1.07, 1.26), and convulsion/seizure (IRR 1.26; 95% CI 1.07, 1.48) was observed among BNT162b2 recipients. No association between CoronaVac vaccine was found with all events except arrhythmia (IRR 1.15; 95% CI 1.01, 1.30). ChAdOx1 vaccine was associated with an increased risk of thrombocytopenia (IRR 2.67; 95% CI 1.21, 5.89) and venous thromboembolism (IRR 2.22; 95% CI 1.17, 4.21). CONCLUSION: This study shows acceptable safety profiles of COVID-19 vaccines among recipients of BNT162b2, CoronaVac, and ChAdOx1 vaccines. This information can be used together with effectiveness data for risk-benefit analysis of the vaccination program. Further surveillance with more data is required to assess AESIs following COVID-19 vaccination in short- and long-term.

Determinants of effective treatment coverage for major depressive disorder in the WHO World Mental Health Surveys.

BACKGROUND: Most individuals with major depressive disorder (MDD) receive either no care or inadequate care. The aims of this study is to investigate potential determinants of effective treatment coverage. METHODS: In order to examine obstacles to providing or receiving care, the type of care received, and the quality and use of that care in a representative sample of individuals with MDD, we analyzed data from 17 WHO World Mental Health Surveys conducted in 15 countries (9 high-income and 6 low/middle-income). Of 35,012 respondents, 3341 had 12-month MDD. We explored the association of socio-economic and demographic characteristics, insurance, and severity with effective treatment coverage and its components, including type of treatment, adequacy of treatment, dose, and adherence. RESULTS: High level of education (OR = 1.63; 1.19, 2.24), private insurance (OR = 1.62; 1.06, 2.48), and age (30-59yrs; OR = 1.58; 1.21, 2.07) predicted effective treatment coverage for depression in a multivariable logistic regression model. Exploratory bivariate models further indicate that education may follow a dose-response relation; that people with severe depression are more likely to receive any services, but less likely to receive adequate services; and that in low and middle-income countries, private insurance (the only significant predictor) increased the likelihood of receiving effective treatment coverage four times. CONCLUSIONS: In the regression models, specific social determinants predicted effective coverage for major depression. Knowing the factors that determine who does and does not receive treatment contributes to improve our understanding of unmet needs and our ability to develop targeted interventions.

Carnosine Alleviates Knee Osteoarthritis and Promotes Synoviocyte Protection via Activating the Nrf2/HO-1 Signaling Pathway: An In-Vivo and In-Vitro Study.

The most common joint disease in the elderly is knee osteoarthritis (OA). It is distinguished by cartilage degradation, subchondral bone loss, and a decrease in joint space. We studied the effects of carnosine (CA) on knee OA in male Wistar rats. OA is induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) method and in vitro studies are conducted in fibroblast-like synoviocyte cells (FLS). The pain was assessed using weight-bearing and paw-withdrawal tests. CA supplementation significantly reduced pain. The enzyme-linked immunosorbent assay (ELISA) method was used to detect inflammatory proteins in the blood and intra-articular synovial fluid (IASF), and CA reduced the levels of inflammatory proteins. Histopathological studies were performed on knee-tissue samples using toluidine blue and hematoxylin and eosin (H and E) assays. CA treatment improved synovial protection and decreased cartilage degradation while decreasing zonal depth lesions. Furthermore, Western blotting studies revealed that the CA-treated group activated nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase (HO-1) and reduced the expression of cyclooxygenase-2 (COX-2). FLS cells were isolated from the knee joints and treated with IL-1ß to stimulate the inflammatory response and increase reactive oxygen species (ROS). The matrix metalloproteinase protein (MMP's) levels (MMP-3, and MMP-13) were determined using the reverse transcription-polymerase chain reaction (RT-PCR), and CA treatment reduced the MMP's expression levels. When tested using the 2',7'-dicholorodihydrofluroscene diacetate (DCFDA) assay and the 5,5',6,6'-tetracholoro-1,1',3,3'-tertraethylbenzimidazolcarboc janine iodide (JC-1) assay in augmented ROS FLS cells, CA reduced the ROS levels and improved the mitochondrial membrane permeability. This study's investigation suggests that CA significantly alleviates knee OA both in vitro and in vivo.

Sugammadex reversal of muscle relaxant blockade provided less Post-Anesthesia Care Unit adverse effects than neostigmine/glycopyrrolate.

Sugammadex is a direct reversal agent of aminosteroid muscle relaxants, particularly rocuronium, with promptly and completely reverse of deep neuromuscular block (NMB), which allows better surgical conditions. Sugammadex exhibits advantages over indirect reversal agent acetylcholinesterase inhibitor neostigmine with less adverse effects. In this retrospective review, we compared the incidence of postoperative vomiting (POV), postoperative urinary retention (POUR), and hemodynamic changes between sugammadex and neostigmine/glycopyrrolate in reversal of muscular blockade. Sugammadex showed superior in all three aspects. The heart rate was 7.253 lower (P < 0.0001) and mean arterial pressure was 5.213 lower (P < 0.0001) in sugammadex group. The POV of neostigmine/glycopyrrolate group was 3.16 times more than sugammadex group (OR = 3.16, p < 0.0001), and POUR of neostigmine/glycopyrrolate group was 4.291 times more than sugammadex group (OR = 4.291, p < 0.0001). Sugammadex showed better hemodynamic stability, and lower incidence of POV and POUR than neostigmine/glycopyrrolate.

Patterns and correlates of patient-reported helpfulness of treatment for common mental and substance use disorders in the WHO World Mental Health Surveys.

Patient-reported helpfulness of treatment is an important indicator of quality in patient-centered care. We examined its pathways and predictors among respondents to household surveys who reported ever receiving treatment for major depression, generalized anxiety disorder, social phobia, specific phobia, post-traumatic stress disorder, bipolar disorder, or alcohol use disorder. Data came from 30 community epidemiological surveys - 17 in high-income countries (HICs) and 13 in low- and middle-income countries (LMICs) - carried out as part of the World Health Organization (WHO)'s World Mental Health (WMH) Surveys. Respondents were asked whether treatment of each disorder was ever helpful and, if so, the number of professionals seen before receiving helpful treatment. Across all surveys and diagnostic categories, 26.1% of patients (N=10,035) reported being helped by the very first professional they saw. Persisting to a second professional after a first unhelpful treatment brought the cumulative probability of receiving helpful treatment to 51.2%. If patients persisted with up through eight professionals, the cumulative probability rose to 90.6%. However, only an estimated 22.8% of patients would have persisted in seeing these many professionals after repeatedly receiving treatments they considered not helpful. Although the proportion of individuals with disorders who sought treatment was higher and they were more persistent in HICs than LMICs, proportional helpfulness among treated cases was no different between HICs and LMICs. A wide range of predictors of perceived treatment helpfulness were found, some of them consistent across diagnostic categories and others unique to specific disorders. These results provide novel information about patient evaluations of treatment across diagnoses and countries varying in income level, and suggest that a critical issue in improving the quality of care for mental disorders should be fostering persistence in professional help-seeking if earlier treatments are not helpful.

Perceived helpfulness of treatment for social anxiety disorder: findings from the WHO World Mental Health Surveys.

PURPOSE: To investigate the prevalence and predictors of perceived helpfulness of treatment in persons with a history of DSM-IV social anxiety disorder (SAD), using a worldwide population-based sample. METHODS: The World Health Organization World Mental Health Surveys is a coordinated series of community epidemiological surveys of non-institutionalized adults; 27 surveys in 24 countries (16 in high-income; 11 in low/middle-income countries; N = 117,856) included people with a lifetime history of treated SAD. RESULTS: In respondents with lifetime SAD, approximately one in five ever obtained treatment. Among these (n = 1322), cumulative probability of receiving treatment they regarded as helpful after seeing up to seven professionals was 92.2%. However, only 30.2% persisted this long, resulting in 65.1% ever receiving treatment perceived as helpful. Perceiving treatment as helpful was more common in female respondents, those currently married, more highly educated, and treated in non-formal health-care settings. Persistence in seeking treatment for SAD was higher among those with shorter delays in seeking treatment, in those receiving medication from a mental health specialist, and those with more than two lifetime anxiety disorders. CONCLUSIONS: The vast majority of individuals with SAD do not receive any treatment. Among those who do, the probability that people treated for SAD obtain treatment they consider helpful increases considerably if they persisted in help-seeking after earlier unhelpful treatments.

Incidence of Antiseizure Medication-Induced Severe Cutaneous Adverse Reactions in Malaysia.

Antiseizure medication can potentially cause severe cutaneous adverse reactions, and certain antiseizure medication-induced severe cutaneous adverse reactions are associated with specific human leukocyte antigen alleles. This caused a change in antiseizure medication prescribing patterns, which may influence the incidence of antiseizure medication-induced severe cutaneous adverse reactions. Thus, we aimed to determine the incidence of antiseizure medication-induced severe cutaneous adverse reactions and its change over 15 years (2006-2019) in Malaysia. This retrospective analysis combined antiseizure medication-induced SCAR cases from the national adverse drug reaction database in the National Pharmaceutical Regulatory Agency, antiseizure medication usage data from the Malaysian Statistics of Medicine, and prescribing data from University Malaya Medical Centre, a national-level tertiary hospital to calculate antiseizure medication-induced SCAR incidence in Malaysia. We observed an upward trend in reported antiseizure medication-induced SCAR cases from 28 cases in 2006 to 92 in 2016. The incidence of carbamazepine (CBZ)-induced severe cutaneous adverse reactions increased from 7.5 per 1000 person-years (2006) to 17.8 per 1000 person-years (2016) but dropped to 7.2 per 1000 person-years subsequently (2019). Concurrently, there was an increase in the incidence of severe cutaneous adverse reactions secondary to phenytoin and lamotrigine. The prevalent users of CBZ had reduced from 22.8% (2006) to 14.1% (2016), whereas the levetiracetam and sodium valproate users increased by 5.5% and 4.8%, respectively. The incidence of CBZ-induced severe cutaneous adverse reactions had reduced since 2016, probably related to the implementation of human leukocyte antigen-B*1502 screening in Malaysia or substitution of CBZ with other antiseizure medications. However, this was accompanied by an increase in SCAR incidence related to phenytoin and lamotrigine.