Nevin Manimala

Australas J Dermatol. 2021 Dec 27. doi: 10.1111/ajd.13780. Online ahead of print.

ABSTRACT

Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse drug reactions (CADRs). However, there is limited information on the factors associated with these occurrences. In this study, we aimed to describe the demographic, clinical and pharmacological characteristics associated with CADRs encountered by patients administered SSRIs and/or SNRIs for psychiatric diagnoses and to compare the differences in these factors between severe and non-severe CADRs. A protocol was developed a priori (PROSPERO: CRD42020204830) in line with the PRISMA guidelines. We searched PubMed/Medline, PsycINFO and SCOPUS from inception to October 2020 to identify case reports and/or case series of SSRI and SNRI associated CADRs. Additional cases were obtained from the retrieved articles’ bibliography. A total of 141 articles were included in the study, documenting 173 CADRs. Females accounted for 128 (74.0%) of the analysed CADRs. The median age of the cases was 42 IQR (27; 53) with no statistically significant differences in age between males and females (P = 0.542). A total of 157 (90.8%) of the reported CADRs were associated with SSRIs, particularly fluoxetine 68 (39.5%), sertraline 30 (17.4%) and paroxetine 25 (14.5%). Non-severe CADRs and severe CADRs accounted for 23 (13.4%) and 149 (86.6%) reports respectively. No statistically significant differences were observed for gender (P = 0.616), age at onset (P = 0.493) and time to onset (P = 0.105) between non-severe CADRs and SCARs. In conclusion, CADRs following SSRIs and SNRIs disproportionately affect females in the reproductive age group compared to males and are mostly associated with SSRIs.

PMID:34958129 | DOI:10.1111/ajd.13780

Eur J Clin Invest. 2021 Dec 26:e13735. doi: 10.1111/eci.13735. Online ahead of print.

ABSTRACT

BACKGROUND: It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. versus 40 mg o.d. enoxaparin in COVID-19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding.

RESULTS: The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5-11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm.

CONCLUSIONS: No DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

PMID:34958123 | DOI:10.1111/eci.13735

Am J Hypertens. 2021 Dec 27:hpab195. doi: 10.1093/ajh/hpab195. Online ahead of print.

ABSTRACT

BACKGROUND: Targeted treatment of primary aldosteronism (PA) is informed by adrenal vein sampling (AVS), which remains limited to specialized centers. Clinical prediction models have been developed to help select patients who would most likely benefit from AVS. Our aim was to assess the performance of these models for PA subtyping.

METHODS: This external validation study evaluated consecutive patients referred for PA who underwent AVS at a tertiary care referral center in Alberta, Canada during 2006-2018. In alignment with the original study designs and intended uses of the clinical prediction models, the primary outcome was the presence of lateralization on AVS. Model discrimination was evaluated using the C-statistic. Model calibration was assessed by comparing the observed vs. predicted probability of lateralization in the external validation cohort.

RESULTS: The validation cohort included 342 PA patients who underwent AVS (mean age, 52.1 years [SD, 11.5]; 201 [58.8%] male; 186 [54.4%] with lateralization). Six published models were assessed. All models demonstrated low-to-moderate discrimination in the validation set (C-statistics; range, 0.60-0.72), representing a marked decrease compared to the derivation sets (range, 0.80-0.87). Comparison of observed and predicted probabilities of unilateral PA revealed significant miscalibration. Calibration-in-the-large for every model was >0 (range, 0.35-1.67), signifying systematic underprediction of lateralizing disease. Calibration slopes were consistently <1 (range, 0.35-0.87), indicating poor performance at the extremes of risk.

CONCLUSIONS: Overall, clinical prediction models did not accurately predict AVS lateralization in this large cohort. These models cannot be reliably used to inform the decision to pursue AVS for most patients.

PMID:34958097 | DOI:10.1093/ajh/hpab195

Biostatistics. 2021 Dec 27:kxab042. doi: 10.1093/biostatistics/kxab042. Online ahead of print.

ABSTRACT

Univariate spatio-temporal models for areal count data have received great attention in recent years for estimating risks. However, models for studying multivariate responses are less commonly used mainly due to the computational burden. In this article, multivariate spatio-temporal P-spline models are proposed to study different forms of violence against women. Modeling distinct crimes jointly improves the precision of estimates over univariate models and allows to compute correlations among them. The correlation between the spatial and the temporal patterns may suggest connections among the different crimes that will certainly benefit a thorough comprehension of this problem that affects millions of women around the world. The models are fitted using integrated nested Laplace approximations and are used to analyze four distinct crimes against women at district level in the Indian state of Maharashtra during the period 2001-2013.

PMID:34958093 | DOI:10.1093/biostatistics/kxab042

J Infect Dis. 2021 Dec 27:jiab626. doi: 10.1093/infdis/jiab626. Online ahead of print.

ABSTRACT

BACKGROUND: SARS-CoV-2 infection has been associated with increased risk of adverse perinatal health outcomes. However, few large-scale, community-based epidemiological studies have been conducted.

METHODS: We conducted a national cohort study using de-identified administrative claims data for 78,283 pregnancies with estimated conception before 30 April 2020 and pregnancy end after 11 March 2020. We identified maternal infections using diagnostic and laboratory testing data. We compared the risk of pregnancy outcomes using Cox proportional hazard models treating COVID-19 as a time-varying exposure and adjusting for baseline covariates.

RESULTS: 2,655 (3.4%) pregnancies had a documented SARS-CoV-2 infection; 3.4% required admission to intensive care, invasive mechanical ventilation or ECMO treatment. COVID-19 during pregnancy was not associated with risk of miscarriage, antepartum hemorrhage, or stillbirth, but was associated with 2-3 fold higher risk of induced abortion (adjusted hazard ratio [aHR] 2.60, 95% CI 1.17-5.78), c-section (aHR 1.99, 95% CI 1.71-2.31), clinician-initiated preterm birth (2.88; 95% CI 1.93, 4.30), spontaneous preterm birth (aHR 1.79, 95% CI 1.37-2.34), fetal growth restriction (aHR 2.04, 95% CI 1.72-2.43), and postpartum hemorrhage (aHR 2.03, 95% CI 1.6-2.63).

CONCLUSIONS: Prenatal SARS-CoV-2 infection was associated with increased risk of adverse pregnancy outcomes. Prevention could have fetal health benefits.

PMID:34958090 | DOI:10.1093/infdis/jiab626

Malays J Pathol. 2021 Dec;43(3):425-434.

ABSTRACT

INTRODUCTION: In line with the association of prostaglandin-endoperoxide synthase 2 (PTGS2) and defensin beta 1 (DEFB1) single nucleotide polymorphisms (SNPs) with periodontitis among the Chinese and European populations, the current study was aimed to assess the same association among the Malays in Malaysia.

METHODS: Blood samples of individuals with periodontitis (PD) (n=72) and periodontally healthy (PH) (n=62) donors were obtained from Malaysian Periodontal Database and Biobanking system (MPDBS). Genomic DNA samples were analyzed for three PTGS2 SNPs (rs5275, rs20417, rs689466,) and one DEFB1 SNP (rs1047031) using Taqman SNP genotyping assays. Notably, rs20417 and rs689466 were located in the promoter region while rs5275 and rs1047031 were located in the 3′ untranslated region of the transcript. Association between the SNPs and PD were then analyzed using genotypic association analysis (additive, dominant and recessive models).

RESULTS: The allelic frequency for the rs689466-G was higher in PD group (35.2%) compared that in PH group (29.0%). However, the association of rs689466-G and other SNPs with PD was not statistically significant (at 95% CI). No associations were observed for genotypic associations between the PTGS2 and DEFB1 SNPs with PD susceptibility.

CONCLUSIONS: PTGS2 (rs5275, rs20417, and rs689466) and DEFB1 (rs1047031) polymorphism was not associated with PD in Malays, unlike the Chinese, Taiwanese & European population. This suggests that other causal variants might be involved in the development and progression of PD among Malays.

PMID:34958064

Malays J Pathol. 2021 Dec;43(3):397-404.

ABSTRACT

INTRODUCTION: Breslow density is a newly defined biomarker, independent of Breslow thickness. We aimed to investigate the relationship of Breslow density with other clinicopathological prognostic factors and its effect on the overall survival and disease-free survival in patients with cutaneous melanomas.

MATERIALS & METHODS: This was a single-centre retrospective study of patients (n = 19) diagnosed with cutaneous malignant melanomas in our hospital between 2011 and 2019 were included in the study. The exclusion criteria were in situ melanomas, punch or incisional biopsies and metastasis at the time of the diagnosis. Breslow density was determined by reevaluating slides obtained at the time of the initial diagnoses. The effect of Breslow density on survival was determined using univariate and multivariate Cox proportional risk analyses.

RESULTS: In terms of the overall survival, mortality risk increased as Breslow density increased (p = 0.044). Breslow density was not significantly associated with the overall survival in the multivariate model (p = 0.078). In terms of disease-free survival, the risk of metastasis or recurrence increased 1.229- fold in accordance with an increase in Breslow thickness (CI: 1.057-1.428), whereas increased Breslow density increased the metastasis or recurrence risk 1.059-fold (CI: 1.008-1.112). In the multivariate model, only Breslow density was statistically significant (p = 0.046).

CONCLUSIONS: As a semi-quantitative and subjective measurement, Breslow density is not a completely accurate representation of the invasive tumour load. However, the measurement is practical and low cost and requires no additional equipment. Therefore, Breslow density can be measured in every laboratory. Considering the value of Breslow density in predicting the prognosis in patients with cutaneous melanomas and strong inter-observer compliance observed in the present study, we believe that it would be useful to include this measurement in pathology reports.

PMID:34958061

Malays J Pathol. 2021 Dec;43(3):375-380.

ABSTRACT

INTRODUCTION: To evaluate the association of Procalcitonin (PCT) with severity in Coronavirus disease 2019 (COVID-19), hospitalised patients and to test the hypothesis that it is an independent predictor of mortality.

MATERIALS AND METHODS: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University (AKU), Karachi Pakistan. Electronic medical records of all in-patients including both genders and all age groups with documented COVID-19 from March to August 2020 were reviewed and recorded on a pre-structured performa. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. Between-group differences were tested using the Chi-square and Mann-Whitney’s U-test. The receiver operating characteristic curve was plotted for serum PCT with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analysed using SPSS.

RESULTS: 336 patients were reviewed as declared COVID-19 positive during the study duration, and 136 were included in the final analysis including 101 males and 35 females. A statistically significant difference in PCT was found between severe and non-severe COVID-19 (p value=0.01); and survivors and nonsurvivors (p value<0.0001). PCT, older age and increased duration of hospital stay were revealed as variables independently associated with mortality. On ROC analysis, an AUC of 0.76 for mortality prediction was generated for PCT.

CONCLUSION: Baseline serum PCT concentration is a promising predictor of mortality and severity in COVID-19 cases when considered in combination with clinical details and other laboratory tests.

PMID:34958058

J Parkinsons Dis. 2021 Dec 22. doi: 10.3233/JPD-212819. Online ahead of print.

ABSTRACT

BACKGROUND: Recent randomized clinical trials using hydrophobic statins reported no influence on Parkinson’s disease (PD) clinical progression. Hydrophobicity is a key determinant for blood-brain barrier penetrance.

OBJECTIVE: Investigate a potential effect of statins on PD progression.

METHODS: Statin use was determined at baseline and subtyped according to hydrophobicity in 125 PD patients participated PD Biomarker Program (PDBP, 2012-2015) at our site. Clinical (N = 125) and susceptibility MRI (N = 86) data were obtained at baseline and 18-months. Movement Disorders Society-Unified PD Rating Scales were used to track progression of non-motor (MDS-UPDRS-I) and motor (MDS-UPDRS-II) symptoms, and rater-based scores (MDS-UPDRS-III) of patients in the “on” drug state. R2 * values were used to capture pathological progression in the substantia nigra. Associations between statin use, its subtypes, and PD progression were evaluated with linear mixed effect regressions.

RESULTS: Compared to statin non-users, overall statin or lipophilic statin use did not significantly influence PD clinical or imaging progression. Hydrophilic statin users, however, demonstrated faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 4.8, p = 0.010)] and nigral R2 * (β= 3.7, p = 0.043). A similar trend was found for MDS-UPDRS-II (β= 3.9, p = 0.10), but an opposite trend was observed for rater-based MDS-UPDRS-III (β= -7.3, p = 0.10). Compared to lipophilic statin users, hydrophilic statin users also showed significantly faster clinical progression of non-motor symptoms [MDS-UPDRS-I (β= 5.0, p = 0.020)], but R2 * did not reach statistical significance (β= 2.5, p = 0.24).

CONCLUSION: This study suggests that hydrophilic, but not lipophilic, statins may be associated with faster PD progression. Future studies may have clinical and scientific implications.

PMID:34958045 | DOI:10.3233/JPD-212819

J Alzheimers Dis. 2021 Dec 22. doi: 10.3233/JAD-215163. Online ahead of print.

ABSTRACT

BACKGROUND: Tauopathy is a primary neuropathological hallmark of Alzheimer’s disease with a strong relationship to cognitive impairment. In the brain, tau aggregation is associated with the regulation of tau kinases and the binding ability of tau to microtubules.

OBJECTIVE: To explore the potential for using specific polygenic risk scores (PRSs), combining the genetic influences involved in tau-protein kinases and the tau-protein binding pathway, as predictors of tau pathology and cognitive decline in non-demented individuals.

METHODS: We computed a pathway-specific PRS using summary statistics from previous large-scale genome-wide association studies of dementia. We examined whether PRS is related to tau uptake in positron emission tomography (PET), tau levels, and the rate of tau level changes in cerebrospinal fluid (CSF). We further assessed whether PRS is associated with memory impairment mediated by CSF tau levels.

RESULTS: A higher PRS was related to elevated CSF tau levels and tau-PET uptake at baseline, as well as greater rates of change in CSF tau levels. Moreover, PRS was associated with memory impairment, mediated by increased CSF tau levels. The association between PRS and tau pathology was significant when APOE was excluded, even among females. However, the effect of PRS on cognitive decline appeared to be driven by the inclusion of APOE.

CONCLUSION: The influence of genetic risk in a specific tau-related biological pathway may make an individual more susceptible to tau pathology, resulting in cognitive dysfunction in an early preclinical phase of the disease.

PMID:34958026 | DOI:10.3233/JAD-215163