Effect of chronic kidney disease on adverse drug reactions to anti-tubercular treatment: a retrospective cohort study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function. METHODOLOGY: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio. RESULTS: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p ≤ 0.0001). The matched cohort showed similar results. CONCLUSION: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

Uremic pruritus: prevalence, determinants, and its impact on health-related quality of life and sleep in Indian patients undergoing hemodialysis.

BACKGROUND: Uremic pruritus has an impact on the quality of life and sleep of hemodialysis patients, but the majority of cases go unreported and untreated unless severe, due to a lack of awareness. The purpose of this study is to determine the prevalence, associated factors, and impact on health-related quality of life (HR-QOL) and sleep in hemodialysis patients. METHODOLOGY: A single-center observational study of 3 months wherein 120 adults on maintenance hemodialysis were included. Baseline characteristics, dialysis-related factors, and lab parameters influencing uremic pruritus were recorded. Those with uremic pruritus completed "12-item pruritus severity scale (12-PSS)", "SKINDEX10", and "Itch-MOS" questionnaires to evaluate severity, impact on HR-QOL, and sleep respectively. RESULTS: Sixty seven over one hundred twenty (55.83%) patients had pruritus and majority were mild (40.83%) as per 12-PSS. Those with pruritus (n=67) had a mean age of 56.5±11.3 years, most were males (82%), chronic glomerulonephritis (29.1%) was the commonest cause of end-stage kidney disease, 3 active smokers, and 4 seropositive. 65(97%) patients were on twice-weekly dialysis, 36/67 had <5 years' dialysis vintage and acceptable adequacy. There was no significant association between uremic pruritus and dialysis-related/laboratory parameters. Patients with uremic pruritus demonstrated significantly worse "HR-QOL" (p<0.001) on the "SKINDEX-10", and patients' "Itch-MOS" scores demonstrated a significant decline in sleep quality with increasing pruritus severity (p<0.001). CONCLUSION: The majority of patients on maintenance hemodialysis experience uremic pruritus. None of the clinical characteristics, dialysis-related factors, and laboratory parameters affected uremic pruritus. Uremic pruritus patients had the worst HR-QOL & their sleep quality significantly declined as pruritus severity escalated. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: Study approval was obtained from Institutional Research Committee and Institutional Ethical Committee (IEC 642/2021). Clinical Trial Registry of India (CTRI) registration (CTRI/2022/01/039143) was also obtained.

COVID-19 and tuberculosis coinfection: A case-control study from a tertiary care center in South India.

Context: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB), are presently the major infectious diseases imposing a consequential public health threat and their coinfection has a significant impact on the outcome. Aims: To evaluate the clinical features and outcomes of COVID-19-TB coinfected cases compared to solely COVID-19-infected cases. Settings and Design: A retrospective observational study was conducted between August 1, 2020, to February 28, 2022, at a tertiary care hospital. Materials and Methods: In this case-control study, an equal number of gender-age-matched COVID-19 and TB coinfected patients and COVID-19 cases without TB were included using simple random sampling. Statistical Analysis Used: The data was analyzed using SPSS v 26. Categorical variables were compared using the Chi-square test, and an independent t-test or Mann-Whitney U test was applied for the quantitative variables in the univariate analysis. A P-value of less than 0.05 was considered significant. Results: A total of 27 patients were included in each group. Upper lobe involvement (44%) and pleural effusion (22%) were significantly more common in TB-COVID-19 cases when compared to the control group (7% and 4%, respectively; P < 0.05). Moreover, median levels of C-reactive protein and ferritin were significantly higher in TB-COVID-19 coinfection. Conclusions: Chest radiology and a higher level of certain biomarkers like C-reactive protein and ferritin can help to suspect TB in COVID-19 patients and vice-versa.

Unveiling antioxidant and anti-cancer potentials of characterized Annona reticulata leaf extract in 1,2-dimethylhydrazine-induced colorectal cancer in Wistar rats.

BACKGROUND: Colorectal cancer (CC) is the third most common cancer in the world. Annona reticulata (AR) also known as bullock's heart, is a traditional herb. AR leaf extract was initially investigated for its anti-bacterial, anti-inflammatory, anti-malarial, anti-helminthic, anti-stress, and wound healing properties. Only a few in vitro cancer studies have been conducted on AR. Although few studies have linked AR leaf extract to many cancers, comprehensive studies addressing regulation, biological functions, and molecular mechanisms leading to CC pathogenesis are clearly lacking. OBJECTIVES: The present study aimed to explore the antioxidant and anti-cancer potentials of AR leaf extract in CC. MATERIALS AND METHODS: The MTT assay was used to test the anti-proliferative activity of AR leaf extract in vitro on the HCT116 cell line. Qualitative and quantitative phytochemical characterization was carried out using gas chromatography: mass spectrometry (GC-MS). 1,2-dimethylhydrazine (DMH) was used to establish CC model in female Wistar rats. The acute toxicity of AR leaf extract was tested in accordance with OECD guidelines. Aberrant Crypt Foci (ACF) count, organ index, and hematological estimations were used to screen for in vivo anti-cancer potential. The antioxidant activity of colon homogenate was determined. RESULTS: The alcoholic leaf extract (IC50, 0.55 µg/ml) was found to be more potent than the aqueous extract. Using GC-MS, a total of 108 compounds were quantified in the alcoholic leaf extract. The LD 50 value was found to be safe at a dose of 98.11 mg/kg of body weight. AR alcoholic leaf extract significantly (p < 0.05) decreased ACF count and normalized colon length/weight ratio. AR leaf extract increased RBC, hemoglobin and platelets levels. The AR alcoholic leaf extract reduced the DMH-induced tumors and significantly (p < 0.05) increased the activity of endogenous antioxidant enzymes such as catalase, reduced glutathione, superoxide dismutase, and decreased the lipid peroxidase activity. AR leaf extract reduced the inflammation caused by DMH and helped to repair the colon's damaged muscle layers. CONCLUSION: Based on the findings from the present study, it can be concluded that the alcoholic leaf extract of AR has antioxidant and anti-proliferative properties and can aid in the prevention of CC development and dysplasia caused by DMH.

Efficacy and safety of corticosteroids in acute respiratory distress syndrome: An overview of meta-analyses.

BACKGROUND: Evidence-based recommendations on the efficacy and safety of corticosteroids in acute respiratory distress syndrome (ARDS) remain a therapeutic challenge. Findings from several systematic reviews and meta-analyses are inconsistent. We aimed to assess the published meta-analyses through a systematic review approach and provide further insight into the current uncertainty and also to perform an updated meta-analysis from all the available primary studies. METHODOLOGY: We followed the Preferred Reporting Items for Systematic Review (PRISMA) guidelines to establish the patients, intervention, control and outcome (PICO) for reviewing published meta-analyses. Data sources such as PubMed/MEDLINE, SCOPUS, Cochrane and Google Scholar from inception to February 2021 were accessed. Prevention of ARDS, mortality, ventilator-free days, ICU stay and safety in terms of occurrence of adverse effects were the patient-related outcomes. The review also assessed meta-analysis design-related outcomes which includes the quality of meta-analysis, factors contributing to the risk of bias, extent and sources of heterogeneity, publication bias and robustness of findings. AMSTAR-2 checklist assessed the quality of published meta-analyses. RESULTS: A total of 18 meta-analyses were reviewed comprising a total of 38 primary studies and 3760 patients. Fourteen studies were in ARDS, three in community-acquired pneumonia and one in critical care. The overall quality of meta-analyses was observed to be critically low to high. A non-significant risk of publication bias and non-significant level of heterogeneity was observed in the reviewed meta-analysis. Corticosteroid was significantly effective in preventing ARDS among CAP patients. The effect of corticosteroids on mortality was observed to be still inconsistent, whereas significant improvement was observed with ICU and ventilator outcomes compared with the control group. Our meta-analysis observed a significant reduction of mortality in RCTs (RR: 0.78; 95% CI: 0.61 to 0.99) and the duration of mechanical ventilation (MD: -4.75; 95% CI: -7.63 to -1.88); and a significant increase in ventilator-free days (MD: 6.03; 95% CI: 3.59 to 8.47) and ICU-free days (MD: 8.04; 95% CI: 2.70 to 13.38) in ARDS patients treated with corticosteroids compared with the control group. CONCLUSION: The quality of included studies ranged from critically low to high demonstrating inconsistency in risk of bias. While older studies found no significant effect, recent meta-analyses of RCTs found a significant mortality reduction in the corticosteroid group with considerable levels of heterogeneity. The updated meta-analysis by our team found a significant reduction in mortality in the pooled estimation of RCTs but not in cohort studies. Corticosteroid therapy was effective in terms of ICU and ventilator outcomes with minimal safety concerns. Future meta-analyses should be well executed with specific research questions and well performed with minimal risk of bias to produce good quality evidence.