Long term impact on offspring (5-11 years of age) of metformin use in pregnancy in mothers with diabetes: A systematic review and meta-analysis.

BACKGROUND: Data is scant on impact of metformin use in gestational diabetes (GDM)/ diabetes in pregnancy (DIP) on long-term outcomes in children and mothers beyond 5-years of child-birth. This systematic-review and meta-analysis aimed to evaluate the long-term impact of metformin use in pregnancy on children and their mothers. METHODS: Electronic databases were searched for studies evaluating metformin as compared to insulin for managing GDM/DIP. Primary outcome was to evaluate changes in body-mass index (BMI) in children at 5-11 years age. Secondary outcomes were to assess alterations in other anthropometric measures, obesity, changes in lipids and adipo-cytokines in children and mothers. RESULTS: Children at 9-years age, born to mothers who were treated with metformin during pregnancy had similar BMI [MD1.09kg/m2(95%CI:-0.44-2.62);P=0.16;I2=16%], waist-circumference to height-ratio [MD0.13(95%CI:-0.05-0.30);P=0.16;I2=94%], dual-energy X-ray absorptiometry (DXA) total fat-mass [MD0.68kg(95%CI:-2.39-3.79);P=0.66;I2=70%], DXA-total fat-percent [MD 0.04%(95%CI:-3.44-3.51);P=0.98;I2=56%], DXA-total fat-free mass [MD 0.81kg (95%CI:-0.96-2.58);P=0.37;I2=55%], MRI visceral adipose tissue [MD 80.97cm3(95%CI:-136.47-298.41); P=0.47;I2=78%] and magnetic-resonance spectroscopy liver-fat percentage [MD 0.27%(95% CI:-1.26-1.79);P=0.73;I2=0%], compared to those born to mothers who were treated with insulin. Serum adiponectin, leptin, alanine-aminotransferase and ferritin were comparable among groups. In children between 9-11 years age, occurrence of obesity, diabetes or challenges in motor and social development were comparable between the 2 groups. After 9 years of childbirth, BMI and risk of developing diabetes were similar in the two groups of women. CONCLUSION: Metformin use in pregnancy did not show any adverse effects when compared to insulin on long-term outcomes in children and their mothers.

Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

Cycle threshold values of SARS-CoV-2 RNA in conjunctival swabs and nasopharyngeal secretions: a comparative study from a tertiary care center in India.

PURPOSE: To detect the viral RNA load of SARS-CoV-2 in conjunctival swabs of COVID-19 patients, and compare with nasopharyngeal swabs. METHODS: Conjunctival swabs of COVID-19 patients (with PCR positive nasopharyngeal swabs) were subjected to quantitative reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 RNA. The cycle threshold (Ct) values of Open Reading Frame 1 (ORF 1 Ab gene) and nucleoprotein (N gene) PCRs were used to assess the viral RNA load, and compare them with the baseline values of nasopharyngeal swabs. RESULTS: Of 93 patients, 17 (18.27%) demonstrated SARS-CoV-2 RNA in conjunctival swabs. Baseline nasopharyngeal swabs were collected at a median of 2 days; while, the conjunctival swabs were collected at median 7 days, from onset of illness (p < 0.001). Despite a significant delay in conjunctival swab collection than nasopharyngeal swabs, the Ct values (ORF or N gene PCRs) were comparable between nasopharyngeal swab and conjunctival swab samples. Subsequently, during the recovery period, in four of these 17 patients (with conjunctival swab positivity), when the second nasopharyngeal swab was 'negative', the conjunctival swab was 'positive'. CONCLUSION: The conjunctival swabs demonstrated SARS-CoV-2 RNA in 17 (18.27%) of 93 COVID-19 patients. Our results may suggest a delayed or a prolonged shedding of the virus/viral RNA on the ocular surface than in nasopharyngeal mucosa.

Rapid Decline of SARS-CoV-2 Viral Load in Single vs. Double-Dose (Short-Interval <6 Weeks) ChAdOx nCoV-19 Vaccinated Health-Care Workers.

The present work was carried out during the emergence of Delta Variant of Concern (VoC) and aimed to study the change in SARS CoV-2 viral load in Covishield vaccinated asymptomatic/mildly symptomatic health-care workers (HCWs) to find out the optimum isolation period. The SARS CoV-2 viral load was carried out in sequential samples of 55 eligible HCWs which included unvaccinated (UnV; n = 11), single-dose vaccinated (SDV, n = 20) and double-dose vaccinated [DDV, n = 24; short-interval (<6 weeks)] subjects. The mean load of envelope (E) gene on day 5 in SDV [0.42 × 105 copies/reaction] was significantly lower as compared to DDV [6.3 × 105 copies/reaction, P = 0.005] and UnV [6.6 × 105 copies/reaction, P = 0.001] groups. The rate of decline of SARS CoV-2 viral load in the initial 5 days of PCR positivity was significantly higher in SDV as compared to that in DDV (Mean log decline 0.39 vs. 0.19; P < 0.001). This was possibly due to interference of adenoviral immunity of first dose of adenovirus-vectored vaccine in double-dose vaccinated HCWs who had received vaccines within a shorter interval (<6 weeks).

Neisseria mucosa: A not so Benign Culprit of urinary tract infection: A case report.

Neisseria mucosa is saprophytic human commensal but reported as a causative agent in a couple of urinary tract infections [UTI] in susceptible individuals. In the present case, a young girl with long standing neurological problems presented with bladder outlet obstruction and fever. Her urine culture yielded Neisseria mucosa which was susceptible to broad spectrum penicillins, aminoglycosides, cephalosporins, ciprofloxacin, and azithromycin. She recovered with suitable dosage of amoxicillin clavulanic acid and was discharged. Isolation of N. mucosa here becomes clinically significant as this girl had various ureteric and lower limb weaknesses in past and was symptomatic for UTI with this infection.

The continuum of liver injury with severity of dengue fever: A retrospective observational study.

BACKGROUND: Dengue is a major international health concern prevalent in tropical and sub-tropical countries. There are a paucity of studies on the relationship of hepatic complications with inflammatory parameters in dengue infection. METHODS: Single-centre observational study was conducted at the tertiary care centre in North India. Patients (>12 years) diagnosed with dengue infection between August and November 2021 were enrolled in the study. The frequency of hepatic derangements and their associations with inflammatory severity was analysed. RESULTS: Based on the clinical symptoms, 170 patients were classified into three categories, namely, dengue fever, warning dengue and severe dengue. Higher incidence of liver dysfunction was observed in severe dengue patients with median values of aspartate aminotransferase (AST) (3051 U/L, p < 0.001), alanine aminotransferase (ALT) (1792 U/L, p = 0.009), alkaline phosphatase (172 U/L, p = 0.001), T.Bil (34.2 µmol/L, p < 0.001), albumin (30 g/L, <0.001), and gamma-glutamyl transferase (152 U/L, p < 0.001) along with inflammatory marker C-reactive protein (CRP) (43 mg/dL, p < 0.001) highly deranged, in comparison to patients with/without warning signs. Median levels of CRP were found to be positively and significantly correlated with the median levels of AST and ALT (p < 0.05, r = 0.99) in all three categories of dengue patients. Liver injury was noted in 107 (63%) of the cohort, and mixed type of liver injury involving both hepatocellular and cholestatic patterns was observed as the most common type of injury (n = 50, 29.4%). Liver injury correlated with the severity of dengue illness as about 85% of severe dengue patients had significant liver injury (p = 0.014). CONCLUSION: In dengue patients, the association of the liver injury with inflammatory severity suggests that the mechanism of liver injury may be related to inflammatory response apart from the hepatotropic nature of the virus.

Role of Novel Glucagon-like Peptide-1 Receptor Analogue Polyethylene Glycol Loxenatide in Type 2 Diabetes: A Systematic Review and Meta-analysis.

Background: Polyethylene glycol loxenatide (peg-loxenatide) is a novel glucagon-like peptide-1 receptor agonist developed and available for clinical use in China. This meta-analysis was performed as no meta-analysis has analysed the efficacy and safety of peg-loxenatide in type 2 diabetes (T2DM). Methods: Electronic databases were systematically reviewed for RCTs having patients living with T2DM receiving peg-loxenatide in treatment arm and placebo/any other diabetes medicine in control arm. The primary outcome was to evaluate changes in glycated haemoglobin. The secondary outcomes were to evaluate alterations in weight, blood pressure, fasting glucose, prandial glucose, lipids, and adverse events. Results: Data from four trials (718 patients) were analysed. Over 12-24 weeks of clinical use, HbA1c was significantly lower in patients receiving standard-dose peg-loxenatide (100 mcg/week) {MD -0.95% [95% confidence interval (CI): -1.19 to -0.71]; P < 0.01; I2 = 76%} and high-dose peg-loxenatide (200 mcg/week) [MD -1.15% (95% CI: -1.47 to -0.82); P < 0.01; I2 = 90%], as compared to placebo. Standard-dose peg-loxenatide was not associated with increased occurrence of nausea [RR 2.87 (95% CI: 0.56 to 14.72); P = 0.21; I2 = 10%], vomiting [RR 4.73 (95% CI: 0.53 to 41.88); P = 0.16; I2 = 0%], and anorexia [RR 0.78 (95% CI: 0.18 to 3.28); P = 0.73; I2 = 0%]. Occurrence of nausea [RR 16.85 (95% CI: 3.89 to 72.92); P < 0.01; I2 = 10%], vomiting [RR 15.90 (95% CI: 2.99 to 84.55); P < 0.01; I2 = 0%], and anorexia [RR 3.85 (95% CI: 1.24 to 11.88); P = 0.02; I2 = 0%] was significantly higher with high-dose peg-loxenatide, as compared to placebo. Conclusion: Peg-loxenatide (100 mcg/week) is the most appropriate dose for clinical use as it is associated with good glycaemic efficacy with minimal gastro-intestinal side effects.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Optimal use of once weekly icodec insulin in type-2 diabetes: An updated meta-analysis of phase-2 and phase-3 randomized controlled trials.

BACKGROUND: Previously published meta-analysis have analysed data from 3 small phase-2 randomized controlled trials (RCTs). Since then, 5 big phase-3 RCTs have been published on use of icodec in type-2 diabetes (T2D). This updated systematic review aimed to establish the best practices and safety of icodec in T2D. METHODS: Databases were searched for RCTs involving T2D patients receiving icodec. Primary outcome was change in HbA1c. Secondary outcomes were alterations in glycaemic parameters and adverse events. RESULTS: Data from 8 studies (4317 patients) was analysed. Compared to other basal insulins, icodec had comparable HbA1c lowering at 16-weeks [MD-0.19 %(95%CI: 0.58-0.20); P = 0.35; I2 = 92 %], better HbA1c lowering at 26-weeks [MD-0.19 %(95%CI: 0.35-0.013); P = 0.02; I2 = 94 %] and 52-weeks [MD -0.28 %(95%CI: 0.45-0.12); P = 0.0008; I2 = 100 %]. Percentage of participants achieving HbA1c<7 % with icodec was higher at 16-weeks [OR2.37(95%CI:1.05-5.35); P = 0.04], comparable at 26-weeks [OR1.38(95%CI:0.91-2.11); P = 0.13; I2 = 80 %], and higher at 52-weeks [OR1.55(95%CI:1.30-1.85); P < 0.00001; I2 = 0 %]. Percentage of participants achieving HbA1c<7 % without level 2/3 hypoglycaemia was higher with icodec at 26-weeks [OR1.37(95%CI:1.10-1.71); P = 0.004; I2 = 28 %] and 52-weeks [OR1.48(95%CI:1.24-1.77); P < 0.001; I2 = 0 %]. At 26-weeks, injection-site reactions was higher with icodec [OR1.95(95%CI:1.06-3.56); P = 0.03; I2 = 0 %]. At 26-weeks level-1 hypoglycemia [OR1.40(95%CI:1.02-1.94); P = 0.04; I2 = 58 %], but not level-2/3 hypoglycaemia was higher with icodec. Subset analysis revealed increased occurrence of level-1 [OR 4.19 (95 % CI: 3.20-5.50); P < 0.00001] and level-2 [OR 3.97 (95 % CI: 3.04-5.18); P < 0.00001] hypoglycaemia in participants who received one-time additional 50 % icodec loading dose as compared to those who did not. At 26-weeks, weight-gain was significantly higher with icodec [MD0.61 kg(95%CI:0.38-0.84); P < 0.00001; I2 = 98 %]. CONCLUSION: Icodec insulin is well tolerated with glycaemic efficacy similar to all other available basal insulins.

Depression, Anxiety, and Quality of Life in Patients Treated with Single Infusion Tocilizumab for COVID-19: A Follow-up, Controlled Study.

Background: The inflammatory state that characterizes COVID-19 may contribute to depression, anxiety, other morbidities, and mortality. Interleukin-6 blocker tocilizumab has been used as a treatment modality in COVID-19 as an anti-inflammatory agent. Tocilizumab has also been studied for its potential use in preventing depression in other patient groups, with mixed results. This study was designed to study subsequent depression, anxiety, and quality of life (QOL) in patients treated with tocilizumab plus standard care versus standard care alone, for moderate to severe COVID-19 pneumonia. Methods: Patients admitted with moderate to severe COVID pneumonia, treated with tocilizumab plus standard treatment, and discharged from the hospital were identified. Age- and gender-matched controls who had received standard treatment alone for COVID-19 pneumonia during the same time frame were identified. After obtaining consent, these patients were followed up and assessed at 3 and 6 months on measures of depression (PHQ-9), anxiety (GAD-7), and QOL (EQ-5D-5L). Results: 39 patients in the tocilizumab group and 41 in the control group were followed up at 3 and 6 months. Patients in both groups were comparable in sociodemographic and clinical parameters. The prevalence of clinically significant depression in the tocilizumab group at 3 and 6 months was 33.33% and 5.12%, respectively, whereas in control group it was 31.7% and 4.87%, respectively. Analysis of EQ-5D health profiles revealed that the maximum problems were reported in the dimension of mobility: 43.7% at 3 months and 35% at 6 months. Conclusions: Depressive and anxiety symptoms and impairment in QOL were reported more frequently and with greater severity in patients in the tocilizumab group at three months but not at six months. Psychological morbidity and impairment in QOL were modest and improved from 3 to 6 months.

Frequency, outcomes, and need for intervention in stricturing gastrointestinal tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity. AIM: To conduct a systematic review of the prevalence of stricturing disease in abdominal and gastrointestinal tuberculosis and response to antitubercular therapy (ATT). METHODS: We searched Pubmed and Embase on 13th January 2022, for papers reporting on the frequency and outcomes of stricturing gastrointestinal tuberculosis. The data were extracted, and pooled prevalence of stricturing disease was estimated in abdominal tuberculosis and gastrointestinal (intestinal) tuberculosis. The pooled clinical response and stricture resolution (endoscopic or radiologic) rates were also estimated. Publication bias was assessed using the Funnel plot and Egger test. The risk of bias assessment was done using a modified Newcastle Ottawa Scale. RESULTS: Thirty-three studies reporting about 1969 patients were included. The pooled prevalence of intestinal strictures in abdominal tuberculosis and gastrointestinal TB was 0.12 (95%CI 0.07-0.20, I2 = 89%) and 0.27 (95% CI 0.21-0.33, I2 = 85%), respectively. The pooled clinical response of stricturing gastrointestinal tuberculosis to antitubercular therapy was 0.77 (95%CI 0.65-0.86, I2 = 74%). The pooled stricture response rate (endoscopic or radiological) was 0.66 (95%CI 0.40-0.85, I2 = 91%). The pooled rate of need for surgical intervention was 0.21 (95%CI 0.13-0.32, I2 = 70%), while endoscopic dilatation was 0.14 (95%CI 0.09-0.21, I2 = 0%). CONCLUSION: Stricturing gastrointestinal tuberculosis occurs in around a quarter of patients with gastrointestinal tuberculosis, and around two-thirds of patients have a clinical response with antitubercular therapy. A subset of patients may need endoscopic or surgical intervention. The estimates for the pooled prevalence of stricturing disease and response to ATT had significant heterogeneity.

The 'myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19' is far from reality.

The efficacy of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19 was contentious. In this randomized control double-blind clinical trial, asymptomatic individuals with direct contact with laboratory-confirmed COVID-19 cases were randomized into PEP/HCQ (N = 574) and control/placebo (N = 594) group. The PEP/HCQ group received tablet HCQ 400 mg q 12 hourly on day one followed by 400 mg once weekly for 3 weeks, and the control/Placebo group received matching Placebo. The incidence of COVID-19 was similar (p = 0.761) in PEP [N = 24 out of 574, (4.2%)] and control [N = 27 out of 594, (4.5%)] groups. Total absolute risk reduction for the incidence of new-onset COVID-19 was -0.3% points with an overall relative risk of 0.91 (95% confidence interval, 0.52 to 1.60) and the number needed to treat (NNT) was 333 to prevent the incident of one case of COVID-19. The study found that, PEP with HCQ was not advantageous for the prevention of COVID-19 in asymptomatic individuals with high risk for SARS-CoV-2 infection. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance.

Recombinant protein subunit COVID-19 vaccine-induced Guillain-Barré Syndrome in an adolescent: A case report.

Guillain-Barré Syndrome (GBS), an autoimmune neurological disease of peripheral nerves, has been causally associated with COVID-19 vaccination in adults. However, no such report has been published so far in children. We describe a 13-year-old female child who presented to the emergency department with complaints of bilateral upper limb, lower limb and truncal weakness over 3 days following first dose of recombinant protein subunit COVID-19 vaccine (Corbevax). Clinical examination and nerve conduction studies showed pure motor axonal polyneuropathy with absent compound muscle action potential (CMAP) in all sampled nerves of upper and lower limbs which was consistent with the diagnosis of GBS after ruling out possible alternative aetiologies. A temporal association between first dose of protein subunit COVID-19 vaccine administered a day prior and symptom onset was noted. The causality assessment using the World Health Organization (WHO) tool for adverse event following immunization (AEFI) assessment indicated vaccine product-related reaction categorized as A1. The patient's clinical condition improved after seven sessions of plasmapheresis. The purpose of this report is to create awareness among health care professionals about COVID-19 vaccine-induced GBS in children as early diagnosis and management can be critical in avoiding complications and improving patient outcomes.

Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis.

BACKGROUND: No meta-analysis has analysed efficacy and safety of fast-acting aspart insulin (FIAsp) with insulin pump in type 1 diabetes mellitus (T1DM). METHODS: Electronic databases were searched for randomised controlled trials (RCTs) involving T1DM patients on insulin pump receiving FIAsp in intervention arm, and placebo/active comparator insulin in control arm. Primary outcome was to evaluate changes in 1- and 2-hour post-prandial glucose (1hPPG and 2hPPG). Secondary outcomes were to evaluate alterations in percentage time with blood glucose <3.9 mmol/L (hypoglycaemia), time in range (TIR) blood glucose 3.9 to 10 mmol/L, insulin requirements and adverse events. RESULTS: Data from four RCTs involving 640 patients was analysed. FIAsp use in insulin pump was associated with significantly greater lowering of 1hPPG (mean difference [MD], -1.35 mmol/L; 95% confidence interval [CI], -1.72 to -0.98; P<0.01; I2=63%) and 2hPPG (MD, -1.19 mmol/L; 95% CI, -1.38 to -1.00; P<0.01; I2=0%) as compared to controls. TIR was comparable among groups (MD, 1.06%; 95% CI, -3.84 to 5.96; P=0.67; I2=70%). Duration of blood glucose <3.9 mmol/L was lower in FIAsp group, approaching significance (MD, -0.91%; 95% CI, -1.84 to 0.03; P=0.06; I2=0%). Total hypoglycaemic episodes (risk ratio [RR], 1.35; 95% CI, 0.55 to 3.31; P=0.51; I2=0%), severe hypoglycaemia (RR, 2.26; 95% CI, 0.77 to 6.66; P=0.14), infusion site reactions (RR, 1.35; 95% CI, 0.63 to 2.93; P=0.77; I2=0%), and treatment-emergent adverse events (RR, 1.13; 95% CI, 0.80 to 1.60; P=0.50; I2=0%) were comparable. CONCLUSION: FIAsp use in insulin pump is associated with better post-prandial glycaemic control with no increased hypoglycaemia or glycaemic variability.

Adult-onset Still's disease and fever of unknown origin in India.

Despite an essential differential diagnosis for fever of unknown origin (FUO) in young adults, adult-onset Still's disease (AOSD) is infrequently considered and remained underdiagnosed in low-middle-income countries. The present study analyzed the clinical, serological, radiological, and pathological characteristics of AOSD presented as FUO in India. A hospital-based retrospective study of patients aged > 13 years admitted with FUO and later diagnosed with AOSD in Postgraduate Institute of Medical Education and Research, Chandigarh (India), was conducted between January 2014 and December 2020. Petersdorf and Beeson's criteria were used to define FUO. The diagnosis of AOSD was made based on Yamaguchi's criteria. Twenty-seven patients (median age 26 years, 14 females) were enrolled. All presented with intermittent fever with a median duration of 10 weeks. The typical features of AOSD at admission were arthralgia (n = 24), hepatosplenomegaly (n = 21), spiking fever ≥ 39 °C (n = 19), lymphadenopathy (n = 18), typical rash (n = 17), and sore throat (n = 11). Leukocytosis (n = 25) and neutrophilia (n = 19) were frequent. Hyperferritinemia was universal (range, 700-145,003 ng/ml; ≥ 2000, n = 23). At admission, AOSD was suspected in only nine FUO cases, while tuberculosis (n = 16), undifferentiated connective tissue disorder (n = 14), and lymphoproliferative disorder (n = 11) were common diagnostic possibilities. Crispin et al. clinical scale detected AOSD in only 15 (55.5%) FUO patients. Whole-body imaging (n = 27), including fluorodeoxyglucose positron emission tomography (n = 12), demonstrated reticuloendothelial organ-system involvement and serositis. Seventeen (63%) patients had macrophage activation syndrome at the time of AOSD diagnosis. AOSD FUO presents with typical but nonspecific features; thus, early differentiation from common causes (e.g., tuberculosis, lymphoma) is difficult. Macrophage activation syndrome is common in AOSD with FUO presentation.

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed the safety and efficacy of lobeglitazone in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving type-2 diabetes patients receiving lobeglitazone in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glucose, lipids and adverse events. RESULTS: From initially screened 65 articles, data from 4 RCTs (828 patients) which fulfilled all criteria was analysed. Over 24 weeks, when compared to sitagliptin 100 mg/d and half maximal pioglitazone dose (15 mg/d), lobeglitazone 0.5 mg/day had comparable impact on HbA1c [MD 0.03% (95%CI: 0.11-0.17); P = 0.65; I2 = 0%], fasting glucose [MD 1.47 mg/dl (95%CI: 4.66-7.60); P = 0.64; I2 = 0%], triglycerides [MD-9.96 mg/dl (95%CI: 43.55-23.62); P = 0.56; I2 = 81%], LDL-cholesterol [MD0.74 mg/dl (95%CI: 4.60-6.09); P = 0.79; I2 = 0%] and HDL-cholesterol [MD1.55 mg/dl (95%CI: 3.72-6.82); P = 0.56]. Occurrence of treatment-emergent adverse events (AEs) [RR 1.07 (95% CI:0.78-1.47); P = 0.67; I2 = 0%] and severe AEs [RR 1.05(95%CI: 0.42-2.65); P = 0.91; I2 = 0%] were similar. Edema and weight gain were significantly higher with lobeglitazone compared to controls [RR 2.58 (95%CI: 1.08-6.17); P = 0.03; I2 = 0%]. Lobeglitazone 0.5 mg/d compared to half-maximal pioglitazone (15 mg/d), had similar edema and weight gain [RR 1.65 95% CI: 0.78-1.47)]. BMD percent changes at neck of femur was comparable in both groups [MD 0.07% (95%CI: 0.19-0.33); P = 0.60; I2 = 91%]. Low dose lobeglitazone (0.25 mg/d) was inferior to high dose lobeglitazone (0.5 mg/d) with regards to glycaemic efficacy with advantage of lower weight gain and edema. CONCLUSION: The current evidence makes lobeglitazone unlikely to replace pioglitazone as the preferred thiazolidinedione in T2DM.

Correlates of loneliness and dissatisfaction following SARS pandemic lockdown: Child and parent perspective.

Background Studying loneliness among children is important because it causes much social pain and is considered to be a risk factor for many mental and physical problems. Methods We did an online survey between July and September 2020 among students and their parents from a cluster of government and private schools chosen from north, south, east and west of Chandigarh. The survey consisted of child and parent versions of the Loneliness and Social Dissatisfaction Questionnaire, Parent-Child Relationship (PCR) Questionnaire and Conflict Behaviour Questionnaire SF. Parental distress was assessed using the Depression, Anxiety and Stress Scale-21. Results The majority of children and parent participants reported high loneliness and dissatisfaction among children. A significant positive association was found between children and parent reported loneliness and dissatisfaction, and between child reported PCR and parent perception of PCR. A child's appraisal of her loneliness had a significant negative association with depression among parents. Parent's perception of child loneliness and dissatisfaction was negatively associated with PCR and parental anxiety. High loner boys reported poor quality of relationship and more conflicts with their parents than girls. Children who share cordial relations with their parents had fewer conflicts and also scored low on loneliness. Conclusion These results suggest that the issue of loneliness and dissatisfaction among children has attained epidemic proportions in the Covid-19 era, and active interventions are needed to safeguard the mental health of children. Our study emphasizes the need to plan guidance strategies with a joint effort of schools and families to strengthen within family relations of children.