Background: Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease have been inconclusive. Objective: The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease. Methods: We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease. Results: Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer’s Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs. Conclusions: There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes. Trial Registration: PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421

Oral iron is the mainstay of treating iron deficiency anemia. Recent studies indicate better fractional iron absorption with alternate day supplementation. However, the optimal supplementation strategy is unclear. We compared effectiveness of daily versus alternate day supplementation of oral iron for treatment of iron deficiency anemia. This double blind, active control, randomized controlled trial was conducted on two hundred adults having hemoglobin 10 g/dL or less with microcytic hypochromic anemia and/or serum ferritin below 50 ng/mL. They were randomized to receive either two Ferrous sulfate tablets containing 60 mg elemental iron (120 mg total) on alternate days or single tablet of 60 mg elemental iron daily for 8 weeks. Primary outcome was mean change in hemoglobin at week 8 from baseline. Mean hemoglobin was 6.53 (± 1.89) and 6.68 (± 1.89) g/dL in the alternate day and daily arms respectively. Mean change in hemoglobin was + 1.05 ± 1.34 g/dL in alternate day arm and + 1.36 ± 1.51 g/dL in daily arm (p = 0.47) at week 8. There were no statistically significant differences between the arms with respect to any secondary outcome. There is no significant difference between alternate day and daily iron administration in improving hemoglobin. Randomized controlled trials enrolling more participants for longer periods of supplementation and evaluating clinically relevant outcomes like change in hemoglobin may be useful in identifying the ideal dosing strategy.Trial Registration: Clinical Trial Registry of India (CTRI/2019/01/017169).

BackgroundConcurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited.MethodologyThis was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA.ResultsThere were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache and arthralgia were common. Normal haemoglobin, significant thrombocytopenia, transaminitis and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus.ConclusionDengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leucocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost.

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer’s disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.

Background: While several parameters have emerged as predictors of prognosis of COVID-19, a simple clinical score at baseline might help early risk stratification. We determined the ability of National Early Warning Score 2 (NEWS2) to predict poor outcomes among adults with COVID-19. Methods: A prospective study was conducted on 399 hospitalised adults with confirmed SARS-CoV-2 infection between August and December 2020. Baseline NEWS2 score was determined. Primary outcome was poor outcomes defined as need for mechanical ventilation or death within 28 days. The sensitivity, specificity and Area under the curve were determined for NEWS2 scores of 5 and 6. Results: Mean age of patients was 55.5 ± 14.8 years and 275 of 399 (68.9%) were male. Overall mortality was 3.8% and 7.5% had poor outcomes. Median (interquartile range) NEWS2 score at admission was 2 (0–6). Sensitivity and specificity of NEWS 2 of 5 or more in predicting poor outcomes was 93.3% (95% CI: 76.5–98.8) and 70.7% (95% CI: 65.7–75.3) respectively [area under curve 0.88 (95% CI: 0.847–0.927)]. Age, baseline pulse rate, baseline oxygen saturation, need for supplemental oxygen and ARDS on chest X ray were independently associated with poor outcomes. Conclusions: NEWS2 score of 5 or more at admission predicts poor outcomes in patients with COVID-19 with good sensitivity and can easily be applied for risk stratification at baseline. Further studies are needed in the Indian setting to validate this simple score and recommend widespread use.

As it is increasingly being reported from India, we carried out a prospective study of patients with culture-proven melioidosis from south India, examining clinical, laboratory features, epidemiological data, risk factors, treatments, outcomes at three and six months, and factors associated with mortality. Between 2014 and 2018, 31 cases were identified. Diabetes (83.9%) and alcohol abuse (58.1%) were common risk factors. Musculoskeletal, skin and soft tissue manifestations together constituted 48.4% of presentations, while 29% had pneumonia. During the intensive phase, 74.2% received one of three recommended antibiotic regimes, but 51.6% did not receive continuation treatment. Pneumonia and lack of continuation treatment were independently associated with a high mortality of 25.8%. Hot spots for melioidosis exist in India, and there is considerable diversity of presentation, including skin, soft tissue, musculoskeletal and neurological involvement. High rates of bacteraemia are shown.