A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India.

BACKGROUND: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. METHODS: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. DISCUSSION: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. TRIAL REGISTRATION: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement.

Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

An Access to Androgen Excess: The Ovary Unregulated.

Hirsutism is excess terminal hair that commonly appears in a male pattern in women. It is associated with hyperandrogenemia. Ferriman-Gallwey scoring system is the most popular scoring system for evaluation, treatment and monitoring the response to therapy. Causes include PCOS, Cushing syndrome, glucocorticoid resistance, drugs, more serious conditions like androgen secreting tumour of ovaries or the adrenal gland, hyperthecosis ovarii and luteoma of pregnancy. We present a case of severe PCOS (Hyperthecosis ovarii) which mimics androgen secreting tumour from ovary in a 30- yr- old lady. This case emphasizes on the spectrum of manifestations that PCOS can come with and the importance of trans vaginal ultrasonography in diagnosing ovarian conditions and its superiority over conventional trans abdominal USG or CT scan.

Mania in Wolfram's Disease: From Bedside to Bench.

Wolfram syndrome is a relatively unexplored entity in clinical psychiatry. Historically, the discovery of a specific WFS1 gene had generated huge fanfare regarding specific genetic causations of psychiatric disorders. While the initial enthusiasm has faded now, association of Wolfram syndrome with psychiatric illnesses like schizophrenia, psychosis and suicidal behavior still remain important for understanding biological underpinnings of such disorders. We report a case of Wolfram syndrome presenting with multiple manic episodes, discuss possible genetic underpinnings for the affective symptoms and then discuss certain issues regarding management.

Proteus syndrome: A rare cause of gigantic limb.

A congenital disorder with variable manifestations, including partial gigantism of the hands and feet with hypertrophy of soles, nevi, hemihypertrophy, gynecomastia, macrocephaly and other skull abnormalities, and abdominal lipomatosis. The cause is unknown, although a genetic origin, generally of autosomal-dominant transmission, has been conjectured. Symptoms can be treated, but there is no known cure. We present the case of a young male with grotesque overgrowth of the right lower limb, splenomegaly and multiple nevi. Angiography revealed venous malformation within the limb. The findings are in conformity to the criteria for the Proteus syndrome.

Hypopituitarism following poisonous viperbite.

A 28 years old male had the history of viperbite 3 years back. He has treated in a nearby rural hospital with snake venom antiserum along with other supportive therapy. He responded and discharged from hospital within a week. Three years later he had history of fever, drowsiness which progressed to unconsciousness. On examination he was found to have scanty body hairs, smooth, shiny skin with superficial oral ulcers. Serum hormone estimation confirmed the deficiency of gonadotrophins, thyrotrophin and corticotrophin while growth hormone failed to rise >3ng/ml after insulin intolerance test. MRI brain revealed loss of pituitary mass with positive infundibular sign and filling of sella with cerebrospinal fluid. He was managed with hormone replacement therapy and recovered gradually.

A descriptive study of hyponatremia in a tertiary care hospital of Eastern India.

BACKGROUND: Hyponatremia is one of the commonest electrolyte disturbances encountered in medical wards and contributes to substantial morbidity and mortality. However, early recognition and management drastically alters prognosis. Therefore, this observational study was taken up to explore the clinical profile of hyponatremia. AIM: To assess the incidence and clinical profile of hyponatremia in medically ill patients. MATERIALS AND METHODS: This observational study was conducted in the medical ward of a tertiary care hospital from March 2010 to April 2011. All patients underwent routine hemogram, blood biochemistry, serum electrolytes, thyroid function tests, and morning serum cortisol estimation. This was followed by a plasma and urinary osmolality determination (osmometer 800 CL) as well as urinary sodium estimation. Patients were diagnosed to have syndrome of inappropriate antidiuretic hormone secretion (SIADH) if they satisfied the Bartter and Schwartz criteria. RESULTS: 201 patients (16.4%) had a serum Na < 135 meq/l. There were 126 (62.69%) male patients and 75 (37.31%) female patients. Severe hyponatremia (Na < 120 meq/l) was detected in 30 patients (2.4%). The largest group of hyponatremic patients were euvolemic [102 (50.74%)], followed by hypervolemic [54 (26.86%)] and hypovolemic [45 (22.4%)]. Sixty-six patients fulfilled the criteria for SIADH. The most common underlying predisposing factor for hyponatremia in our case series was fluid loss by vomiting/diarrhea. During the hospital stay, 13.5% (15/201) hyponatremic patients died, while the corresponding figure in normonatremic patients was 8.5% (87/1020). CONCLUSION: The incidence of hyponatremia in our series was higher than values mostly reported in western literature. Euvolemic hyponatremia was the most common type, a significant fraction of which is SIADH.

Prevalence of diabetic foot ulcers in newly diagnosed diabetes mellitus patients.

Foot ulcer is one of the most common and dreadest complication of diabetes mellitus.This is also a frequent cause of hospitalisation and disability. Most of the patients with diabetic foot ulcers living in developing countries present to healthcare facilities fairly late with advanced foot ulcers because of poor economic status, inadequate knowledge of self-care, sociocultural reasons and poor and inadequate diabetes healthcare. To determine the prevalence of diabetic foot ulcers amongst the newly diagnosed diabetes mellitus patients (n = 1674) a cross-sectional study was carried out during the period January 2010 to January 2011 in the department of medicine, NRS Medical College, Kolkata. Diabetic foot ulcers were found in 4.54% newly diagnosed diabetes mellitus patients. Neuropathic type of foot ulcer was present in 46.06% of patients (52.5% in male and 38.88% in female). Ischaemic type of foot ulcer was present in 19.74% of patients (22.5% in male and in 16.66% females). Neuroischaemic type of foot ulcer was present in 34.2% of patients (25% in males and 44.44% in females). Neuropathy occurred most frequently either singly or with peripheral vascular disease. General awareness about the disease, early diagnosis and proper management will prevent this dreaded complication.

Complications of hypertension as encountered by primary care physician.

Hypertension is a common clinical problem with great implications for public health. It is a silent killer and often remains asymptomatic. So regular BP check-up is a must. Complications of untreated hypertension include ventricular hypertrophy, heart failure and accelerated atherosclerosis, cerebrovascular disease and stroke, renal failure and retinopathy. Primary care physicians have immense duty to perform in this regard because they are the first to encounter them in various stages of the disease. Hypertension can present per se or in emergencies (as in crisis) or in disguise of a complication (like anaemia and renal failure). Control of hypertension and delaying the development of complications should be their first goal. Lastly, some hypertensives with complications may require referral to advanced centres.