Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

BACKGROUND: Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. METHODS: A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. RESULTS: A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. CONCLUSION: A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.

BACKGROUND: The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α1 receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin. MATERIALS AND METHODS: A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values. RESULTS: Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP. CONCLUSION: Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.

Comparative clinical efficacy and safety of insulin glargine 300 U/ml (Toujeo) versus insulin glargine 100 U/ml in type 2 diabetes and type 1 diabetes: A systematic literature review and meta-analysis.

AIM: To compare the clinical efficacy and safety of glargine-U100 (Lantus/Gla-100) with glargine-U300 (Toujeo/Gla-300) in adult patients with type 2 diabetes (T2D) and type 1 diabetes (T1D). MATERIALS AND METHODS: A literature search on Gla-300/Gla-100 in diabetes management was conducted using the MEDLINE/Embase/Cochrane databases from inception to 10 January 2021. Eligible studies considered for inclusion were parallel-design, randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. The random-effects model was applied for interpretation of the results. RESULTS: Of 5348 records screened, 592 were assessed for eligibility and 15 RCTs were considered for data extraction and meta-analysis (T2D [N = 10; n = 7082]; T1D [N = 5; n = 2222]). In patients with T1D, all safety parameters were comparable between Gla-100 and Gla-300. In T2D, statistically significant differences were observed in favour of Gla-300 over Gla-100 for nocturnal and total hypoglycaemia. For efficacy parameters, a statistically and clinically significant difference favouring Gla-100 in basal insulin dose requirement was observed for both T2D and T1D. Change in HbA1c showed a statistically but not clinically significant reduction with Gla-100 compared with Gla-300 in T1D. Statistically significant but clinically less relevant differences favoured Gla-300 for control of body weight in T1D and T2D and Gla-100 for fasting blood glucose in T2D. CONCLUSIONS: Gla-100 and Gla-300 had comparable efficacy and safety profiles in both T1D and T2D populations. Gla-300 showed a lower risk of nocturnal and total hypoglycaemia, significant in insulin-experienced/exposed patients with T2D. Patients on Gla-300 required significantly more units of insulin daily than the Gla-100 group to achieve equivalent efficacy.

Prevalence of Pancreatic Exocrine Insufficiency among Patients with Diabetes Mellitus in India.

AIMS: We aimed to assess the prevalence of pancreatic exocrine insufficiency (PEI) in Indian patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a unique diagnostic criterion. METHODS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. RESULTS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. CONCLUSIONS: Pancreatic exocrine insufficiency (PEI) was found to be prevalent in nearly one-fourth of Indian patients with diabetes, using composite diagnostic criteria.

Indian Reality of Clinical Practice and Patient Profile in Diabetes Care: Lessons from the IMPACT survey.

India shoulders a heavy burden of diabetes mellitus (DM), the management of which is suboptimal globally.& Objectives: Insulin Management: Practical Aspects in Choice of Therapy (IMPACT) survey was designed to gain insight into the ground (in-clinic) reality of DM management by physicians in India. METHODS: A survey consisting of 12 multiple-choice questions was conducted by SurveyMonkey® , focusing on practice profile, patient profile, and other aspects of DM management. RESULTS: The survey included 2424 physicians. Majority of them were general physicians (58.5%) followed by diabetologists (31.1%). Most (49.2%) of the respondents specified that the ideal time for a DM consultation is 15 min. However, 73.4% of them provided consultation of <10& min because of heavy patient load. Nearly half of the respondents reported that their patients consumed a diet with carbohydrate content of 60% to 80%, and 79.4% of them admitted that <50% of their patients adhered to dietary advice. About 73.5% of the respondents believed controlling fasting plasma glucose (FPG) level alone would not adequately control postprandial plasma glucose (PPG) level, and 93.0% of them preferred an insulin therapy at the initiation that controls both FPG and PPG levels. CONCLUSION: Limited consultation time, high-carbohydrate diet, and a need for choosing insulin regimens that provide control for both PPG and FPG levels are some ground realities of DM management in India. These realities need to be factored in while choosing treatment options to achieve the desired glycemic control and improve the status of diabetes care.

Do we need to change the Patient Indications for Trimetazidine after ATPCI?

The results of the ATPCI (efficAcy and safety of Trimetazidine in patients with angina pectoris treated by Percutaneous Coronary Intervention) study showed no significant difference in the incidence of primary endpoint events between trimetazidine and the placebo group in angina patients who recently underwent percutaneous coronary intervention. The study had limitations specific to the design and selection of the target patient population. However, safety outcomes for trimetazidine were reconfirmed in this study. In this article, we discuss the limitations of study design, patient inclusion criteria and their implications in routine practice. We have also dissected the evidence to tweeze out patient groups who are likely to benefit from trimetazidine treatment.

New and Unique Clusters of Type 2 Diabetes Identified in Indians.

Type 2 diabetes (T2D), the most common form of diabetes, is recognized as being a heterogenous disorder, and presents a universal threat to health. In T2D, the pathophysiology and phenotype differ significantly by ethnicity, particularly among Asian Indians, who are known to have the 'Asian Indian phenotype', which makes them more susceptible to develop T2D than white Caucasians. The recent subclassification of T2D into different subtypes or clusters, which behave differently with respect to clinical presentation and risk of developing complications is a remarkable development. Five unique "clusters" of individuals with diabetes were described in the Scandinavian population [Severe Autoimmune Diabetes (SAID), Severe Insulin Deficient Diabetes (SIDD), Severe Insulin Resistant Diabetes (SIRD), Mild Obesity-related Diabetes (MOD) and Mild Age-Related Diabetes (MARD)]. For the first time in India, identification of clusters of diabetes was done on 19,084 individuals with T2D, using 8 clinically relevant variables (age at diagnosis, BMI, waist circumference, HbA1c, triglycerides, HDL cholesterol and fasting and stimulated C-peptide). Four replicable clusters were identified [SIDD, MARD, IROD (Insulin Resistant Obese Diabetes) and CIRDD (Combined Insulin Resistant and Deficient Diabetes)], two of which were unique to the Indian population (IROD and CIRDD). Clustering of T2D helps i) to accurately subclassify diabetes into different subtypes, ii) plan therapies based on the pathophysiology, iii) predict prognosis and prevent diabetic complications and iv) helps in our approach to precision diabetes. Further studies would help us to refine the usefulness of these clusters of T2D particularly in the Indian population, with respect to selection of appropriate therapies and hopefully in the prevention of complications of diabetes.

Management of Hyperglycemia in COVID-19 and Post-COVID-19 Syndrome - Proposed Guidelines for India.

SARS-CoV-2 virus spread rapidly all over the globe in 2020 and the second wave has taken our nation, India by storm. The pandemic has posed unique challenges in people with metabolic disorders, including diabetes, hypertension, obesity, pulmonary, cardiovascular, kidney and non-alcoholic fatty liver disease. Uncontrolled diabetes, in conjunction with endocrine, inflammatory and metabolic effects of the infection itself has made management of hyperglycemia in COVID-19 infection particularly challenging. Furthermore, the post-COVID-19 syndrome has also emerged as a sequela in COVID-19 survivors, increasing the risk of death, complications and adding further burden on the health care system. With more than a year of experience, we have gained substantial insight; and now provide practical recommendations on the management of hyperglycemia in COVID-19 as well as post COVID-19 syndrome.

COVID-19 Care in India: Evolving Paradigms from Public Health to Critical Care.

Covid-19 pandemic in India has rapidly grown though we have a low case fatality rate, high recovery rate and large population is asymptomatic or presymptomatic. Public health measures to close the tap across the country need hypervigilance and follow simple dictum of aggressive testing, tracing and isolation. The covid cases need an early diagnosis with treat and care model. Most can be managed with home isolation under telemedicine supervision with oxygen saturation screening by a simple six minute walk test. Hospitalised cases have emerging evidence in different therapies from antivirals, steroids, immunologic to heparins but high flow oxygen, prone position and supportive care remains the cornerstone in critical care with nursing and nutrition. Vaccine research is ongoing but currently only social vaccine can mitigate the pandemic. Covid appropriate behaviour of Masking, sanitisation and physical distancing with immune modulating behaviour like adequate sleep, digital detox for two hour and clean well ventilated environment is the key with breathing exercises including yoga and positive mental health and avoidance of crowds the only vaccine to live with covid -19 today.

Physician Burnout: Cause and Prevention Strategies.

Ongoing evolution in healthcare places physicians under an ever-increasing pressure to consistently perform at a higher level, leading to a significant number of physicians including those in training feeling "burnt-out". Burnout is a result of interplay between personal charateristics and environmental factors. Unadressed physician burnout negatively affects the individual, work environment and most importantly patient care. Individual and environmenal changes are needed to assess and effectively manage burnout. Stigma and fear of professional consequences, especially among regional doctors appears to be an important barrier to access services and address burnout. There is an ever increasing need to expand the Triple Aim (enhancing patient experience, improving population health, and reducing costs) to a Quadruple Aim that goal of improving the work life of health care providers, including clinicians and staff.

Prognostic Factors for Adverse Outcomes in COVID-19 Infection.

Whilst COVID-19 infection generally run a mild course in up to 80% of those affected, a number of pre-existing co-morbidities determine the severity of infection and the outcome in an individual patient. The most important of these co-morbidities that have consistently emerged in studies from across the globe, are the patients age and sex. Other important co-morbidities that adversely affect outcomes include pre-existing diabetes, obesity, hypertension, chronic lung disease and malignancy. This comprehensive review discusses the impact of these co-morbidities and the role of laboratory predictors of poor patient outcomes.

COVID 19: Diabetes and Obesity API-ICP Recommendations.

Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.

Hydroxychloroquine for COVID-19: What is our Current State of Knowledge?

Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.

Risk Benefit Analysis in Reference to use of LMWH in COVID-19.

Venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) are frequent cardiovascular and/or respiratory complications among hospitalized patients of COVID-19 infection. A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, and the application of heparin in COVID-19 has been assessed and recommended with some expert consensus because of the risk of DIC and venous thromboembolism. However, "Risk Benefit Analysis" on the aspect of safety in using low molecular weight heparin (LMWH) in COVID-19 patients for thrombosis prophylaxis has been explained below with a few case studies and detailed information from various clinical evidence. COVID-19 infection has been associated with inflammation and a prothrombotic state, with increase in fibrin, fibrin degradation products, fibrinogen, and D-dimers. Heparin treatment including unfractionated and low molecular weight heparin appears to be associated with better prognosis in severe COVID-19 patients with coagulopathy. Major studies since the onset of this pandemic, found better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer, by approaching thrombosis prophylaxis with LMWH.

Thyro-weight: Unlocking the Link between Thyroid Disorders and Weight.

Thyroid hormone is an important determinant of energy expenditure and contributes to appetite regulation, while hormones and cytokines from the adipose tissue act on the CNS to inform on the quantity of energy stores. A continuous interaction between the thyroid hormone and regulatory mechanisms localized in adipose tissue and brain is important for human body weight control and maintenance of optimal energy balance. Direct effects on ATP utilization are a result of thyroid hormone's actions on metabolic cycles and increased cell membrane ion permeability. However, the majority of thyroid hormone induced energy expenditure is thought to be a result of indirect effects, which, in turn, increase capacity for energy expenditure. This review discusses the direct actions of thyroid hormone on energy expenditure, and places special emphasis on the indirect actions of thyroid hormone, which include mitochondrial biogenesis and reduced metabolic efficiency through mitochondrial uncoupling mechanisms.

Efficacy of SGLT2 Inhibitors as the Fifth Drug in the Management of Type 2 Diabetes Mellitus in Asian Indians not Controlled with at least 4 Oral Antidiabetic Drugs.

AIM: To evaluate the efficacy of SGLT2 inhibitors as an add-on therapy along with stricter lifestyle modification in Asian Indian type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). METHODOLOGY: A retrospective analysis of data of 808 T2DM patients being treated with an SGLT2 inhibitor (Dapagliflozin, Empagliflozin or Canagliflozin) as an add-on drug in patients with inadequate glycemic control despite receiving optimum doses of at least any four OADs(metformin, sulphonylureas, pioglitazone, DPP4 Inhibitors, alpha-Glucosidase Inhibitors) and who preferred not to initiate insulin. RESULTS: The average age of the patients included was 51.63 years (SD ± 9.88). 57.7% were males. Average weight was 81.95±16.08 kg. Mean duration of diabetes was 34.08±39.04 months. The mean baseline fasting plasma glucose was 198.21 ± 38.21 mg/dl and mean post prandial plasma glucose was 264.22 ± 45.22 mg/ dl. The baseline HbA1c was 8.92 ± 1.47 %. Total 87.4 % of the cases responded to addition of SGLT2 inhibitors during a mean follow-up period of 6 months. The fasting plasma glucose (FBS) was reduced by -63.65 ± 19.93 mg/dl to a mean FBS of 134.57 ± 33.65 mg/dl (P=0.001). The post prandial plasma glucose (PPBS) was reduced by -79.28 ± 23.57 mg/dl to a mean PPBS of 184.94 ± 38.34 mg/dl (P=0.001). The mean HbA1c reduced significantly by -1.63 ± 0.99 % (P= 0.001). The mean weight reduction at 6 months of therapy was -3.03± 01.84 kg that is 3.8 % decrease from baseline (p=0.001).The response in age group < 55 years was 90.9 %, whereas in ≥55 years, it was 82.2% (p=0.001). The males responded more (91.0%) compared to females (82.5%) (p=0.001). Those with BMI < 23.5 kg/ m2 had marginally higher but insignificant response of 93.0% as compared to 87.1% in patients with high a BMI (≥23.5 kg/m2) (p=0.253). Patients with < 5years duration of diabetes responded better (91.8%) as compared to patients with a ≥ 5 years of diabetes (85.4%). CONCLUSION: SGLT2 inhibitors are effective in achieving desired glycemic goals even when used as a fifth add-on drug along with strict lifestyle modification in patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). SGLT2 inhibitors can be effectively used at any stage of diabetes.

Role and Relevance of Blood Pressure Variability in Hypertension Related Co-morbidities.

Despite maintaining mean blood pressure at optimal levels, cardiovascular complications still occur in hypertensive patients. Blood pressure variability (BPV) has been implicated as a prominent factor responsible for incurring this additional risk. In this review we attempted to generate a consensus on the importance of BPV in the hypertension management and to evaluate different therapeutic options available to reduce BPV. Panel comprising of 11 leading experts from India in different areas of clinical practice (including nephrology, diabetes and endocrinology, cardiology, and critical care medicine) was convened. The board reviewed up to date literature on BPV, shared personal experiences from their clinical practice, and debated their opinions on the significance of BPV in hypertension management and also on various therapeutic options available to control it. The reviewers agreed that BPV is frequently observed in hypertensive individuals and it is a critical factor in hypertension management. Blood pressure variability can be measured by ambulatory blood pressure monitoring, home blood pressure monitoring, and office blood pressure monitoring. Members concurred that variations in blood pressure that are 10 standard deviations above the mean blood pressure should be considered as pathologically significant and such variations should be reduced using pharmacological therapies. The board opined that Angiotensin II Receptor Blockers,Calcium Channel Blockers etc such as Olmesartan, Nifedipine can be used to reduce BPV. As a way forward, the panel recommends to bridge the evidence gap that establishes a possible direct relationship between BPV and cardiovascular complications. Blood pressure variability has paramount role in the current hypertension management scenario. To reduce disease burden and increase quality of life of hypertensive individuals, physicians should consider lowering BPV along with physiological BP levels.