Comparison of the efficacy and safety of rapid-acting insulin analogs, lispro versus aspart, in the treatment of diabetes: a systematic review of randomized controlled trials.

INTRODUCTION: We evaluated a potential move from one rapid-acting insulin analog to another, or their biosimilars, to aid better and faster decisions for diabetes management. METHODS: A systematic literature review was performed according to PRISMA reporting guidelines. The MEDLINE/EMBASE/COCHRANE databases were searched for randomized control trials (RCTs) comparing aspart/lispro in type-1 (T1D) and type-2 (T2D) diabetes. The methodological quality of the included studies was assessed using the Cochrane Collaboration's risk of bias assessment criteria. RESULTS: Of the 753 records retrieved, the six selected efficacy/safety RCTs and the additional three hand-searched pharmacokinetics/pharmacodynamics RCTs showed some heterogeneity in the presentation of the continuous variables; however, collectively, the outcomes demonstrated that lispro and aspart had comparable efficacy and safety in adult patients with T1D and T2D. Both treatments yielded a similar decrease in glycated hemoglobin (HbA1c) and had similar dosing and weight changes, with similar treatment-emergent adverse events (TEAE) and serious adverse event (SAE) reporting, similar hypoglycemic episodes in both T1D and T2D populations, and no clinically significant differences for hyperglycemia, occlusions or other infusion site/set complications. CONCLUSIONS: Aspart and lispro demonstrate comparative safety and efficacy in patients with T1D/T2D. Since both are deemed equally suitable for controlling prandial glycemic excursions and both have similar safety attributes, they may be used interchangeably in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42023376793.

Clinical effects of a yoga-based intervention for patients with schizophrenia - A six-month randomized controlled trial.

BACKGROUND: Yoga has shown promise as an add-on therapy for patients with schizophrenia. However, most studies have been short-term, with methodological limitations. METHODS: We conducted a six-month parallel-group randomized-controlled trial (with rater blinding) to evaluate the effectiveness of a yoga-based intervention in improving symptoms and quality of life in patients with schizophrenia. We recruited 110 patients from an urban tertiary hospital and a semi-urban community centre who met DSM 5 criteria for schizophrenia and were on stable medication for at least six weeks. Participants were randomly assigned to either yoga add-on therapy (YT) or treatment-as-usual (TAU) groups. Clinical assessments were conducted at baseline and at one, three and six months. The primary outcome was changes in positive/negative symptom scores and secondary outcomes included changes in quality of life, perceived stress and socio-occupational functioning. RESULTS: Intention to treat analysis with a longitudinal mixed model approach revealed a significant group-by-time interaction with the YT group showing medium effect improvements in negative symptoms (η2p = 0.06) and small effect improvements in positive symptoms (η2p = 0.012), WHOQOL-BREF quality of life [psychological well-being (η2p = 0.015) and environmental health (η2p = 0.048)] when compared to TAU. The patients successfully learned and performed yoga practices without reporting any significant adverse effects. DISCUSSION: Our findings suggest that yoga-based intervention may be a valuable adjuvant therapy for medication-stabilized patients with schizophrenia, especially in ameliorating negative symptoms and enhancing quality of life. Future controlled trials, including active physical interventions, are crucial to validate yoga's efficacy, optimize clinical use, and elucidate underlying mechanisms.

A unique case of Salmonella typhi peritonitis in a CAPD patient.

Peritonitis is the Achilles heel of continuous ambulatory peritoneal dialysis (CAPD) leading to significant morbidity and mortality. We report a 57 year old lady with coronary artery disease, pulmonary hypertension and diabetic kidney disease on CAPD for four years, who presented with Salmonella typhi peritonitis. As response to intraperitoneal antibiotics was unsatisfactory, the peritoneal dialysis catheter was removed after five days and shifted to maintenance hemodialysis. Following resolution of infection after a prolonged course of intravenous antibiotics, a swan neck catheter was re-implanted after eight weeks. There was peritoneal membrane failure and hence she continued on hemodialysis but she succumbed.

MAO-B Inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a Neuroprotective Agent Against Alzheimer's Disease.

Chalcones (trans-1,3-diphenyl-2-propen-1-ones) form simple chemical structures that act as precursors for the biogenesis of flavonoids. These are distributed in plants and have two aromatic or heteroaromatic rings connected by a three-carbon α, ß-unsaturated carbonyl group. Considering the importance of chalcones as monoamine oxidase and acetylcholinesterase inhibitors, the study was designed as a comprehensive and systematic analysis to evaluate the pharmacological activities leading to the formation of drug molecules against Alzheimer's disease (AD). Based on our previous research, 11 indolyl chalcones (IC1-IC11) were synthesised and investigated for MAO-B inhibitory activity. The inhibitory potential was evaluated based on binding and reversibility studies using purified enzymes. The active and most promising molecule, (2E)-3-(4-bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one (IC9), also found predominant acetylcholinesterase inhibition and hence it was found dual acting in vitro. Based on this, the molecule IC9 was further subjected to cell line studies to further explore its role as a neuroprotective agent against neuronal degeneration, one of the main contributing parameters related to AD.

Effects of a six-month yoga intervention on the immune-inflammatory pathway in antipsychotic-stabilized schizophrenia patients: A randomized controlled trial.

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder for which several etiopathological theories have been proposed, one of the prominent ones being immune dysfunction. Recent studies on yoga as an add-on therapy have shown improvement in negative symptoms, cognition, and quality of life in schizophrenia patients. However, the biological mechanism/s of action of yoga in schizophrenia are not clear. The current study was aimed at exploring the effects of long-term (6 months) add-on yoga therapy on the immune inflammatory pathway in schizophrenia patients. METHODS: Sixty schizophrenia patients were randomized to add-on yoga therapy (YT=30) and treatment-as-usual (TAU=30) groups of which 21 patients in YT and 20 in TAU group completed the study. Blood samples and clinical assessments were obtained at baseline and at the end of 6 months. The plasma levels of nine cytokines (IL-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ, and TNF-α) were quantified using multiplex suspension array. The clinical assessments included SAPS, SANS, BPRS, PSS, CGI, SOFS and WHOQUOL-BREF. RESULTS: Patients in the yoga group showed significant reductions in plasma TNF-α (Z = 2.99, p = 0.003) and IL-5 levels (Z = 2.20, p = 0.03) and greater clinical improvements in SAPS, SANS, PSS, and SOFS scores as compared to TAU group. Further, plasma TNF-α levels exhibited a positive correlation with negative symptoms (rs =0.45, p = 0.02) and socio-occupational functioning (rs =0.61, p = 0.002) in the YT group. CONCLUSIONS: The findings of the study suggest that improvements in schizophrenia psychopathology with yoga interventions are associated with immuno-modulatory effects.

Biosimilars and interchangeable biosimilars: facts every prescriber, payor, and patient should know. Insulins perspective.

INTRODUCTION: For many of the 537 million adults living now with diabetes, the cost of insulin is becoming prohibitive as the insulin prices have tripled between 2002-2013. Globally, the direct annual cost of healthcare expenditure due to diabetes will soon be US$1 Trillion. Biosimilars provide access to high-quality, affordable biologic therapy that is otherwise inaccessible due to the high costs of original biologics. AREAS COVERED: A primer to the development of biosimilars shows comparable structural and analytical characterization to the original biologics (e.g. insulins), with no clinically significant or meaningful differences in efficacy and safety. 'Interchangeability' status, a regulatory designation by the US FDA, bestowed to some biosimilars, enables confidence in high-quality, bio-equivalent biosimilar of insulin with key global approvals. This can allow rapid uptake of biosimilars by the prescribers, formulary decision-makers, and payors. Biocon-Viatris's biosimilar Insulin Glargine (Semglee®) is the first interchangeable biosimilar insulin approved by the US FDA. EXPERT OPINION: The 'interchangeable' status can prompt faster and wider uptake of insulin biosimilars and keep the insulin expenditure under control, especially for patients who otherwise practice non-adherence or rationing of life-saving insulin. Education, support, and awareness can ensure that interchangeable biosimilars gain wider acceptance.

Role of Cyclosporine (CsA) in Immuno-dermatological Conditions.

Cyclosporine (CsA) is a calcineurin inhibitor that acts selectively on T cells. It has been used in dermatology since 1997 for its US Food and Drug Administration indication of psoriasis and off-label for various other inflammatory skin conditions, including atopic dermatitis, alopecia areata, urticaria, lichen planus and many others in pediatric, adults as well as in pregnant women. However, clinicians' preferences for management differ, which may have a bearing on the treatment selection. Hence, the purpose of this review is to outline the role of CsA in various skin conditions through consensus statement from six national experts in the field of dermatology.

Thermodynamic analysis of single slope solar still using graphite plates and block magnets at seasonal climatic conditions.

In this research, the thermodynamic (energy and exergy) analysis of a single slope solar still using graphite plates and block magnets (GPBMSS) was investigated during summer and winter climatic conditions of Coimbatore city (latitude: 11°01'68''N and longitude: 76°95'58''E), in India, 2019. The results observed in GPBMSS were compared with a conventional solar still (CSS) under the same climatic conditions. The outcomes observed that the hourly productivity in GPBMSS was 19.6% and 22.8% higher in summer and winter days, respectively, when compared to CSS. The cumulative productivity in GPBMSS was found to be about 3.93 kg/m2 and 3.56 kg/m2 respectively, for 12 h observations during summer and winter days. Furthermore, the energy and exergy efficiencies of GPBMSS were substantially improved by 20.6% and 18.1% when compared to CSS during summer days. Similarly, the energy and exergy efficiencies of GPBMSS were increased by 18 and 19% compared to CSS in winter days. In addition, the maximum basin exergy destruction was observed in CSS compared to other solar still components. The results observed that the heat storage ability of the graphite plates and water magnetization in GPBMSS greatly decreased the exergy destructions. Finally, the water quality analysis proved that the distillate collected from both GPBMSS and CSS satisfied the requirements recommended by the Bureau of Indian Standards.

Impact of Pharmacological and Non-Pharmacological Modulators on Dendritic Spines Structure and Functions in Brain.

Dendritic spines are small, thin, hair-like protrusions found on the dendritic processes of neurons. They serve as independent compartments providing large amplitudes of Ca2+ signals to achieve synaptic plasticity, provide sites for newer synapses, facilitate learning and memory. One of the common and severe complication of neurodegenerative disease is cognitive impairment, which is said to be closely associated with spine pathologies viz., decreased in spine density, spine length, spine volume, spine size etc. Many treatments targeting neurological diseases have shown to improve the spine structure and distribution. However, concise data on the various modulators of dendritic spines are imperative and a need of the hour. Hence, in this review we made an attempt to consolidate the effects of various pharmacological (cholinergic, glutamatergic, GABAergic, serotonergic, adrenergic, and dopaminergic agents) and non-pharmacological modulators (dietary interventions, enriched environment, yoga and meditation) on dendritic spines structure and functions. These data suggest that both the pharmacological and non-pharmacological modulators produced significant improvement in dendritic spine structure and functions and in turn reversing the pathologies underlying neurodegeneration. Intriguingly, the non-pharmacological approaches have shown to improve intellectual performances both in preclinical and clinical platforms, but still more technology-based evidence needs to be studied. Thus, we conclude that a combination of pharmacological and non-pharmacological intervention may restore cognitive performance synergistically via improving dendritic spine number and functions in various neurological disorders.

Complications after bariatric surgery: A multicentric study of 11,568 patients from Indian bariatric surgery outcomes reporting group.

BACKGROUND: Complications after bariatric surgery are not uncommon occurrences that influence the choice of operations both by patients and by surgeons. Complications may be classified as intra-operative, early (<30 days post-operatively) or late (beyond 30 days). The prevalence of complications is influenced by the sample size, surgeon's experience and length and percentage of follow-up. There are no multicentric reports of post-bariatric complications from India. OBJECTIVES: To examine the various complications after different bariatric operations that currently performed in India. MATERIALS AND METHODS: A scientific committee designed a questionnaire to examine the post-bariatric surgery complications during a fixed time period in India. Data requested included demographic data, co-morbidities, type of procedure, complications, investigations and management of complications. This questionnaire was sent to all centres where bariatric surgery is performed in India. Data collected were reviewed, were analysed and are presented. RESULTS: Twenty-four centres responded with a report on 11,568 bariatric procedures. These included 4776 (41.3%) sleeve gastrectomy (SG), 3187 (27.5%) one anastomosis gastric bypass (OAGB), 2993 (25.9%) Roux-en-Y gastric bypass (RYGB) and 612 (5.3%) other procedures. Total reported complications were 363 (3.13%). Post-operative bleeding (0.75%) and nutritional deficiency (0.75%) were the two most common complications. Leaks (P = 0.009) and gastro-oesophageal reflux disease (P = 0.019) were significantly higher in SG, marginal ulcers in OAGB (P = 0.000), intestinal obstruction in RYGB (P = 0.001) and nutritional complications in other procedures (P = 0.000). Overall, the percentage of complications was higher in 'other' procedures (6.05%, P = 0.000). There were 18 (0.16%) reported mortalities. CONCLUSIONS: The post-bariatric composite complication rate from the 24 participating centres in this study from India is at par with the published data. Aggressive post-bariatric follow-up is required to improve nutritional outcomes.

Ophthatome™: an integrated knowledgebase of ophthalmic diseases for translating vision research into the clinic.

BACKGROUND: Medical big data analytics has revolutionized the human healthcare system by introducing processes that facilitate rationale clinical decision making, predictive or prognostic modelling of the disease progression and management, disease surveillance, overall impact on public health and research. Although, the electronic medical records (EMR) system is the digital storehouse of rich medical data of a large patient cohort collected over many years, the data lack sufficient structure to be of clinical value for applying deep learning methods and advanced analytics to improve disease management at an individual patient level or for the discipline in general. Ophthatome™ captures data contained in retrospective electronic medical records between September 2012 and January 2018 to facilitate translational vision research through a knowledgebase of ophthalmic diseases. METHODS: The electronic medical records data from Narayana Nethralaya ophthalmic hospital recorded in the MS-SQL database was mapped and programmatically transferred to MySQL. The captured data was manually curated to preserve data integrity and accuracy. The data was stored in MySQL database management system for ease of visualization, advanced search functions and other knowledgebase applications. RESULTS: Ophthatome™ is a comprehensive and accurate knowledgebase of ophthalmic diseases containing curated clinical, treatment and imaging data of 581,466 ophthalmic subjects from the Indian population, recorded between September 2012 and January 2018. Ophthatome™ provides filters and Boolean searches with operators and modifiers that allow selection of specific cohorts covering 524 distinct ophthalmic disease types and 1800 disease sub-types across 35 different anatomical regions of the eye. The availability of longitudinal data for about 300,000 subjects provides additional opportunity to perform clinical research on disease progression and management including drug responses and management outcomes. The knowledgebase captures ophthalmic diseases in a genetically diverse population providing opportunity to study genetic and environmental factors contributing to or influencing ophthalmic diseases. CONCLUSION: Ophthatome™ will accelerate clinical, genomic, pharmacogenomic and advanced translational research in ophthalmology and vision sciences.

Obesity and Metabolic Surgery Society of India (OSSI) Recommendations for Bariatric and Metabolic Surgery Practice During the COVID-19 Pandemic.

Bariatric and metabolic surgery (BMS), the only effective option for patients with obesity with or without comorbidities, has been stopped temporarily due to the ongoing novel corona virus disease (COVID-19) pandemic. However, there has been a recent change in the governmental strategy of dealing with this virus from 'Stay at Home' to 'Stay Alert' in many countries including India. A host of health services including elective surgeries are being resumed. In view of the possibility of resumption of BMS in near future, Obesity and Metabolic Surgery Society of India (OSSI) constituted a committee of experienced surgeons to give recommendations about the requirements as well as precautions to be taken to restart BMS with emphasis on safe delivery and high-quality care.

Influence of Asian Ethnicities on Short- and Mid-term Outcomes Following Laparoscopic Sleeve Gastrectomy.

PURPOSE: Prevalence of obesity in Asia has been on the increasing trend, with corresponding increase in utilisation of bariatric surgery. The objective of this study was to examine differences in weight loss outcomes following bariatric surgery between Asian ethnicities. MATERIALS AND METHODS: A retrospective database review was conducted of patients undergoing primary laparoscopic sleeve gastrectomy between 2009 and 2013 in 14 centres from Singapore, Malaysia, Taiwan, Hong Kong, Japan, Korea, India, Australia, Switzerland, and the USA. All patients with available follow-up data at 12 months and 36 months post-surgery were included in this study. Outcome measures used were percentage excess weight loss (%EWL) and percentage total weight loss (%TWL). Differences in outcomes between ethnicities were analysed after adjusting for age, gender, baseline body mass index (BMI), and presence of diabetes. RESULTS: The study population (n = 2150) consisted of 1122 Chinese, 187 Malays, 309 Indians, 67 Japanese, 259 Koreans, and 206 Caucasians. 67.1% were female and 32.9% were male. Mean age was 37.1 ± 11.2 years. Mean pre-operative BMI was 40.7 ± 8.1 kg/m2. With the Caucasian population as reference, Japanese had the best %TWL (3.90, 95% CI 1.16-6.63, p < 0.05) and %EWL (18.55, 95% CI 10.33-26.77, p < 0.05) while the Malays had the worst outcomes. Both Chinese and Koreans had better %EWL but worse %TWL as compared to Caucasians and there were no significant differences with the Indian study group. CONCLUSION: There are differences in weight loss outcomes following bariatric surgery between Asian ethnicities.

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.

Laparoscopic Division of Median Arcuate Ligament for the Celiac Axis Compression Syndrome-Two Case Reports with Review of Literature.

Median arcuate ligament (MAL) syndrome is an uncommon condition caused by the external compression of the celiac trunk by the median arcuate ligament. In the current era of technological advancement, this syndrome may be corrected through the laparoscopic approach. We report two patients who were diagnosed as MAL syndrome and underwent laparoscopic division of MAL fibers at our institute. Both the patients improved symptomatically following the procedure and were discharged on the fourth post-operative day. Also, they remained symptom free during subsequent follow-up period of 1 year and 8 months, respectively. Laparoscopic approach to correct the MAL syndrome is feasible and safe. It may be the preferred modality of treatment in view of its superior visualization and lack of morbidity. However, adequate experience in advanced laparoscopic surgery is required before attempting this procedure.

Long-term results of hepatic hydatid disease managed using palanivelu hydatid system: Indian experience in tertiary center.

BACKGROUND: Incidence of hepatic hydatid disease is increasing due to globalization. Surgery is the gold standard treatment. Laparoscopy has gained enough evidence regarding its safety and efficacy. Complete evacuation of hydatid contents without spillage remains a challenge. We aimed to determine long-term results of hepatic hydatid disease managed laparoscopically using palanivelu hydatid system (PHS) at our institution. METHODS: One hundred and five patients underwent laparoscopic surgical management using the PHS at our institute from May 1997 to May 2013. Clinical presentations, surgical strategy, postoperative morbidity, and long-term recurrence rate were evaluated. RESULTS: Of the 105 patients, 76 were male and 29 female with a mean age of 32 years (range 14-71 years). The most common presentation was abdominal pain in 61 patients (58%). Sixteen patients had multiple cysts of which nine had involvement of both lobes. Seventy-seven (73.3%) cysts were uncomplicated. Nineteen (18.09%) had a cyst-biliary communication, two were ruptured cysts, and seven were recurrent cysts. All patients underwent successful laparoscopic management where conservative surgery was performed in 94 patients and radical surgery in 11 patients. Post-operative morbidity was seen in 18 (17.14 %) patients, which included deep cavity infection in two cases, post-operative bile leak in 13 cases, and duodenal injury in one case without any mortality. Mean long-term follow-up was 36 months (range 6 months-5 years) with recurrence in two cases. CONCLUSION: Our long-term results with PHS showed good outcomes in the laparoscopic management of hepatic hydatid disease with conservative surgery as the preferred approach reserving radical surgery only in selected cases.

Whole-genome shotgun sequencing of the sulfur-oxidizing chemoautotroph Tetrathiobacter kashmirensis.

The chemolithoautotrophic betaproteobacterium Tetrathiobacter kashmirensis belongs to the family Alcaligenaceae and is phylogenetically closely related to pathogens such as Taylorella and Bordetella species. While a complete inorganic sulfur oxidation gene cluster, soxCDYZAXWB, is present in its genome, pathogenicity islands or genes associated with virulence, disease, cellular invasion, and/or intracellular resistance are completely absent.