A Hybrid Test Optimization Framework - Coupling Genetic Algorithm with Local Search Technique

Quality of test cases is determined by their ability to uncover as many errors as possible in the software code. In our approach, we applied Hybrid Genetic Algorithm (HGA) for improving the quality of test cases. This improvement can be achieved by analyzing both mutation score and path coverage of each test case. Our approach selects effective test cases that have higher mutation score and path coverage from a near infinite number of test cases. Hence, the final test set size is reduced which in turn reduces the total time needed in testing activity. In our proposed framework, we included two improvement heuristics, namely RemoveTop and LocalBest, to achieve near global optimal solution. Finally, we compared the efficiency of the test cases generated by our approach against the existing test case optimization approaches such as Simple Genetic Algorithm (SGA) and Bacteriologic Algorithm (BA) and concluded that our approach generates better quality test cases

Usage of Glimepiride/Metformin Fixed-dose Combination in Young Individuals with Type 2 Diabetes: The Indian Experience

Background: The prevalence of diabetes has been rising among the younger population and is a cause for concern. The present case-based questionnaire survey evaluated the treatment pattern and clinical experience of healthcare professionals (HCPs) in prescribing glimepiride/metformin fixed-dose combination (FDC) to young diabetes patients (up to 40 years of age) in the Indian setting. Material and methods: A retrospective, multicenter, observational, questionnaire-based survey was conducted in Indian healthcare centers using medical records of patients having type 2 diabetes mellitus (T2DM), who were prescribed different strengths of glimepiride/metformin FDCs. Data was collected from the patients’ medical records and were analyzed using statistical tests. Results: A total of 2,715 patients aged between 18 and 40 years were included in the study. Mean diabetes duration among the young patients was 2.76 ± 1.97 years. Among the young T2DM patients, 83.2% patients received glimepiride/metformin FDC as first-line therapy, and 16.8% received it as second-line therapy. Hypoglycemia at 6 months was noted in only 2.47% of the young patients. Mean glycated hemoglobin (HbA1c) before and after treatment was 8.7% ± 3.4% and 7.3% ± 3.9%, respectively. Mean fasting plasma glucose (FPG) was 171.8 ± 80.1 mg/dL in patients prior to treatment initiation and came down to 122.8 ± 41.8 mg/dL after treatment with glimepiride/metformin FDC. Mean postprandial plasma glucose (PPG) prior to combination therapy use was 248.7 ± 64.0 mg/dL and dropped to 177.2 ± 39.9 mg/dL after treatment. Good to excellent efficacy and tolerability were reported for 86% and 86.6% patients, respectively. Conclusion: This case-based questionnaire survey demonstrates the usage pattern of various strengths of glimepiride/metformin FDCs and the HCPs’ practice approach regarding the use of this combination in young T2DM patients in the Indian setting. The combination is commonly prescribed to young diabetes patients in India and is associated with beneficial effects on glycemic parameters

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia.

BACKGROUND: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. METHODS/DESIGN: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. DISCUSSION: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01212328

Efficacy and tolerability of GLP-1 agonists in patients with type 2 diabetes mellitus: an Indian perspective

Glucagon like peptide-1 (GLP-1) agonists have been able to address the unmet needs of type 2 diabetes patients across the world. Indian patients with type 2 diabetes have also been able to benefit from effects of GLP-1 analogues to a more or less similar extent compared with patients from other parts of the world. As there is no nationwide data on use of GLP-1 agonists in India, we used the clinical data from different studies and compared them with the global data on GLP-1 analogues. The review is limited to only two approved GLP-1 analogues in India: exenatide and liraglutide. The efficacy of GLP-1 analogues, in terms of glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and postprandial glucose (PPG), is found to be similar in Indian patients compared with the global data. The other beneficial effects such as weight loss, incidence of hypoglycaemia were found to be on similar lines in the Indian setting. In a single-centre study, liraglutide reduced the dose of antihypertensive medications due to its effect on blood pressure. The gastrointestinal adverse effects such as nausea and vomiting were major adverse events, but these were transient and varied from one particular agent to another. Liraglutide is found to be superior in terms of compliance compared with exenatide in the Indian setting. Overall, the GLP-1 analogues have presented a treatment option that gives patient a benefit of glycaemic control, weight loss and very low incidence of hypoglycaemia, but the cost of the therapy presents a major barrier

Association between glycemic gap and adverse outcomes in Critically Ill patients with diabetes

Objectives: Glycemic excursions are commonly seen in patients admitted to the Intensive Care Unit (ICU) and are related to adverse outcomes. Glycemic gap is a marker of this excursion in patients with diabetes. It can be used to predict adverse outcomes in patients with diabetes admitted to the ICU. It is calculated by subtracting A1C-derived average glucose (ADAG) = ([28.7 × HbA1c]-46.7) from plasma glucose at admission. Objective of this study was to correlate glycemic gap and adverse outcomes in patients with type 2 diabetes mellitus (DM) admitted to the ICU. Materials and Methods: We conducted an ambispective study to include patients with type 2 DM admitted to the ICUs from July 2015 to June 2016. The following adverse outcomes were recorded: Multiorgan dysfunction syndrome (MODS), acute respiratory distress syndrome (ARDS), shock, upper gastrointestinal (UGI) bleed, acute kidney injury (AKI), and acute respiratory failure (ARF). Results: A total of 200 patients were enrolled, with a mean age ± standard deviation of 62 ± 11.24 years, and 64.5% were males. The median (interquartile range) duration of hospital stay and ICU stay were 8 (6–12) days and 4 (3–7) days, respectively. The most common primary diagnosis was cardiovascular (39.5%) followed by neurological (16.5%), infection at diagnosis (16.5%), respiratory (14%), gastrointestinal (7.5%), and others (6%). A higher glycemic gap was associated with occurrence of MODS (P < 0.01), ARDS (P = 0.026), shock (P = 0.043), UGI bleed (P = 0.013), AKI (P = 0.01), and ARF (P < 0.01). Glycemic gap cutoffs of 43.31, 45.26, and 39.12 were found to be discriminatory for predicting ICU mortality (area under the receiver operating characteristic [AUROC]=0.631, P = 0.05), MODS (AUROC = 0.725, P < 0.001), and ARF (AUROC = 0.714, P < 0.001). Conclusion: This study showed that higher glycemic gap levels were associated with an increased risk of MODS, ARDS, shock, UGI bleed, AKI, and ARF. Glycemic gap is a tool that can be used to determine prognosis in patients with diabetes admitted to the ICU

Studies - Management of premenstrual acne with Cox-2 inhibitors: A placebo controlled study

BACKGROUND: Premenstrual acne is poorly understood, the accepted hypothesis is 30 years old. AIMS: Here we test the hypothesis that premenstrual acne can be suppressed using Cox-2 inhibitors. METHODS: Eighty women with premenstrual acne were enrolled in a trial where they were given rofecoxib, a Cox-2 inhibitor or placebo for 10 days for two cycles and were evaluated using acne severity index and inflammatory acne counts. RESULTS: Rofecoxib was more effective than the placebo. CONCLUSIONS: Although the number studied is small, the results suggest that rofecoxib is effective in the management of premenstrual acne and that prostaglandin PGE2 may be involved in its pathogenesis

Study - Management of premenstrual acne with Cox-2 inhibitors: A placebo controlled study

BACKGROUND: Premenstrual acne is poorly understood, the accepted hypothesis is 30 years old. AIMS: Here we test the hypothesis that premenstrual acne can be suppressed using Cox-2 inhibitors. METHODS: Eighty women with premenstrual acne were enrolled in a trial where they were given rofecoxib, a Cox-2 inhibitor or placebo for 10 days for two cycles and were evaluated using acne severity index and inflammatory acne counts. RESULTS: Rofecoxib was more effective than the placebo. CONCLUSIONS: Although the number studied is small, the results suggest that rofecoxib is effective in the management of premenstrual acne and that prostaglandin PGE2 may be involved in its pathogenesis

Study of effects of gender-affirming hormone therapy on bone mineral density in individuals with gender dysphoria

Introduction: Gender affirming hormone therapy (GAHT) is the mainstay treatment in transitioning individuals and has positive physical and psychological effects. Among the things to monitor in transgender patients on long-term hormones, bone health is an essential consideration. As the calcium intake in the Indian population is less, and many gender-incongruent individuals may not take adequate calcium in their diet, we needed data on the bone health of Indians with gender dysphoria as the information available globally may not apply to our population. Materials and Methods: The study was performed to assess bone mineral density in individuals with gender dysphoria who were on gender-affirming hormonal therapy for at least 6 months. It was a hospital-based cross-sectional study of bone mineral density measured at two sites – hip and spine in individuals with gender dysphoria on GAHT for at least six months. Results: A total of 30 individuals were included in this study. The mean age of individuals with Gender dysphoria was found to be 28.17 ± 6.15 years, and the age range was 19-42 years. Out of the 30 individuals, 14 were transgender males, and the remaining 16 were transgender females. Bone mineral density at the hip and spine in transgender males was 1.047 ± 0.124 g/cm2 and 1.065 ± 0.115 g/cm2, which was better compared to transgender females in whom the bone mineral density at hip and spine was 0.899 ± 0.873 g/cm2 and 0.854 ± 0.099 g/cm2 (P = 0.001 for hip; P = 0.000 for spine). The Z score at hip and spine were better in transgender males as compared to transgender females (P < 0.001 for hip; P < 0.001 for spine) when compared to genetic sex and at the spine (P = 0.001) when compared to affirmed sex. In this study, we observed that the transgender females who underwent orchidectomy had a lower mean Z score at spine compared to individuals who did not undergo the procedure. Conclusions: The current study results indicate that GAHT does have positive effects on bone health in transmen

Are patients with primary hypothyroidism in India receiving appropriate thyroxine replacement? An observational study

Background: A large proportion of patients worldwide under treatment for hypothyroidism with thyroxine show suboptimal Thyroid Stimulating Hormone (TSH) values. There is a paucity of Indian data on ′out-of-range′ TSH values in patients with primary hypothyroidism receiving levothyroxine treatment. Aim: To assess the percentage of primary hypothyroid patients with abnormal thyroid function despite being prescribed levothyroxine for at least 2 m. Materials and Methods: A cross-sectional, single visit, observational study in adult patients with primary hypothyroidism on treatment with levothyroxine for at least 2m was undertaken across 10 cities in India. Compliance to thyroxine therapy was assessed by interviewing the subjects and their quality of life was assessed by administering the SF-36 questionnaire. A random blood sample (5ml) was drawn from the study subjects during the same visit for assessing serum TSH levels. TSH levels were correlated with the current dose of levothyroxine. Results: A total of 1950 subjects (mean age 41.4 ± 11.17 years; female 81.2%, male 18.8%) with primary hypothyroidism were enrolled in the study. Of the 1925 subjects in whom TSH values were available, 808 (41.97%) were under-treated (TSH > 4 mIU/L) and 243 (12.62%) were over-treated (TSH < 0.4mIU/L). The mean dose of thyroxine in this study was 1.23 μg/kg/day (±0.85). Majority of subjects (90.79%) were compliant/moderately compliant to thyroxine therapy. Age and autoimmune hypothyroidism were the factors that had significant impact on serum TSH. Subjects with abnormal TSH had significantly lower scores for role limitation due to emotional problems (P = 0.0278) and due to physical health (P = 0.0763). Conclusion: This study concluded that around half (54%) of known hypothyroid subjects had out-of-range serum TSH despite being treated with levothyroxine for at least 2m. The mean daily dose of thyroxine (1.23 μg/kg ± 0.85) was less than the recommended full replacement dose

Heat transfer characteristics of Al2O3/water nanofluid in laminar flow conditions with circular ring insert

In this experimental investigation convective heat transfer, friction factor, and thermal enhancement characteristics of straight circular duct fitted with circular ring insert of constant heat flux boundary condition under fully developed laminar flow is presented. Tests have been conducted by using 0.1% volume concentration of Al2O3 nanofluid and water. Inserts of different pitch to diameter ratios of 6.25, 8.33, 12.5, and 16.67 with center core rod were used for this investigation. The circular ring insert shows a superior thermal performance than plain tube. The experimental results demonstrated that the Nusselt number, friction factor, and thermal enhancement factor increases with decrease in pitch to diameter ratio. The circular ring inserts of lower pitch to diameter ratio of 6.25 with nanofluid increases the Nusselt number by 165.38% compared to pure water and the friction factor, found to be 7.89 times higher than that of water. Empirical correlations are develope for Nusselt number and friction factor in terms of Reynolds number, volume concentration, and pitch ratio. The thermal performance factor was found to be greater than unity for all pitch to diameter ratios