Prevalence of undiagnosed metabolic syndrome using three different definitions and identifying associated risk factors among apparently healthy adults in Karachi, Pakistan: a cross-sectional survey in the year 2022.

OBJECTIVE: To determine the prevalence and associated risk factors of undiagnosed metabolic syndrome (MetS) using three different definitions among apparently healthy adults of Karachi, Pakistan. METHODS: This community-based cross-sectional survey was conducted in Karachi, Pakistan, from January 2022 to August 2022. A total of 1065 healthy individuals aged 25-80 years of any gender were consecutively included. MetS was assessed using the National Cholesterol Education Program for Adult Treatment Panel (NCEP-ATP) III guidelines, International Diabetes Federation (IDF), and modified NCEP-ATP III. RESULTS: The prevalence of MetS was highest with the modified NCEP-ATP III definition at 33.9% (95% CI: 31-36), followed by the IDF definition at 32.2% (95% CI: 29-35). In contrast, the prevalence was lower at 22.4% (95% CI: 19-25) when using the NCEP ATP III definition. The risk of MetS significantly increases with higher BMI, as defined by the IDF criteria (adjusted OR [ORadj] 1.13, 95% CI 1.09-2.43), NCEP-ATP III criteria (ORadj 1.15, 95% CI 1.11-1.19), and modified NCEP-ATP III criteria (ORadj 1.16, 95% CI 1.12-1.20). Current smokers had significantly higher odds of MetS according to the IDF (ORadj 2.72, 95% CI 1.84-4.03), NCEP-ATP III (ORadj 3.93, 95% CI 2.55-6.06), and modified NCEP-ATP III (ORadj 0.62, 95% CI 0.43-0.88). Areca nut use was associated with higher odds of MetS according to both IDF (ORadj 1.71, 95% CI 1.19-2.47) and modified NCEP-ATP III criteria (ORadj 1.58, 95% CI 1.10-2.72). Furthermore, low physical activity had significantly higher odds of MetS according to the NCEP-ATP III (ORadj 1.36, 95% CI 1.01-1.84) and modified NCEP-ATP III criteria (ORadj 1.56, 95% CI 1.08-2.26). CONCLUSION: One-third of the healthy individuals were diagnosed with MetS based on IDF, NCEP-ATP III, and modified NCEP-ATP III criteria. A higher BMI, current smoking, areca nut use, and low physical activity were significant factors.

Impact of Treviamet® & Treviamet XR® on quality of life besides glycemic control in type 2 DM patients.

BACKGROUND: Maintaining the quality of life is the main objective of managing type 2 diabetes (T2DM) (QoL). Since it is a key factor in patient motivation and adherence, treatment-related QoL has always been considered when choosing glucose-lowering medicines. The objective of the study was to evaluate the quality of life besides glycemic control among type 2 diabetes mellitus patients receiving Treviamet® & Treviamet XR® (Sitagliptin with Metformin) in routine care. METHODS: It was a prospective, open-label, non-randomized clinical trial including T2DM patients uncontrolled on Metformin therapy. All patients received Treviamet® & Treviamet XR® for six months. Sequential changes in QoL, fasting plasma glucose, HbA1c, body weight, and blood pressure were monitored from baseline to 3 consecutive follow-up visits. The frequency of adverse events (AEs) was also noted throughout the study. RESULTS: A total of 504 patients were screened; 188 completed all three follow-ups. The mean QoL score significantly declined from 57.09% at baseline to 33.64% at the 3rd follow-up visit (p < 0.01). Moreover, a significant decline in mean HbA1c and FPG levels was observed from baseline to 3rd follow-up visit (p < 0.01). Minor adverse events were observed, including abdominal discomfort, nausea, flatulence, and indigestion. Gender, HbA1c, diarrhea, and abdominal discomfort were significant predictors of a patient's QoL, as revealed by the Linear Regression Model (R2 = 0.265, F(16, 99) = 2.231). CONCLUSION: Treviamet® & Treviamet XR® significantly improved glycemic control (HbA1c levels) and QoL in T2DM patients without serious adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT05167513), Date of registration: December 22, 2021.

Role of anthropometric indices as a screening tool for predicting metabolic syndrome among apparently healthy individuals of Karachi, Pakistan.

Introduction: Anthropometric indices are affordable and non-invasive methods for screening metabolic syndrome (MetS). However, determining the most effective index for screening can be challenging. Objective: To investigate the accuracy of anthropometric indices as a screening tool for predicting MetS among apparently healthy individuals in Karachi, Pakistan. Methods: A community-based cross-sectional survey was conducted in Karachi, Pakistan, from February 2022 to August 2022. A total of 1,065 apparently healthy individuals aged 25 years and above were included. MetS was diagnosed using International Diabetes Federation guidelines. Anthropometric indices were defined based on body mass index (BMI), neck circumference (NC), mid-upper arm circumference (MUAC), waist circumference (WC), waist to height ratio (WHtR), conicity index, reciprocal ponderal index (RPI), body shape index (BSI), and visceral adiposity index (VAI). The analysis involved the utilization of Pearson's correlation test and independent t-test to examine inferential statistics. The receiver operating characteristic (ROC) analysis was also applied to evaluate the predictive capacities of various anthropometric indices regarding metabolic risk factors. Moreover, the area under the curve (AUC) was computed, and the chosen anthropometric indices' optimal cutoff values were determined. Results: All anthropometric indices, except for RPI in males and BSI in females, were significantly higher in MetS than those without MetS. VAI [AUC 0.820 (95% CI 0.78-0.86)], WC [AUC 0.751 (95% CI 0.72-0.79)], WHtR [AUC 0.732 (95% CI 0.69-0.77)], and BMI [AUC 0.708 (95% CI 0.66-0.75)] had significantly higher AUC for predicting MetS in males, whereas VAI [AUC 0.693 (95% CI 0.64-0.75)], WHtR [AUC 0.649 (95% CI 0.59-0.70)], WC [AUC 0.646 (95% CI 0.59-0.61)], BMI [AUC 0.641 (95% CI 0.59-0.69)], and MUAC [AUC 0.626 (95% CI 0.57-0.68)] had significantly higher AUC for predicting MetS in females. The AUC of NC for males was 0.656 (95% CI 0.61-0.70), while that for females was 0.580 (95% CI 0.52-0.64). The optimal cutoff points for all anthropometric indices exhibited a high degree of sensitivity and specificity in predicting the onset of MetS. Conclusion: BMI, WC, WHtR, and VAI were the most important anthropometric predictors for MetS in apparently healthy individuals of Pakistan, while BSI was found to be the weakest indicator.

Risk Assessment for Cardiovascular Disease Using the Framingham Risk Score and Globorisk Score Among Newly Diagnosed Metabolic Syndrome Patients.

Purpose: The presence of metabolic syndrome (MetS) is linked to an increased risk of cardiovascular disease (CVD) development. In this study, CVD risk was calculated among individuals with newly diagnosed MetS using the Framingham Risk Score (FRS) and Globorisk Score. The FRS and Globorisk score are particularly relevant in predicting CVD risk as these scores include key MetS-related risk factors like blood pressure, cholesterol levels, and age. Patients and Methods: A community-based cross-sectional study was conducted at various sites in Karachi, Pakistan, from February 2022 to August 2022. Newly diagnosed cases of MetS with no physical disability, known illness, and not taking any regular medication were recruited. MetS was defined based on the definition of International Diabetes Federation. The major outcome was 10-year risk for CVD using the FRS and Globorisk Score. Results: Of 304 patients, 59.2% were classified as low risk according to FRS, while 20.4% were classified as moderate and high risk each. Using the Globorisk score, 44.6% of 224 patients were classified as low risk, 34.4% as moderate risk, and 21.0% as high risk. A moderate positive correlation was observed between the two CVD risk scores (r = 0.651, 95% CI 0.58-0.71). Both risk scores have reported age, gender, and current smokers as significant risk factors in predicting CVD in 10-years (P < 0.05). Conclusion: The outcome of both CVD risk scores predicted moderate-to-high risk of CVD in 10-years in almost half of the newly diagnosed patients with MetS. In particular, the risk of development of CVD in 10-years in newly diagnosed MetS is higher with increasing age, in male gender, and current smokers.

Comparison of empagliflozin and vildagliptin for efficacy and safety in type 2 diabetes mellitus in the Pakistani population.

Background: Diabetes mellitus (DM) is a chronic disease that needs early management to prevent complications and premature mortality. Therefore, it is essential to select evidence-based drugs available to control diabetes and limit the progression to related complications. This study aimed to compare the efficacy and safety of empagliflozin and vildagliptin in people with type 2 DM. Methods: This was an open-label, parallel randomized controlled trial (NCT05359432) conducted at two tertiary care hospitals in Karachi, Pakistan. After obtaining consent, participants were randomized into two groups. The first group was given empagliflozin (10 mg once or two times daily) with metformin, and the second group got vildagliptin (50 mg once or two times daily) with metformin. HbA1c, high-density lipoprotein (HDL) levels, systolic blood pressure, fasting blood glucose, and body weight were measured at the baseline and 24-week visits. Results: A total of 120 patients fulfilled the selection criteria and then underwent randomization to be placed into empagliflozin and vildagliptin groups. The mean change in HbA1c (-0.97% ± 0.68 for empagliflozin and -0.82% ± 1.57 for vildagliptin) was statistically similar in both groups (p-value = 0.980). No statistically significant difference was observed between the two groups for safety parameters such as eGFR (p = 0.46), serum ALT (p = 0.13), LDL (p = 0.23), total cholesterol (p = 0.49), and triglycerides (p = 0.49). Conclusion: Results of the study highlight that vildagliptin and empagliflozin have a significant beneficial effect in reducing HbA1c, fasting blood glucose, systolic blood pressure, and weight of participants. Both drugs had no differences when compared on safety parameters.

Filicide In Depressive Psychosis: Case Report Of An Emotionally Unstable Woman Slaughtering Her Two Children.

Filicide is the murder of a child by the parent. It is associated with various psychiatric and nonpsychiatric conditions. We herein present a case report of a filicide by an emotionally unstable mother suffering from depressive psychosis. A thirty years old woman previously treated for depression with psychotic features, having undergone electro-convulsive therapy and on oral medication three years ago was brought by the police for psychiatric assessment. She had slaughtered her two sons of 4 and 7 years of age three days ago without any guilt or remorse. She had low mood, irritability, crying spells, hopelessness and loss of sleep, appetite and sexual desires for the past six months along with the delusions of poverty and infidelity for the past two months. She was a chain smoker. Multiple deliberate self-harm and suicidal attempts were reported in the past two months. She had disturbed family life and multiple conflicts with the husband. Psychometrics revealed BDI score of 32, BPRS score of 39 and PCL-R score of 28. She was diagnosed as a case of depressive psychosis with emotionally unstable personality traits leading to impaired judgment and poor comprehension of the consequences of her actions. This case report highlights the importance of accurately and timely diagnosing and managing a mental health disorder in order to avoid the harm towards self and others.

Boosting NAD+ with a small molecule that activates NAMPT.

Pharmacological strategies that boost intracellular NAD+ are highly coveted for their therapeutic potential. One approach is activation of nicotinamide phosphoribosyltransferase (NAMPT) to increase production of nicotinamide mononucleotide (NMN), the predominant NAD+ precursor in mammalian cells. A high-throughput screen for NAMPT activators and hit-to-lead campaign yielded SBI-797812, a compound that is structurally similar to active-site directed NAMPT inhibitors and blocks binding of these inhibitors to NAMPT. SBI-797812 shifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT at His247, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD+. These effects of SBI-797812 turn NAMPT into a "super catalyst" that more efficiently generates NMN. Treatment of cultured cells with SBI-797812 increases intracellular NMN and NAD+. Dosing of mice with SBI-797812 elevates liver NAD+. Small molecule NAMPT activators such as SBI-797812 are a pioneering approach to raise intracellular NAD+ and realize its associated salutary effects.

Pregnancy complicated by systemic lupus erythematosus and its outcome over 10 years.

The aim was to study the feto-maternal outcome of pregnancies complicated by systemic lupus erythematosus (SLE). Analysis of a prospectively-maintained database of 73 patients (June 2006-March 2016) was done. Diagnosis of SLE was made by ACR(American College of Rheumatology)-criteria. Protocol scans and blood tests were done and patients with active disease were followed biweekly for 28 weeks, and weekly thereafter. Mean age + SD was 29 ± 4.9. SLE was diagnosed before conception in 86% of patients. A total of 33% had active disease status during pregnancy and out of them 58% had a flare of SLE, compared to 26% who were in remission (p = .008). SLE activity had no effect on the rate of foetal demise (p = .57). Overall pregnancy loss was 14% with no maternal mortality. The incidence of SLE flare during pregnancy was significantly higher in patients who had active disease. But the incidence of foetal demise was not affected by disease activity. Impact Statement What is already known on this subject: SLE is one of the most common immunological disorders associated with pregnancy. Both SLE and pregnancy tend to influence each other due to complex interaction. The opinion seems to be divided regarding influence of pregnancy on SLE flare in world literature. What the results of this study add: Our data suggests a significantly greater incidence of SLE flare during pregnancy in patients with active disease, than in those in remission. What the implications are of these findings for clinical practice and/or further research: Though the majority of these flares were not major and did not require hospitalisation, these patients usually have a bad obstetric history. However, with multidisciplinary involvement, SLE activity in our series was not an independent predictor of a poor pregnancy outcome.

Multiplexed approaches correlating mitochondrial health to cell health using microcapillary cytometry.

Mitochondria are critical cellular organelles that play a fundamental role in cellular metabolism and oxidative stress and are well known to trigger multiple cell death pathways. The study of sequence of mitochondrial events as it relates to apoptotic/cell death events can provide critical insights into mechanism of cellular homeostasis, stress and death. Availability of rapid and simplified cytometric testing methods for evaluating mitochondrial changes, apoptosis and cell death in parallel can greatly enhance our understanding of mechanism of compound action. In this study, we investigated a series of compounds to evaluate apoptotic/cell death effects in context of mitochondrial changes using plate-based assays on Guava® easyCyte systems. Studies utilized multiplexed assays for mitochondrial membrane potential changes and apoptosis/cell death markers and allowed for easy identification of hit compounds. Dose and time response studies with Niclosamide, an anti-helmintic drug and comparison of effects with Gambogic acid and celastrol demonstrated early and significant mitochondrial impacts for niclosamide and gambogic acid. No apoptotic or cell death impacts were observed in parallel at low doses/short times of incubation for niclosamide, while increased time with niclosamide caused increase in mitochondrial, apoptotic and cell death response. The method demonstrates great power in being able to distinguish between potency of compounds and conditions in modulating mitochondrial/apoptotic changes. The simplicity of the assays described coupled with the ease of use of plate based microcapillary cytometry can provide researchers valuable tools to obtain a more comprehensive insight into how compounds modulate mitochondria and its relationship with subsequent apoptosis/cell death pathways.

BRIGHT Guidelines on Self-Monitoring of Blood Glucose.

Pakistan, a developing country with limited resources, is having huge burden of diabetes and its complications. The local health care providers face limitations due to the related cost while emphasizing on self monitoring of blood glucose. The lack of health care infrastructure, non-affordability of the patients and non-existence of national guidelines are the most significant obstacles. Having realized these issues we decided to initiate a project of self monitoring of blood glucose, "BRIGHT (Better Recommendations, Implementation and Guideline development for Health care providers and their Training). After extensive literature search, the project team, approached and communicated with "Advisory Board for the Care of Diabetes (ABCD) of Pakistan" for their expert opinion and suggestions. The board members belong to the faculty of main teaching hospitals of the four provinces of Pakistan thus ensuring national representation. The endorsement of these guidelines has paved the way for their uniform implementation all over the country. Development of these Guidelines is the first part of BRIGHT project. In the next phase, we have started training of health care providers. Five mega programs have been conducted in this regard in the major cities. So far a patient's log book has also been designed and distributed. Like all other guidelines, this is a living document which will be revised and updated from time to time in the light of new information which becomes available.

Drainage vs no drainage in secondary peritonitis with sepsis following complicated appendicitis in adults in the modern era of antibiotics.

AIM: To compare the profile of postoperative outcome in secondary peritonitis with sepsis due to complicated appendicitis in two cohorts (drainage vs no-drainage) after appendicectomy in adults in the modern era of effective antibiotics. METHODS: A retrospective review of all adult patients who were operated for secondary peritonitis with sepsis due to complicated appendicitis was carried out. Total of 209 patients were identified from May 2005 to April 2009 with operative findings of gangrenous or perforated appendix. The patients were divided into two cohorts, those where prophylactic drainage was established (n = 88) and those where no drain was used (n = 121). Abdominal drain was removed once the drainage ceased or decreased (< 10-20 mL/d in closed system of drainage or when once daily dressing was minimally soaked in open system). Broad spectrum antibiotics to cover the gut flora were started in both cohorts at diagnosis and were stopped once septic features resolved. Peritoneal fluid for aerobic culture and sensitivity were routinely obtained intra operatively; however antibiotic regimens were not changed unless patient failed to respond to the antibiotics based on the institutional protocol. The co-morbidities and their influence on primary end points were noted. Immunocompromised patients, appendicitis complicated by inflammatory bowel disorder and tumors were excluded from the study. RESULTS: Disease stratification and other demographic features were comparable in both cohorts. There was zero mortality in drainage group while as one patient (0.82%) died in the non-drainage group. The median duration (in days) of hospital stay (6.5 vs 4); antibiotic use (5 vs 3.5); regular parental analgesic use (5 vs 3.5) and paralytic ileus (2.5 vs 2) was more common in the drainage group. Incidence of major wound infection in patients 14 (15.9%) vs 22 (18.18%) and residual intra-abdominal sepsis (inter loop collection/abscess) -7 (8%) vs 13 (10.74%) requiring secondary intervention was not significantly different in drainage and non-drainage cohorts respectively. One patient in the drainage cohort had faecal fistula (1.1%). CONCLUSION: The complicated appendicitis in the modern era of antibiotics does not necessitate the use of prophylactic drain placement which at times may even prove counterproductive.

Simplified evaluation of apoptosis using the Muse cell analyzer.

The degree of apoptosis in a cell population is an important parameter of cell health and is characterized by distinct morphological changes. Current methods of accurate detection and measurement of cellular apoptosis require expensive and complicated instrument platforms and expertise. The Muse Cell Analyzer is a unique instrument that enables multidimensional cell health analysis on a single platform. In this study, we used the Muse Cell Analyzer for apoptosis studies using the Muse Annexin V & Dead Cell Assay. The assay is based on the detection of phosphatidylserine (PS) on the surface of apoptotic cells. The results obtained from Muse Cell Analyzer were compared with traditional methods for apoptosis analysis. Our results indicate that Muse Annexin V & Dead Cell Assay and software module enabled the acquisition of accurate and highly precise measurements of cellular apoptosis. The assay is versatile and works with both suspension and adherent cell lines and multiple treatment conditions.

Jejunogastric intussusception presenting as tumor bleed.

Jejunogastric intussusception (JGI) is a rare but serious complication of previous gastrectomy or gastrojejunostomy, and a delayed diagnosis can lead to catastrophe. It can present as hematemesis, and an endoscopist aware of the condition can diagnose it early. We present a case of JGI presenting as hematemesis and diagnosed as tumor bleed on endoscopy. Diagnosis of JGI was confirmed on laparotomy, gangrenous efferent limb was resected and a fresh gastrojejunostomy performed.

Subcutaneous internal lateral sphincterotomy (SILS) versus nitroglycerine ointment in anal fissure: a prospective study.

AIM: To compare the results of subcutaneous internal lateral sphincterotomy under local anesthesia and nitroglycerin ointment treatments in acute and chronic anal fissures. METHODS: This was a comparative, prospective study of 340 patients of acute and chronic anal fissure. The patients voluntarily opted either for the surgical procedure under local anesthesia, or the nitroglycerin treatment. All the patients were followed with regular checkups and complaints were documented. RESULTS: Except for 1.75% patients having bleeding/hematoma formation, and with a dropout of 2.60% patients, no failure, recurrence or long term complications like incontinence, were observed in patients who underwent subcutaneous internal lateral sphincterotomy after a mean follow up of 28 months. With surgical treatment pain, bleeding per rectum and constipation showed significant improvement as compared to nitroglycerin treatment. Fissure healing was 100% in surgical group as compared to 56.90% in medical group (P=0.000, odds ratio=344.6). Nitroglycerin was equally effective in acute and chronic fissures (P=0.096). CONCLUSION: Subcutaneous internal lateral sphincterotomy under local anesthesia is more curative, easy and safe, in the hands of a beginner as well as an experienced surgeon, with highest patient satisfaction, and should be considered as the first line of therapy in both chronic and resistant/recurrent acute anal fissures.