Vitamin-D Toxicity And Other Non-Malignant Causes Of Hypercalcemia: A Retrospective Study At A Tertiary Care Hospital In Pakistan.

BACKGROUND: Hypercalcemia is a common clinical problem; primary hyperparathyroidism and malignancy is commonest causes of hypercalcemia. Aetiology of hypercalcemia are changing, causes that were diseases of the past like Vitamin-D toxicity and milk alkali syndrome are observed more often. Vitamin-D deficiency is an important problem and overzealous replacement of Vitamin-D has been observed, suspected to cause toxicity. METHODS: This was a retrospective review of patients admitted at the Aga Khan University Hospital from January 2008 to December 2013 with hypercalcemia. We reviewed the electronic health records for laboratory and radiological studies, and discharge summaries to establish the cause of hypercalcemia. Patients with solid tumour malignancy were excluded from the analysis. The treatment records and hospital course of patients diagnosed with Vitamin-D toxicity were also reviewed. RESULTS: Primary hyperparathyroidism was the most common cause of hypercalcemia comprising 41 (28.2 %) patients. Vitamin-D toxicity was present in 25 (17.3%) and probable Vitamin-D toxicity 11 (7.6 %) inpatients. Vitamin-D toxicity and probable Vitamin-D toxicity together comprised 36 (24.8%) cases. Other causes of hypercalcemia included multiple myeloma 18 (12.4%) patients, tuberculosis 6 (4.1%) patients, chronic kidney disease6 (4.1%) cases, sarcoidosis 4 (2.7%) and lymphoma 3 (2.0%) patients. In 29(20%) patients a cause of hypercalcemia could not be determined and were labelled as undiagnosed cases. CONCLUSIONS: Vitamin-D toxicity was the second commonest cause of hypercalcemia after primary hyperparathyroidism. Knowledge of the prevalent and emerging causes of hypercalcemia is important for prompt diagnosis and treatment..

COMPARISON OF VITAMIN D REPLACEMENT STRATEGIES WITH HIGH-DOSE INTRAMUSCULAR OR ORAL CHOLECALCIFEROL: A PROSPECTIVE INTERVENTION STUDY.

OBJECTIVE: To ascertain the frequency of correction of vitamin D deficiency (VDD) with single or multiple doses of oral (p.o.) and intramuscular (i.m.) administration of 2 high-dose preparations of vitamin D3 (VD3). METHODS: This was a prospective intervention study conducted in an ambulatory care setting. One hundred participants with VDD (25-hydroxy vitamin D [25-OHD] <20 ng/mL) were randomized to receive a dose of 600,000 or 200,000 IU of VD3 via a p.o. or i.m. route. The main outcome measure was serum 25-OHD levels at 2, 4, and 6 months after the intervention. The same dose was repeated in participants if 25-OHD remained <30 ng/mL at 2 and 4 months. RESULTS: At 2 months, VDD was corrected in 93.8% of participants in Group 1 (600,000 IU i.m.); 83.3% in Group 2 (600,000 IU p.o.), 87.5% in Group 3 (200,000 IU i.m.), and 70.6% in Group 4 (200,000 IU p.o.). The mean changes from baseline in vitamin D levels at 2 months were 29.6 ± 13.7, 19.8 ± 12.3, 18.3 ± 10.6, and 13.7 ± 7.8 ng/mL in Groups 1, 2, 3, and 4, respectively. The mean levels remained significantly higher from baseline in all groups at all time points during the 6 months of observation. The mean 25-OHD level achieved in Group 1 was significantly higher than all other groups at 6 months. CONCLUSION: Two months after the intervention, VDD was corrected in more than 70% of participants with a single dose of either 600,000 or 200,000 IU given p.o. or i.m.

Conducting a diabetes mellitus prevention trial in women with GDM in Pakistan: a feasibility study.

BACKGROUND: Women with gestational diabetes mellitus (GDM) are at a greater risk of developing type 2 diabetes mellitus (T2DM) than women without GDM. Despite this elevated risk, few trials on the prevention of T2DM among South Asian women with GDM have been reported. Therefore, this study aimed to assess the feasibility of conducting a diabetes prevention program on women with a history of GDM to inform the development of a contextually relevant definitive trial. METHODS: Using a randomized controlled trial, women with GDM (n = 180) who delivered at the study hospitals (one public and one private teaching hospital, Karachi) with fasting blood glucose levels < 120 mg/dl at 6 weeks postpartum were randomized to the intervention (n = 88) or control arms (n = 92). Women in the intervention group received individualized home-based educational sessions from trained community health workers at 0, 1, 3, 6, and 9 months. In addition, they received short text messages, prerecorded messages, and printed educational material (calendars and pamphlets) for reinforcement. The intervention was centered on equipping women with knowledge, skills, and confidence to eat a healthy diet rich in fruits, vegetables, and low-fat dairy products and perform regular physical activity based on walking and household chores to reduce weight (up to 5% of their initial body weight). Women in the control arm received standard care. The feasibility outcomes of the study included screening, recruitment, and retention rates and in-depth interviews at 6 months post-intervention to explore women's experiences with the intervention. Descriptive analysis and thematic analysis were performed. RESULTS: Of the 324 women screened during the antenatal care visits and after delivery, 255 (78.7%) were contactable 6 weeks postpartum, and 180 (70.6%) were eligible and randomized to intervention (n = 88) and control (n = 92) groups. Loss to follow-up in the intervention and control arms was 22.7% (n = 20/88) and 18.5% (n = 17/92), respectively. Women expressed satisfaction with home-based counseling and follow-up visits, text message reminders, and printed material in the form of a calendar through our qualitative interviews. CONCLUSIONS: Home-based lifestyle modification intervention augmented with text messages and printed material is feasible. However, to evaluate the intervention's effectiveness, a larger trial is warranted to assess its long-term impact on diabetes prevention. TRIAL REGISTRATION: ISRCTN, ISRCTN11387113 . Registered 5 December 2017-retrospectively registered.

Management of iron deficiency anemia during pregnancy: a midwife-led continuity of care model.

Background: Globally, 36.5% of pregnancies are affected by anemia, particularly in low-and middle-income countries, posing significant risks to maternal and perinatal health. In rural Pakistan, 44.3% of pregnant women suffer from iron deficiency, contributing to the high prevalence of anemia. Limited accessibility to antenatal care exacerbates the challenge, necessitating innovative solutions. This study assessed a midwife-led continuity of care model, utilizing intravenous (IV) iron therapy for the management of anemia in Karachi, Pakistan. Methods: We performed a retrospective analysis of data from a prospective cohort study conducted in two primary healthcare facilities, which employed a community midwife (CMW)-led continuity of care model for antenatal care, including IV iron therapy. We extracted data from February 2021 to March 2022 for women who were diagnosed with anemia based on hemoglobin (Hb) levels, categorized as mild (10.0 to 10.9 g/dL), moderate (7.0 to 9.9 g/dL), or severe (less than 7.0 g/dL). Assessment occurred at the initial antenatal care (ANC) visit to establish baseline anemia severity, and approximately 2 weeks after intravenous (IV) iron therapy administration to evaluate post-treatment changes were considered. Results: We enrolled 114 pregnant women, where the majority presented with moderate (88.6%) anemia. After IV iron treatment, 48.5% improved to normal-mild levels, while 50% remained unchanged. Severe anemia affected 10.5% at baseline; 42% shifted to moderate and 50% to normal-mild post-treatment, with one remaining unchanged (p < 0.001). Among women enrolled in the first and second trimesters, severe anemia improved to normal-mild (50%) and moderate levels (50%) (pre-treatment: n = 10, post-treatment: n = 0), and moderate anemia decreased by 48% (pre-treatment: n = 92, post-treatment: n = 47). Conclusion: Our midwife-led model of care demonstrated an improvement in iron levels among pregnant women. The model addressed the challenges of anemia prevalence in Pakistan and underscored the significance of empowering front-line healthcare providers, such as community midwives (CMWs) for managing these common conditions.

Feasibility of a peer-supported, WhatsApp-assisted, lifestyle modification intervention for weight reduction among adults in an urban slum of Karachi, Pakistan: a mixed-methods, single-group, pretest-post-test, quasi-experimental study.

OBJECTIVES: This pilot study assessed whether a peer-supported, WhatsApp-assisted lifestyle modification intervention for weight reduction is feasible to execute a definitive trial. DESIGN: A mixed-methods, single group, pretest and post-test, quasi-experimental study. SETTING: Azam Basti, an urban slum in Karachi, Pakistan. PARTICIPANTS: Fifty participants (males and females aged 20-60) with a body mass index of >23 kg/m2, along with their nominated peers from the same family. INTERVENTION: Using motivational interviewing techniques, a trained nutritionist delivered the lifestyle modification intervention to the participants and peers for 3 days after the baseline assessment and then once monthly for 1 year. The intervention was delivered in groups using WhatsApp voice calls. The education sessions mainly focused on dietary modifications, physical activity advice and peer-support assignments to achieve a 5% wt loss from the participant's initial body weight. OUTCOMES: The feasibility measures included screening, recruitment, retention and monthly interview response rates. At 1 year, in-depth interviews (IDIs) with participants and peers were conducted to explore the facilitators, barriers, acceptability and experiences of the intervention. Changes in weight, calorie intake/day and calorie expenditure/day were also assessed. RESULTS: The recruitment and retention rates were 32% (n=50/156) and 78% (n=39/50), respectively, while the response rate for monthly interviews ranged between 66% (n=33) and 94% (n=47). The mean weight loss at 1 year was 2.2 kg, and the reduction in mean calorie intake was 386 kcal/day. There were no changes in the mean calorie expenditure. During the IDIs, participants and peers reported intervention via WhatsApp and peer support as convenient, flexible and supportive. CONCLUSIONS: The quantitative and qualitative findings of the current pilot study support the scale-up of this work with minor modifications to the screening method as well as close monitoring and motivational interviewing to improve adherence in terms of physical activity. TRIAL REGISTRATION NUMBER: NCT05928338.

Neurodevelopment assessment of small for gestational age children in a community-based cohort from Pakistan.

BACKGROUND: Children born small for gestational age (SGA) may experience more long-term neurodevelopmental issues than those born appropriate for gestational age (AGA). This study aimed to assess differences in the neurodevelopment of children born SGA or AGA within a periurban community in Pakistan. METHODS: This was a prospective cohort study in which study participants were followed from the pilot Doppler cohort study conducted in 2018. This pilot study aimed to develop a pregnancy risk stratification model using machine learning on fetal Dopplers. This project identified 119 newborns who were born SGA (2.4±0.4 kg) based on International Fetal and Newborn Growth Consortium standards. We assessed 180 children (90 SGA and 90 AGA) between 2 and 4 years of age (76% of follow-up rate) using the Malawi Developmental Assessment Tool (MDAT). FINDINGS: Multivariable linear regression analysis comparing the absolute scores of MDAT showed significantly lower fine motor scores (ß: -0.98; 95% CI -1.90 to -0.06) among SGAs, whereas comparing the z-scores using multivariable logistic regression, SGA children had three times higher odds of overall z-scores ≤-2 (OR: 3.78; 95% CI 1.20 to 11.89) as compared with AGA children. INTERPRETATION: SGA exposure is associated with poor performance on overall MDAT, mainly due to changes in the fine motor domain in young children. The scores on the other domains (gross motor, language and social) were also lower among SGAs; however, none of these reached statistical significance. There is a need to design follow-up studies to assess the impact of SGA on child's neurodevelopmental trajectory and school performance.

Cohort profile: the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) - Pakistan.

PURPOSE: Pakistan has disproportionately high maternal and neonatal morbidity and mortality. There is a lack of detailed, population-representative data to provide evidence for risk factors, morbidities and mortality among pregnant women and their newborns. The Pregnancy Risk, Infant Surveillance and Measurement Alliance (PRISMA) is a multicountry open cohort that aims to collect high-dimensional, standardised data across five South Asian and African countries for estimating risk and developing innovative strategies to optimise pregnancy outcomes for mothers and their newborns. This study presents the baseline maternal and neonatal characteristics of the Pakistan site occurring prior to the launch of a multisite, harmonised protocol. PARTICIPANTS: PRISMA Pakistan study is being conducted at two periurban field sites in Karachi, Pakistan. These sites have primary healthcare clinics where pregnant women and their newborns are followed during the antenatal, intrapartum and postnatal periods up to 1 year after delivery. All encounters are captured electronically through a custom-built Android application. A total of 3731 pregnant women with a mean age of 26.6±5.8 years at the time of pregnancy with neonatal outcomes between January 2021 and August 2022 serve as a baseline for the PRISMA Pakistan study. FINDINGS TO DATE: In this cohort, live births accounted for the majority of pregnancy outcomes (92%, n=3478), followed by miscarriages/abortions (5.5%, n=205) and stillbirths (2.6%, n=98). Twenty-two per cent of women (n=786) delivered at home. One out of every four neonates was low birth weight (<2500 g), and one out of every five was preterm (gestational age <37 weeks). The maternal mortality rate was 172/100 000 pregnancies, the neonatal mortality rate was 52/1000 live births and the stillbirth rate was 27/1000 births. The three most common causes of neonatal deaths obtained through verbal autopsy were perinatal asphyxia (39.6%), preterm births (19.8%) and infections (12.6%). FUTURE PLANS: The PRISMA cohort will provide data-driven insights to prioritise and design interventions to improve maternal and neonatal outcomes in low-resource regions. TRIAL REGISTRATION NUMBER: NCT05904145.

Lifestyle changes and glycemic control in type 1 diabetes mellitus: a trial protocol with factorial design approach.

BACKGROUND: Type 1 diabetes (T1D) has been increasing globally over the past three decades. Self-monitoring of blood glucose is a challenge in both developed as well as developing countries. Self-management guidelines include maintaining logbooks for blood glucose, physical activity, and dietary intake that affect glycated hemoglobin (HbA1c) and a multitude of life-threatening acute complications. Innovative, cost-effective interventions along with beneficial lifestyle modifications can improve home-based self-monitoring of blood glucose in T1D patients. The overall objective of this study is to evaluate the relationship between maintaining log books for blood glucose levels, reinforcement by e-messages, and/or daily step count and changes in HbA1c. METHODS/DESIGN: A randomized controlled trial will enroll participants aged 15 years and above in four groups. Each group of 30 participants will be working with a newly designed standard log book for documenting their blood glucose. The first group will be entirely on routine clinical care, the second group will be on routine care and will receive an additional e-device for recording step count (fit bit), the third group will receive routine care and daily motivational e-messages to maintain the log book, and the fourth group along with routine care will receive an e-device for measuring step count (fit bit) and e-messages about maintaining the log book. Patients will be enrolled from pediatric and endocrine clinics of a tertiary care hospital in Karachi. All groups will be followed up for a period of 6 months to evaluate outcomes. Log book data will be obtained every 3 months electronically or during a patient's clinic visit. HbA1c as a main outcome will be measured at baseline and will be evaluated twice every 3 months. A baseline questionnaire will determine the socio-demographic, nutritional, and physical activity profile of patients. Clinical information for T1D and other co-morbidities for age of onset, duration, complications, hospitalizations, habits for managing T1D, and other lifestyle characteristics will be ascertained. Behavioral modifications for maintaining daily log books as a routine, following e-messages alone, fit bit alone, or e-messages plus using fit bit will be assessed for changes in HbA1c using a generalized estimated equation. DISCUSSION: The proposed interventions will help identify whether maintaining log books for blood glucose, motivational e-messages, and/or daily step count will reduce HbA1c levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03864991. March 6, 2019.