Primary hyperparathyroidism: Experience from a tertiary care centre in Pakistan

Objective: To study the clinical, biochemical and radiological features and management outcomes of patients with primary hyperparathyroidism.Methods: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan and comprised data of patients with primary hyperparathyroidism from 2008 to 2017.Results: Out of 103 patients, 83(80.6%) were female. Overall mean age was 59.3±16.2 years. Musculoskeletal manifestations were seen in 60(58.3%) patients and renal manifestations in 28(27.2%). Ostieits fibrosa cystica was found in 04(3.88%) patients. Overall, Ultrasound neck and sestamibi scan localized the lesion in 66 (64.1%) and 77 (76.2%) patients respectively. Among 79 patients who underwent surgery, 67 (84.8%) patients had an adenoma, 05 (6.3%) had hyperplasia and 02(2.53%) patients had parathyroid carcinoma whereas histopathology was inconclusive in 5 (6.32%) out of the 79 surgically treated patients. Disease recurrence was seen in 13 out of 79(16.45%) patients who underwent surgery.Conclusion: Primary hyperparathyroidism is associated with significant morbidity in our population. Targeted measures like improving patient awareness, routine calcium screening, vitamin D supplementation and a high index of suspicion by the clinician may help in early diagnosis of the condition and thus reduce morbidity

Malignant and non-malignant causes of hypercalcemia: A retrospective study at a tertiary care hospital in Pakistan

Background: Hypercalcemia is a common electrolyte abnormality presenting with a variety of symptoms. The common causes are primary hyperparathyroidism and malignancy associated with hypercalcemia. However, iatrogenic hypercalcemia with the overzealous use of vitamin D has now emerged as another important cause of hypercalcemia over the past decade.Objective: This study aims to evaluate the causes of hypercalcemia, management strategies, and outcomes in patients admitted with hypercalcemia in a tertiary care hospital. Method: It is a retrospective study done at Aga Khan University Hospital (AKUH), Karachi after taking approval from the ethical review committee (ERC). Data were gathered about all patients admitted from 1st January 2008 to 31st December 2018. A total of 1142 patients were included in the study and their calcium levels were noted. Along with demographic details, data pertaining to their diagnosis and all investigations done to evaluate the causes of hypercalcemia were noted in a pre-defined questionnaire.Results: A total of 814 patients having hypercalcemia were included in the final analysis and their mean age was 60.8 ± 14.1 years. Male and female patients were 45.4% and 54.6%, respectively, and their mean hospital stay was 6.2 ± 5.8 days. The most common cause of hypercalcemia was malignant solid tumors (49.1%), followed by hematological malignancy (16.5%), hyperparathyroidism (10.9%), definite vitamin D toxicity (8%), chronic kidney disease (4.9%), chronic granulomatous diseases (4.7%), and probable vitamin D toxicity (3.5%). The oral cavity carcinoma (17.7%) was the most common solid tumor associated with hypercalcemia. Amongst hematological malignancy, multiple myeloma (14.4%) was the most common one. Out of 814 patients admitted with hypercalcemia, 601 (74%) patients recovered from hypercalcemia, while mortality was observed in 129 (16%) patients. Of those who expired, 110 (85.3%) had malignancy either solid tumor or hematological.Conclusion: Malignancy is the most common cause of hypercalcemia in admitted patients. The knowledge of hypercalcemia\u27s causes is of great importance so that targeted investigations can be done. Not only will it minimize the cost burden and shorten the hospitalization of patients; it will also help the physicians to decide the appropriate management accordingly. Moreover, vitamin D toxicity was also observed in a significant number of patients which highlights the common practice of using higher doses of vitamin D by physicians

Follicular thyroid carcinoma in a developing country: A 10-year retrospective study

Background: The most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines.Methodology: This was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019.Results: A total of 404 patients with thyroid carcinoma were sorted, of which 40 (10.1%) were FTC cases. Overall, 50% of the patients were in the age group of 41-60 years, and the female-to-male ratio was 1.5:1. The majority of patients (60%) presented with neck swelling, followed by bone and lung metastasis in 20% and compressive symptoms in another 20%. On fine needle aspiration cytology (FNAC), 50% had Bethesda category III-IV nodules while 10% had Bethesda category II. Overall, 50% had a total thyroidectomy while 50% had a lobectomy followed by a completion thyroidectomy. On histopathology, 23 (57.5%) patients had minimally invasive FTC while 17 (42.5%) had widely invasive FTC. A total of 17 (42.5%) patients had received RAI 30-100 mCi while 10 (25%) received more than 100 mCi.Conclusions: FTC can present with both local or metastatic symptoms. The atypical presentation of metastatic FTC should be considered, diagnosed, and managed early to limit mortality and morbidity. Ultrasound is the best diagnostic investigation of choice followed by FNAC. Surgery is the mainstay of treatment and should be followed by RAI in select cases. Thus, understanding the trend of FTC and proper planning and utilization of the resources will help developing countries in effectively treating the FTC

Relationship between estimated average glucose (eAG) and fasting plasma glucose in a cohort of Pakistani diabetic subjects

Introduction: Scientific literature is scarce on the utility of estimated average glucose (eAG) from Pakistan. Hence, there is a dire need to evaluate the relationship between eAG and fasting plasma glucose (FPG), in order to enhance our understanding of eAG and its usefulness. This study aims to investigate the relationship between FPG and eAG in diabetic patients calculated using HbA1C.Materials and methods: A retrospective study was conducted at the Aga Khan University, Karachi, Pakistan. The medical records of both genders in the age range of 18-60 years, presenting as outpatients at the endocrine clinic, labeled as DM, were reviewed from January 2013 to December 2019. The subjects were divided into three groups A (\u3c130 mg/Dl), B (130-179 mg/Dl), and C (\u3e180 mg/Dl) based on FPG levels. A correlation was compared using Spearman’s correlation. Box, whisker plots, and scatter plots were computed by R studio.Results: After excluding those with missing values for either serum Cr, FPG, and HbA1c and sub-optimal renal function based on estimated glomerular filtration rate (eGFR) a total of 4,673 cases were analyzed. Subgroup A showed good glycemic control, whereas subgroup C showed poor glycemic control. The difference between eAG and FPG was significant (p \u3c 0.0001). eAG values were found to be elevated than FPG values in groups A and B and almost the same in group C, whereas a moderately significant correlation with eAG and FPG in all three groups.Conclusion: The correlation between eAG and FPG varies with blood glucose control and was significantly higher in the poorly controlled diabetes group. As the association between the FPG and eAG levels varies with the extent of blood glucose control, reporting eAG with HbA1c by a simple formula, at no additional cost will prove to be beneficial for clinical care

Frequency of dysnatremia in patients admitted with COVID-19 infection and its prognostic implication

Objective: We aimed to investigate the frequency of dysnatremia among patients admitted with COVID-19 infection and its association with inpatient mortality.Methods: This retrospective longitudinal study was conducted for 12 weeks. Serum sodium levels were recorded at admission, during the hospital stay, and within 48 hours of discharge or death. Logistic regression was used to determine the predictors of mortality.Results: This study included 574 patients (69.7% men, age 55.6 ± 14.4 years). On admission, mean sodium was 135.9 ± 6.4 mEq/L; 39% had hyponatremia and 4.7% had hypernatremia. During admission, hypernatremia increased to 18.8%; maximum sodium in patients who survived was 140.6 ± 5.0 mEq/L versus 151.0 ± 9.9 mEq/L in those who died. The final sodium was 145.4 ± 9.4 mEq/L in patients who died versus 137.7 ± 3.7 mEq/L in those who survived (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.13-1.32). Other predictors of mortality included ischemic heart disease (OR: 3.65, 95% CI: 1.39-9.61), acute kidney injury (OR: 6.07, 95% CI: 2.39-15.42), invasive ventilation (OR: 28.4, 95% CI: 11.14-72.40), and length of stay (OR: 0.91, 95% CI: 0.86-0.97).Conclusion: Hypernatremia was frequently observed in patients who were critically ill and died and may be considered a predictor of mortality in COVID-19 infection

The utility of ultrasound in the preoperative localization of primary hyperparathyroidism: Insights from Pakistan

Objective: We aimed to evaluate and compare the diagnostic performance of ultrasound (US) and 99m-Tc sestamibi scintigraphy for the preoperative localization of primary hyperparathyroidism (PHPT).Methods: This retrospective study was conducted at the Aga Khan University Hospital in Karachi, Pakistan, and comprised the data of patients with PHPT who underwent parathyroidectomy from 2008 to 2017. Preoperative US and 99m-Tc sestamibi scintigraphy findings were recorded and compared to surgical and histological findings, which were taken as a reference standard.Results: The sensitivity of US in the preoperative localization of PHPT was 88.3%, positive predictive value (PPV) was 94.6%, and accuracy was 84.1%. The sensitivity of 99m-Tc sestamibi scintigraphy was 90.4%, PPV was 94.3%, and accuracy was 85.7%.Conclusion: US neck is an efficient tool for the preoperative localization of PHPT, demonstrating a comparable diagnostic yield with 99m-Tc sestamibi, and can serve as a credible first-line imaging modality in a resource-constrained healthcare setup

Effect of 5-minute movies shown via a mobile phone app on risk factors and mortality after stroke in a low- to middle-income country: Randomized controlled trial for the stroke caregiver dyad education intervention (Movies4Stroke)

Background: Pakistan is the sixth most populous nation in the world and has an estimated 4 million stroke survivors. Most survivors are taken care of by community-based caregivers, and there are no inpatient rehabilitation facilities.Objective: The objective of this study was to evaluate the effectiveness and safety of locally designed 5-min movies rolled out in order of relevance that are thematically delivered in a 3-month program to deliver poststroke education to stroke survivor and caregiver dyads returning to the community.Methods: This study was a randomized controlled, outcome assessor–blinded, parallel group, single-center superiority trial in which participants (stroke survivor-caregiver dyads) with first-ever stroke (both ischemic and hemorrhagic) incidence were randomized within 48 hours of their stroke into either the video-based education intervention group or the control group. The video-based education intervention group had health education delivered through short videos that were shown to the participants and their caregivers at the time of admission, before discharge, and the first and third months of follow-up after discharge. The control group had standardized care including predischarge education and counseling according to defined protocols. All participants enrolled in the video education intervention and control groups were followed for 12 months after discharge for outcome assessment in the outpatient stroke clinics. The primary outcome measures were the proportion of participants achieving control of blood pressure, blood sugar, and blood cholesterol in the video intervention versus the control group. Several predefined secondary outcomes were included in this study, of which we report the mortality and functional disability in this paper. Analysis was by performed using the intention-to-treat principle.Results: A total of 310 stroke survivors and their caregiver dyads (participant dyads) were recruited over a duration of 6 months. In total, 155 participant dyads were randomized into the intervention and control groups, each. The primary outcome of control of three major risk factors revealed that at 12 months, there was a greater percentage of participants with a systolic BP(18/54, 33% vs 11/52, 21%; P=.16), diastolic BP(44/54, 81% vs 37/52, 71%; P=.21), HbA1c levelP=.32), and low-density lipoprotein level/dL (36/51, 70% vs 30/45, 67%; P=.68) in the intervention group than in the control group. The secondary outcome reported is the mortality among the stroke survivors because the number of stroke-related complications was higher in the control group than in the intervention group (13/155, 8.4% vs 2/155, 1.3%), and this difference was statistically significant (P\u3c.001).Conclusions: The Movies4Stroke trial failed to achieve its primary specified outcome. However, secondary outcomes that directly related to survival skills of stroke survivors demonstrated the effectiveness of the video-based intervention on improving stroke-related mortality and survival without disability

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Validation of InstaDx, A clinical decision support tool information technology based application for ischemic stroke

Globally ischemic stroke is second leading cause of mortality and morbidity among adult population. Prompt diagnosis of sub-type of ischemic stroke can lead to better management and clinical outcomes. This study aims to adapt, develop and validate the InstaDx; mHealth based android application to assist ischemic stroke sub-type diagnosis for use among neurology residents against Stroke Expert (gold standard). InstaDx is an evidence- based classification algorithm for ischemic stroke, to diagnose the sub-type in the presence of multiple competing mechanisms to minimize misdiagnosis, improve prognosis and preventive management decisions. Methods: The study was conducted in three phases: adaptation and development of InstaDx, validation of InstaDx and, user uptake and feasibility of InstaDx, qualitative feedback. In the first phase, algorithms of InstaDx were created through standard guidelines and these algorithms were transferred into mHealth based android application. In the second phase a validation study was conducted at Aga Khan University Hospital, Karachi from March to August 2017. Total of 228 consecutive patients of age 2 218 years, presenting in emergency department with neurological deficits consistent with stroke were recruited and InstaDx was used for diagnosing sub-type of ischemic stroke (Large or small artery atherosclerosis or cardio-aortic embolism) by the residents. The sensitivity and specificity of InstaDx for sub-type of ischemic stroke was validated against Stroke Expert diagnosis (gold standard). In the third phase, user feedback was assessed through Focus group discussion on neurology residents to evaluate their perspectives and experiences regarding the usage of InstaDx and what further modalities can be added in the application. Results: In adaptation and development phase of InstaDx, few sequential changes were incorporated in the algorithm of ischemic stroke mechanism. According to standard guidelines, contraindications of rtPA were rectified and integrated in InstaDx. As a part of validation phase, 228 Patients with mean age 62.59 14.60 years with ischemic stroke were studied. 11.84% patients receive revascularization with tissue plasminogen activator (rtPA). The sensitivity and specificity of InstaDx for large artery arthrosclerosis was 65.91 % and 73.57 % respectively, Small artery atherosclerosis was 56.25 % and 84.18 % respectively and Cardio aortic embolism was 58.33% and 99.17 % respectively. Focus group discussion feedback identified that InstaDx was well received as an educational tool by the residents and they suggested that further advanced diagnostic capacities be built-in. Conclusion: InstaDx is a valuable sensitive and specific mHealth based application for diagnosing subtype of ischemic stroke. It provides standard algorithm to confidently assess ischemic stroke patient and focuses on important aspects of stroke care