Awareness and adherence to lifestyle modifications in hypertensive patients presenting to a tertiary care setting.

OBJECTIVE: To assess the level of awareness and adherence to lifestyle modifications in hypertensive patients. METHODS: The descriptive study was conducted from January to June 2019 at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised adult patients of either gender with hypertension history of at least 1 year. Data was collected using a structured questionnaire to evaluate the subjects' awareness and adherence to lifestyle modifications for the control of hypertension. Data was analysed using SPSS 20. RESULTS: Of the 294 patients, 160(54.4%) were women. The overall mean age was 53.3±12.1 years and mean body mass index was 27.1±5.9kg/m2, and mean duration of hypertension was 8.2±7.1 years. There were 122(41.5%) obese and 97(33%) overweight patients. Overall, 201(68.4%) patients had co-morbidities and 40(13.6%) were smokers. Of the total, 205(69.7%) knew the importance of exercise, but 104(35.4%) were doing it; 270(91.8%) were aware of restriction of sodium diet, but 244(83%) were adhering to it; 222(75.5%) knew the importance of dietary approaches to stop hypertension, but 185(62.9%) were adhering to it; and 247(84%) were aware that regular blood pressure measurement and follow-ups were important, but 150(51%) were adhering to it. CONCLUSIONS: The level of awareness regarding lifestyle modifications was found to be high in hypertensive patients, but the status of adherence was not up to the mark.

Assessment of quality of life of stroke survivors and their caregivers presenting to a tertiary care hospital in Pakistan.

OBJECTIVE: To determine the quality of life of stroke survivors and their caregivers presenting to a tertiary care setup. METHODS: The descriptive study was conducted from July to December 2019 at the Neurology Department, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised patients of either gender with ischaemic or haemorrhagic stroke aged 40-70 years and their caregivers. Data was collected using the stroke-specific quality of life Scale and the caregiver quality of life questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 80 patients, 50(62.5%) were males and 30(37.5%) were females. The overall mean age was 61.46±11.80 years, and 56(70%) were aged >55 years. Among the patients, speaking power, mobility and mood were more affected with mean levels of 15.51±8.63, 22.63±8.33 and 19.08±7.05, respectively. The domains of social role, self-care and upper extremity function were also affected with mean values of 19.022±7.06, 15.71±8.81 and 18.88±7.02, respectively. Among the caregivers, the levels of physical wellbeing and functional wellbeing were high 15.07±5.65 and 15.35±5.76, respectively. There were differences in terms of age and gender but the difference was not significant (p>0.05). CONCLUSIONS: The quality of life of stroke survivors was low, and that of caregivers was also quite compromised.

Clinically significant findings of high-risk mutations in human SLC29A4 gene associated with diabetes mellitus type 2 in Pakistani population.

This study conducted an in-depth analysis combining computational and experimental verifications of the deleterious missense mutations associated with the SLC29A4 protein. The functional annotation of the non-synonymous single nucleotide polymorphism (nsSNPs), followed by structure-function analysis, revealed 13 single nucleotide polymorphisms (SNP) as the most damaging. Among these, six mutants P429T/S, L144S, M108V, N86H, and V79E, were predicted as structurally and functionally damaging by protein stability analysis. Also, these variants are located at evolutionary conserved regions, either buried, contributing to the structural damage, or exposed, causing functional changes in the protein. These mutants were further taken for molecular docking studies. When verified via experimental analysis, the SNPs M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) showed an association with type 2 diabetes mellitus (T2DM). Minor allele frequency for rs149798710 (A > G) was 0.23 in controls, 0.29 in metformin responders, 0.37 in metformin non-responder, for rs151039853 (A > C) was 0.21 in controls, 0.28 in metformin responders, 0.36 in metformin non-responder and for rs17854505 (T > A) was 0.20 in controls, 0.25 in metformin responders, 0.37 in metformin non-responder. Hence, this study concludes that SLC29A4 M108V (rs149798710), N86H (rs151039853), and V79E (rs17854505) polymorphisms were associated with the increased risk of T2DM as well as with the increased risk towards the failure of metformin therapeutic response in T2DM patients of Pakistan. Communicated by Ramaswamy H. Sarma.

Enteric Fever: Diagnostic Dilemma Encountered in Domperidone-Induced Neuroleptic Malignant Syndrome.

Enteric fever is a multisystem illness caused by Salmonella Typhi and Salmonella Paratyphi, and it is associated with a spectrum of conditions ranging from minor cases of diarrhea and low-grade fever to a potentially fatal illness that can lead to gastrointestinal (GI) perforation, hemorrhage, central nervous system (CNS) involvement. Neuroleptic malignant syndrome (NMS) is predominantly described as an idiosyncratic reaction to neuroleptic medications. However, it has also been associated with a variety of drugs that reduce dopaminergic activity. In this report, we present the case of a young woman who had enteric fever and was prescribed IV ceftriaxone and domperidone. She subsequently developed NMS secondary to domperidone. We highlight the challenges faced when dealing with two potentially lethal medical conditions presenting concurrently and their overlapping symptoms. The patient was treated for both of the conditions and recovered completely.

Frequencies of Beta Thalassemia Mutations Show Different Pattern in Bannu Region than Other Parts of Pashtun Population in Khyber Pakhtunkhwa Province Pakistan.

PURPOSE: ß-Thalassemia arises as result of mutations in HBB gene, influencing the globin production which results in hypochromic and microcytic anaemia. The present study was aimed to investigate the occurrence of six common ß-thal mutations, its inheritance pattern, frequency, and consanguinity in parents of Bannu region Khyber Pakhtunkhwa (KP) province, Pakistan. Conducting such studies may impart important information about thalassemia prevention like prenatal diagnosis (PND), carrier screening and genetic counselling which may be helpful in controlling the suspected births. METHODS: During the study, 250 blood samples were retrieved from different families comprising of one transfusion dependent child and sporadic patients from different areas of Bannu region. The collected blood samples were investigated to see if there is any common mutations which may trigger ß-Thalassemia employing amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) approach. RESULTS: Amongst the studied mutation in District Bannu, frame shift codons (FSC) 8/9 (+ G) (HBB: c.27_28insG) was observed to be the most common mutation followed by Codons 41/42 (- TTCT), IVS-I-5(G > C) and FSC 5 (- CT) having frequencies of 42, 26, 19 and 13 respectively. The results obtained by the present study were found different from previous studies demonstrated from other Pashtun regions of KP, showing heterogeneity in frequencies of known mutations. CONCLUSION: These observations may help in implementing parental meetings about disease recurrence in future, large scale mutation screening, and prenatal diagnosis in the whole Pashtun ethnicity including District Bannu.

The oracle study - fibromyalgia, prevalence and severity in the hospital setting in the Pakistani population.

OBJECTIVE: To assess the prevalence and severity of fibromyalgia in hospital-visiting patients. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July, 2018, to January, 2019, and comprised patients aged 18-75 years of either gender. Demographic information, comorbidities and previous medications were recorded for each patient. The modified American College of Rheumatology preliminary diagnostic criteria 2010-11 for fibromyalgia diagnosis. If diagnosed, the fibromyalgia impact questionnaire was administered to assess its severity. Data was analysed using SPSS 25. RESULTS: Of the 750 hospital-visiting patients, fibromyalgia was diagnosed in 250(33.3%); 190(76%) of them being females (p<0.0001). Comorbidities, age and increased elevated body mass index were significantly associated with fibromyalgia. Severity was not influenced by comorbidities, marital status, education or economic status (p>0.05). Menarche at a later age and menstrual irregularity were associated with fibromyalgia severity (p<0.05). CONCLUSIONS: The hospital-based prevalence of fibromyalgia was found to be high, especially among females.

Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial.

Objective This trial aimed to evaluate the safety and efficacy of pre-exposure prophylaxis (PrEP) with various hydroxychloroquine (HCQ) doses against a placebo among healthcare personnel (HCP) with high-risk exposure to coronavirus disease 2019 (COVID 19). Methods A phase II, randomized, placebo-controlled trial was conducted including 200 subjects with no active or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (antibody testing and reverse transcription-polymerase chain reaction (RT-PCR) were taken at the time of enrollment). Subjects of experimental groups one to three received HCQ in various doses and the control group received a placebo. The study outcomes in terms of safety and efficacy were monitored. Participants exhibiting COVID-19 symptoms were tested for SARS-CoV-2 during the study and by the end of week 12 with RT-PCR or serology testing (COVID-19 IgM/IgG antibody testing). Results Out of the total participants, 146 reported exposure to a confirmed COVID-19 case in the first month, and 192 were exposed by week 12 of the study. Moreover, the precautionary use of personal protective equipment (PPE) significantly varied; initially more than 80% of the exposed HCPs were not ensuring PPE being used by the patients treated by them, which gradually developed over time. Mild treatment-related side effects were observed among the interventional and placebo arm patients. There was no significant clinical benefit of PrEP with HCQ as compared to placebo (p>0.05). Conclusion It is concluded that the PrEP HCQ does not significantly prevent COVID-19 among high-risk HCPs.

A cross sectional study to assess nasal carriage of methicillin resistant Staphylococcus aureus in healthcare professionals in a tertiary care hospital.

OBJECTIVE: To determine the nasal carriage of staphylococcus aureus and methicillin-resistant staphylococcus aureus among healthcare workers in a tertiary care setting. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April to July 2018, and comprised healthcare workers at the institution. Nasal swabs were collected and cultured on Mannitol salt agar. Mannitol fermenting colonies which were gram-positive cocci, catalase-positive and coagulase-positive were identified as staphylococcus aureus. Antibiotic susceptibility test was performed by modified Kirby-Bauer disc diffusion method. Methicillin resistance was detected using cefoxitin disc diffusion method. Data was analysed using SPSS 23. RESULTS: Of the 210 nasal swabs, 52(24.76%) had a staphylococcus aureus growth, and of them, 15(7.1%) were methicillin-resistant. No association could be established with either any single category of healthcare worker or an inter-department variation (p>0.05). Likewise, there was no association with age, gender, duration of service, smoking, co-morbidities, use of antibiotics in the preceding six months, treating a patient with methicillin-resistant staphylococcus aureus in the preceding six months and hospitalisation in the preceding year (p>0.05). CONCLUSIONS: The frequency of nasal carriage of methicillin resistant staphylococcus aureus amongst healthcare workers was regardless of the nature of their professional engagement.

DAR-GRACE: Diabetes and Ramadan: glycaemic control, physician counselling and patient practices -experience from a tertiary care hospital in Pakistan.

OBJECTIVE: To identify patient practices and knowledge pertaining to Ramadan fasting and to see whether physicians were providing adequate counselling and adjusting medications accordingly. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from June to August 2018, and comprised diabetic patients who fasted during Ramadan. A questionnaire was designed to assess patients' knowledge, risk category, pre-Ramadan counselling, medication adjustment, lifestyle changes, pre- and post- Ramadan glycated haemoglobin levels, and complications during Ramadan. Data was analysed using SPSS 23. RESULTS: Out of 272 diabetics, 176(64.7%) were females. Mean number of fasts kept were 22±10.61. Pre-Ramadan 120(44.1%) patients consulted their physicians and 105(87.5%) of them received relevant counselling. Medications were adjusted in only 30 (25%) such cases. Overall, 41(15.1%) patients were in the high risk category, while 109(40.1%) and 122(44.9%) were in the moderate and low-risk categories. During the month, 17(6.25%) were hospitalised due to diabetes-related complications. Glycated haemoglobin levels fell significantly (p<0.0001). CONCLUSIONS: Anomalous patient behaviours and suboptimal physician practices were noticed.

Assessment of red cell distribution width, glycaemic control and diabetes related complications - the ARDENT Study.

OBJECTIVE: To assess the association of red cell distribution width with glycaemic control and the presence of complications in diabetes patients. METHODS: The cross-sectional study was done at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from September to November 2017, and comprised patients with type 2 diabetes. Clinical and demographical characteristics were documented and they were subjected to complete blood count, red cell distribution width, glycated haemoglobin, fasting and random blood glucose, lipid profile, urea and creatinine. The presence of complications were assessed during clinical examination. SPSS 20 was used for data analysis.. RESULTS: There were 349 patients with a mean age of 53.14±11.77 years. The mean duration of diabetes was 8.36±6.64 years and mean glycated haemoglobin was 9.05±1.93. Red cell distribution width was significantly associated with the duration of diabetes, hypertension, macrovascular and microvascular complications and extent of glycaemic control (p<0.0001 each). A statistically significant linear relationship was observed between red cell distribution width and the number of macrovascular and microvascular complications (p<0.0001) and glycated haemoglobin (p<0.0001). Mean red cell distribution width was 13.94±1.66, 14.72±1.38, and 15.76±1.55 for optimal control, borderline control and poor control respectively. This linear incremental pattern was statistic ally significant (p<0.0001). CONCLUSIONS: The linear association of red cell distribution width with glycated haemoglobin may enable its use as a measure of the extent of hyperglycaemia.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

The ATONE study - assessment of diabetes knowledge in individuals with type 2 diabetes in the Pakistani population.

OBJECTIVE: To evaluate knowledge of diabetes using diabetes knowledge questionnaire in diabetic patients. METHODS: The cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October to December 2017, and comprised subjects aged >20 years with a diagnosis of type 2 diabetes. The modified version of diabetes knowledge questionnaire was used for data collection. It had 24 questions concerning patient's diabetes knowledge and self-care practices. One point was given for each correct answer. The highest achievable score was 24. A total score of ?12 was considered suggestive of adequate knowledge. SPSS 23 was used for data analysis. RESULTS: Of the 401 subjects, 175 (43.6%) were males and 226 (66.4%) were females. The overall mean age was 52.9 }12.3 years, and mean duration of diabetes was 7.95}6.7 years. The mean score on the questionnaire was 9.97}3.93. Only 135(33.7%) patients showed adequate knowledge of the disease. Factors having positive correlation with the score were patient's urban background, level of literacy and their socioeconomic status (p<0.05 each). The duration of diabetes and the control of diabetes had no influence on the scores (p>0.05 each). CONCLUSIONS: Knowledge about diabetes was found to be generally poor among diabetics.

Effects of SLC22A2 (rs201919874) and SLC47A2 (rs138244461) genetic variants on Metformin Pharmacokinetics in Pakistani T2DM patients.

OBJECTIVE: To determine the frequencies of single nucleotide polymorphisms rs201919874 and rs138244461 in genes SLC22A2 and SLC47A2 respectively in Pakistani diabetes patients in order to characterise the genetic variants and determine their association with the pharmacokinetics of metformin. METHODS: The case-control study was conducted at the International Islamic University, Islamabad, Pakistan, from June 2016 to June 2017, and comprised genotypes of diabetic cases and matching controls which were determined following allele-specific polymerase chain reaction. Cases were further divided into Group A and Group B. The former consisted of diabetics who were on monotherapy of metformin, while the latter consisted of diabetics treated with a combination of metformin and sulfonylureas. In-silico analysis was performed to verify the effect of single nucleotide polymorphisms rs201919874 and rs138244461 on the structure of genes. Association was statistically determined using SPSS 18. RESULTS: Of the 1200 subjects, 800(66.6%) were cases and 400(33.3%) were controls. Among the cases, 400(50%) each were in Group A and Group B. Significant difference was observed in the distribution of rs201919874 between Group A and controls (p<0.05) and between Group B and controls (p<0.05) for heterozygous genotypic frequency and for allelic frequency. Conversely, statistically significant difference was observed in rs138244461 (p<0.05) for all genotypic and allelic frequencies. Genotypes were significantly associated with glycated haemoglobin, random and fasting glucose levels in Group A compared to Group B (p<0.05). In-silico analysis showed that both single nucleotide polymorphisms were expected to create significantly damaging structural changes in domains and helix (p<0.05 each). CONCLUSIONS: Both exonic single nucleotide polymorphisms were found to be associated with the pharmacokinetics of metformin.

Foot-care behaviour amongst diabetic patients attending a federal care hospital in Pakistan.

OBJECTIVE: To assess foot-care behaviour in diabetics attending a tertiary care hospital, and to see if there are any influencing factors. METHODS: The cross-sectional descriptive study was conducted from September to November 2017 at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised diabetes patients either admitted to the wards or attending the outpatient clinics. Foot-care behaviour was assessed through the validated Nottingham Assessment of Functional Foot-care scale. A score over 50 demonstrated adequate foot-care behaviour. The score was correlated with several variables. SPSS 23 was used for data analysis. RESULTS: Of the 400 individuals, 238(59.5%) were females and 162(40.5%) were males. The overall mean age was 52.71}11.84 years. Of the total, 228(57%) had never received any education on proper foot-care; 289(72.3%) had a scale score of less than or equal to 50. Urban or rural residence, monthly income, literacy level, family history of diabetes, and previous foot-care education provided by the healthcare provider were significant factors associated with good foot-care behaviour (p<0.05 each). CONCLUSIONS: A majority of the patients demonstrated inadequate foot-care behaviour..

Evaluation of the rs3088442 G>A SLC22A3 Gene Polymorphism and the Role of microRNA 147 in Groups of Adult Pakistani Populations With Type 2 Diabetes in Response to Metformin.

OBJECTIVES: Type 2 diabetes is a complex genetic disorder, and a large number of genetic polymorphisms may be involved in its pathogenesis. Pharmacologically, type 2 diabetes can be treated with 9 different approved classes of drugs, but metformin is suggested as the first line of therapy, followed by sulfonylureas. METHODS: This was a case-control study consisting of 300 metformin responders and 300 metformin nonresponders in patients with type 2 diabetes and 300 healthy Pakistani subjects. Genotyping of the SLC22A3 G>A polymorphism was performed by allele-specific polymerase chain reaction (PCR) for microRNA 147 expression; real-time polymerase chain reaction was used, and expressional analysis of SLC22A3 was done by semiquantitative polymerase chain reaction. RESULTS: GA and AA genotypes were highly significantly associated with the drug treatments when compared with controls. A statistically significant difference was observed in the distribution of the SLC22A3 A allele between healthy subjects and patients with type 2 diabetes. When odds ratios were adjusted for glycated hemoglobin levels and postprandial and fasting blood glucose levels, our findings showed that the overexpression of allele A of the rs3088442 G>A variant may act as a protective allele and is associated with the clinical response to metformin. microRNA 147 expression was found to be increased in patients who were metformin responders compared with the nonresponder group and controls. mRNA expression of SLC22A3 was significantly reduced in patients taking metformin as compared to other groups. CONCLUSIONS: These results suggested that the SLC22A3 rs3088442 at position 2282 A allele may confer metformin clinical responses in patients with type 2 diabetes in the Pakistani population. Overexpression of microRNA 147 is associated with a downward expression of the SLC22A3 gene in patients who have type 2 diabetes.

Association of dyslipidaemia in patients with varying degrees of Vitamin D deficiency in the Asian population.

OBJECTIVE: To investigate the associations of dyslipidaemia with varying levels of 25 hydroxy vitamin D3 deficiency. METHODS: This cross-sectional study was conducted at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from July 2016 to January 2017, and comprised patients having varying levels of 25 hydroxy vitamin D3 deficiency. Patients were stratified according to the severity of deficiency and had their serum fasting lipid profiles measured. SPSS 20 was used for data analysis. RESULTS: Of the 175 participants, 124(70.9%) were female and 51(29.1%) were male. The overall mean age of the patients was 47.7±12.2 years (range: 18-65 years). A very strong inverse correlation was found between vitamin D levels and low-density lipoprotein cholesterol (p<0.001) and a similar trend was obtained for vitamin D and total cholesterol (p<0.001). With regards to triglycerides, a modest inverse correlation was found (p=0.05). No significant association was documented between 25 hydroxy vitamin D3 levels and high-density lipoprotein cholesterol (p=0.3). CONCLUSIONS: An inversely proportional relationship was found between total cholesterol, low-density lipoprotein cholesterol and triglycerides against varying levels of vitamin D deficiency.