Publications by authors named "Iqbal Azam"

98 Publications

Translation and validation of the Urdu version of the European organization for research and treatment of cancer core quality of life questionnaire (EORTC QLQ-C30) and brain module (QLQ-BN20) in primary brain tumor patients.

J Patient Rep Outcomes 2021 Sep 6;5(1):79. Epub 2021 Sep 6.

Department of Surgery, Aga Khan University Hospital, Stadium Road, Karachi, 74800, Pakistan.

Introduction: This study translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) and Brain Module (QLQ-BN20) amongst patients with primary brain tumors (PBT) in Pakistan, and assessed the correlation of QoL with resilience, depression, and anxiety.

Methods: Translation of the EORTC QLQ-C30 and QLQ-BN20 was performed as per EORTC guidelines. A survey comprising of Urdu translations of EORTC QLQ-C30, QLQ-BN20, Wagnild and Young Resilience Scale (RS-14) and Hospital Anxiety and Depression Scale was administered to patients with PBT at a tertiary care hospital in Pakistan. Reliability (via Cronbach alpha), content validity index (CVI) scores, construct validity, and inter-scale correlations were assessed.

Results: Our sample consisted of 250 patients with PBT, most commonly glioma (46.8%) and meningioma (21.2%). All patients were able to understand the Urdu translations. The Cronbach alphas for the QLQ-C30 and the QLQ-BN20 were 0.860 and 0.880, respectively. The CVI scores for clarity and relevance were high for both the EORTC QLQ-C30 (0.98 and 0.96, respectively) and the QLQ-BN20 tool (0.81 and 0.95, respectively). The global QoL domain (EORTC QLQ-C30) showed significant positive correlations with resilience (r = 0.422), and significant negative correlations with depression (r =  - 0.541) and anxiety (r =  - 0.502). Strong inter-scale correlations were observed between physical functioning and insomnia (r =  - 0.690) and role functioning and insomnia (r =  - 0.641).

Conclusion: Our study confirms the Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 as valid clinical tools for the measurement of QoL in primary brain tumors patients within the cultural and socioeconomic context of Pakistan.
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http://dx.doi.org/10.1186/s41687-021-00354-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421474PMC
September 2021

Resilience and its associated factors in head and neck cancer patients in Pakistan: an analytical cross-sectional study.

BMC Cancer 2021 Aug 3;21(1):888. Epub 2021 Aug 3.

Department of Surgery, Aga Khan University Hospital, Stadium Road, Karachi, 74800, Pakistan.

Introduction: The study aimed to assess resilience and its associated factors in head and neck cancer patients, post-treatment in a low middle income country (LMIC) such as Pakistan.

Methods: An analytical cross-sectional study was conducted from November 2019 to May 2020 among head and neck cancer patients aged at least 18 years at the largest private tertiary care hospital, in Karachi, Pakistan. Information regarding their resilience scores was collected through Wagnild and Young's Resilience scale that comprises of 14 items (RS-14). Moreover, depression and anxiety were also assessed via Hospital Anxiety and Depression Scale (HADS) and social support was assessed by Enriched Social Support Instrument (ESSI).

Results: The data was analyzed by linear regression modeling. Unadjusted and adjusted beta coefficients with 95% CI were reported. A total of 250 head and neck cancer patients were recruited, 79% of them were males. Mean age of the patients was 51.59 years with 93% having high social support and only 8% having severe depression and 3% having severe anxiety. After adjusting for the covariates in multivariable analysis resilience was associated with severe depression (- 17[- 20.98,-12.93]) or borderline depression (- 4[- 8.41,-0.39]), severe anxiety (- 11 [- 17.88,-4.18]), low social support (- 6[- 9.62,-1.71]), having family members of > 6 in the household (- 2[- 4.31,-0.29), smokeless tobacco users post- treatment (10[5.79, 14.45]), and those who underwent tracheotomy (- 4[- 7.67,-0.21]). There was a significant interaction between education and role in the family (decision maker).

Conclusion: In Pakistan, a South Asian LMIC, collectivist culture prevails, family ties are greatly promoted thus resilience and social support is highly prevalent in head and neck cancer patients resulting in lower prevalence of depression and anxiety. Our study highlights that higher resilience is prevalent among small families less than six members, as the welfare of the individual is prioritized over multiple needs of the family. Formal Education and role in household/decision making power are effect modifiers in our study, demonstrating its protective effect on the mental health of head and neck cancer patients. High resilience scores were reported among current smokeless tobacco users as compared to quitters post treatment. Resilience-building interventions should be formulated to aid head and neck cancer patients to cope with the disease and its sequel.
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http://dx.doi.org/10.1186/s12885-021-08624-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330007PMC
August 2021

Influence of intrauterine growth status on aortic intima-media thickness and aortic diameter in near-term fetuses: a comparative cross-sectional study.

J Dev Orig Health Dis 2021 Jun 15:1-8. Epub 2021 Jun 15.

Maternal Fetal Medicine Unit, Department of Obstetrics and Gynaecology, Aga Khan University, Pakistan.

Intrauterine undernutrition may lead to fetal vascular programming. We compared abdominal aortic intima-media thickness (aIMT) and aortic diameter (aD) between appropriate for gestational age (AGA) and growth-restricted fetuses (GRF). We recruited 136 singleton fetuses at 34-37 weeks of gestation from Fetal Medicine Unit of Aga Khan University Hospital, Karachi (January-November 2017). Subjects were classified as AGA (n = 102) and GRF (n = 34) using INTER-GROWTH 21st growth reference and standard ultrasound protocol. Their far- and near-wall aIMT and aD were compared after adjustment of maternal age, first-trimester body mass index, fetal gender, hypertension and hyperglycemia in pregnancy. As the severity of growth restriction increased in GRF, aIMT and aD showed an increasing and a decreasing trend, respectively. Both far- and near-wall aIMT in GRF [(adj. β = 0.082, 95% confidence interval [CI] 0.042-0.123) and (adj. β = 0.049, 95% CI 0.010-0.089)] were significantly greater with reference to AGA fetuses. GRF subgroup analysis into small for gestational age (SGA) fetuses and intrauterine growth restricted (IUGR) revealed highly significant difference between AGA and IUGR for far (0.142 mm, P-value < 0.001) and near-wall aIMT (0.115 mm, P-value < 0.001) and marginally significant aD difference (0.51 mm, P-value 0.05). These findings suggest that the extent of fetal aortic remodelling is influenced by the severity of growth restriction. Hence, the targeted interventions for the cardiovascular health promotion of IUGR and SGA born neonates are desirable during early childhood, particularly in set ups with high prevalence of low birth weight babies.
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http://dx.doi.org/10.1017/S2040174421000295DOI Listing
June 2021

Frequency and determinants of vitamin D deficiency among premenopausal and postmenopausal women in Karachi Pakistan.

BMC Womens Health 2021 05 10;21(1):194. Epub 2021 May 10.

School of Medicine, Adelaide Medical School, University of Adelaide, Adelaide, Australia.

Background: Vitamin D deficiency is becoming a serious public health problem, even in sun-drenched cities like Karachi, Pakistan. We investigated the prevalence of vitamin D deficiency and its association with sociodemographic characteristics, anthropometric measures, and lifestyle factors among premenopausal and postmenopausal women (n = 784).

Methods: Face-to-face interviews were conducted to collect information and serum concentrations of 25-hydroxyvitamin D were measured after the interviews.

Results: A total of 57% of women were vitamin D deficient with higher vitamin D deficiency found among premenopausal women (64.7%) compared to postmenopausal women (49%). The median serum concentrations of 25-hydroxyvitamin D (IQR) were 16.7 ng/ml (IQR 9.8-30.0). Factors associated with vitamin D deficiency were lower socioeconomic status (OR 2.00; 95% CI 1.15-3.48), younger age with highest vitamin D deficiency found in < 35 years of age group (OR 3.11; 95% CI 1.76-5.51), and winter season (OR 1.51, 95% CI 1.07-2.15) after adjusting for multiple confounders. The use of vitamin D supplement (OR 0.59, 95% CI 0.38-0.92) and vigorous exercise (OR 0.20, 95% CI 0.05-0.80) were protective against vitamin D deficiency.

Conclusions: The study shows a high prevalence of vitamin D deficiency, with detrimental health effects, among younger women belonging to lower socioeconomic status and during the winter season. The use of vitamin D supplements and vigorous exercise were protective measures. Public health campaigns are needed for education and awareness about vitamin D deficiency to improve vitamin D status for younger women living in poor environments.
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http://dx.doi.org/10.1186/s12905-021-01339-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108729PMC
May 2021

Lack of association of HFE gene polymorphism with high body iron status in Pakistani patients with type 2 diabetes mellitus.

J Pak Med Assoc 2021 Feb;71(2(B)):608-613

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

Objective: The Aim of this study was to investigate the relationship of 3 common polymorphisms in the HFE gene (C282Y, H63D and S65C) with high body iron status in a population of Pakistani subjects with type 2 diabetes mellitus (DM) and to explore if there is any novel mutation in HFE gene in a sample of Pakistani subjects with type 2 DM.

Methods: In a case-control design, 200 healthy controls and 200 consecutive adult subjects with type 2 DM (both gender; age range of 30-70 years) were enrolled with informed consent. Their serum samples were analyzed for body iron status (ratio of concentration of soluble transferrin receptor to ferritin concentration). DNA from blood was screened for HFE gene polymorphisms via polymerase chain reaction, followed by restriction fragment length polymorphism or via Sanger sequencing to identify any novel mutation(s) in HFE gene.

Results: We found that there was lack of any association between HFE polymorphism and body iron status in Pakistani subjects with type 2 DM and healthy controls. H63D was the most common polymorphism found in this population. Single base substitution of G nucleotide instead of C at the codon position 187 in the HFE gene exon 2 was discovered in one subject with DM. There was also a lack of association between D allele (variant allele of H63D) and type 2 DM. A significant relationship was found between CG genotype and abnormal albuminuria in subjects with type 2 DM (p = 0.036).

Conclusion: In conclusion, HFE gene polymorphism is not associated either with high body iron status or type 2 DM in a hospital based Pakistani population and variant allele of H63D polymorphism appears to be associated with diabetic nephropathy.
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http://dx.doi.org/10.47391/JPMA.563DOI Listing
February 2021

Resilience and its associated factors in brain tumor patients in Karachi, Pakistan: An analytical cross-sectional study.

Psychooncology 2021 Jun 10;30(6):882-891. Epub 2021 Mar 10.

Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan.

Objectives: This study assessed resilience in brain tumor patients at a tertiary care hospital in Pakistan (a lower middle-income country; LMIC) and explored its relationship with patients' sociodemographic factors, clinical characteristics, social support, and mental health.

Methods: A cross-sectional survey was conducted amongst adult (≥18 years) patients with brain tumor at the Aga Khan University Hospital, Pakistan. Resilience was assessed by Wagnild and Young's Resilience Scale, and patients' psychosocial characteristics by the Hospital Anxiety and Depression Scale and the Enriched Social Support Instrument.

Results: A total of 250 patients were included (mean age: 44 years; 68% males), with majority (97.6%) having high social support and only 4.4% and 2% having symptomatic depression and anxiety, respectively. On multivariable linear regression adjusted for covariates, lower resilience was associated with not being involved in household decision-making (Adjusted Beta Coefficient: 4.58 [95% Confidence Interval:-7.59, -1.56]), not currently working (-2.80 [-4.61, -0.99]), undergoing multiple neurosurgical interventions such as tumor biopsies or resections (-8.64 [-13.11, -4.16]), receiving chemotherapy (-5.17 [-9.51, -0.83]) or combination adjuvant therapy (-2.91 [-5.14, -0.67]), low social support (-7.77 [-13.73, 1.81]), mild depression (-13.00 [-17.00,-8.99]) or symptomatic depression (-19.79 [-24.69, -14.89]), and mild anxiety (-4.24 [-7.98, -0.50]).

Conclusion: Our study highlights the function of familial/household role and working status in mediating resilience, and demonstrates the well-known protective effect of resilience for mental health in brain tumor patients in Pakistan, a South-Asian LMIC. These findings are of clinical relevance with regards to the development of culture-specific evidence-based resilience-building interventions that may help patients with brain tumors to cope with the psychological distress of cancer.
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http://dx.doi.org/10.1002/pon.5661DOI Listing
June 2021

Perceptions, knowledge and attitudes towards the concept and approach of palliative care amongst caregivers: a cross-sectional survey in Karachi, Pakistan.

BMC Palliat Care 2020 Nov 26;19(1):180. Epub 2020 Nov 26.

School of Nursing and Midwifery, SONAM, Aga Khan University and Hospital, Karachi, Pakistan.

Background: Limited comprehension of the concept of palliative care and misconceptions about it are barriers to meaningful utilisation of palliative care programs. As caregivers play an integral role for patients with terminal illness, it is necessary to assess their perceptions and attitudes towards the palliative care approach.

Method: A cross-sectional survey was conducted. Data was collected from the Aga Khan Hospital in-patient and out-patient departments and home-based palliative care services. All adult caregivers who met the inclusion criteria and consented, completed a questionnaire till the sample size was reached. Univariate and multivariate multivariable analysis was done and results were reported as crude prevalence's, crude and adjusted prevalence ratios with 95% confidence intervals using Cox-proportional hazard algorithm. Mean difference of knowledge and attitude scores by caregiver variables were assessed using one-way ANOVA. SPSS version 18 was used and a p-value of less than 5% was treated as significant.

Results: Out of 250 caregivers more than 60% were 40 years or less, majority were males and at least graduates. Approximately 70% of the respondents agreed with the statement that the person suffering from cancer should be informed about the diagnosis and disease progression. About 45% (95% C.I.: 39.03, 51.37%) of the study respondents had enhanced understanding about palliative care. Individuals under 40 years old, those with an education level of at least grade 10, children or relatives were found to have significantly more enhanced knowledge about palliative care. The majority believed that the patient should be informed about the diagnosis and should be facilitated to carry out routine activities and fulfill their wishes.

Conclusion: Nearly half of the caregivers had enhanced understanding of the palliative care approach. They showed consistent understanding of two foundational aspects indicating correct knowledge across age groups, gender, education level, and relationship with the patient. Firstly, that palliative care should be offered to everyone suffering from a terminal illness and, secondly, that this approach encompasses not just physical, but also psychological and social needs of the patient and the family. These findings will help inform the establishment of a palliative care program that fills the gaps in comprehension and knowledge of caregivers.
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http://dx.doi.org/10.1186/s12904-020-00688-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694898PMC
November 2020

Depression among adult patients with primary brain tumour: a cross-sectional study of risk factors in a low-middle-income country.

BMJ Open 2020 09 9;10(9):e032748. Epub 2020 Sep 9.

Psychiatry, Aga Khan University, Karachi, Pakistan.

Objective: The prevalence of depression among patients with primary brain tumour ranges from 15% to 40% globally. Several individual and clinical factors contribute to the development of depression. However, their association with depression in Pakistani setting has not yet been assessed. Thus, we aim to study the factors associated with depression among adult patients with primary brain tumour at a tertiary care hospital in Karachi, Pakistan.

Study Design: A prospective cross-sectional study.

Setting: This study was conducted at a tertiary care hospital of Karachi, Pakistan.

Participants: This study included 132 patients with confirmed diagnosis of primary brain tumour (initially diagnosed on MRI of the brain with contrast and later confirmed on histology of surgical specimen) in various stages of treatment.

Primary Outcome: The primary outcome of this study was to assess depression and its associated factors among adult patients with primary brain tumour. Depression was assessed using a validated screening tool Patient Health Questionnaire-9 (PHQ-9). Scores of 10-27 on PHQ-9 were indicative of screen positive for depressive symptoms. A set of the structured pre-tested questions was used to evaluate patient-related, tumor-related and treatment-related factors.

Results: Fifty-one (39%, CI: 33.33-46.94) patients in our study screened positive for depressive symptoms on PHQ-9. There was a significant association between depressive symptoms and Karnofsky Performance Scores (KPS) (prevalence ratio: 3.25 and CI: 1.87-5.62) after controlling covariates. Propensity scores predicted a positive association between KPS (functional status) and unemployment, treatment stage, and tumour recurrence. Tumor-related and treatment-related factors including tumour grade, location, type and hemispheric lateralisation were found insignificant.

Conclusion: Depression is common in patients with primary brain tumour. Impaired functional status has a direct impact on depression in these patients. Incorporating the psychosocial domain earlier in the course of treatment needs to be considered for better neuro-oncology management of patients with primary brain tumour.
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http://dx.doi.org/10.1136/bmjopen-2019-032748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482499PMC
September 2020

Early intervention physical therapy using "Parent Empowerment Program" for children with Down syndrome in Pakistan: A feasibility study.

J Pediatr Rehabil Med 2020 ;13(3):233-240

Department of Rehabilitation and Regenerative Medicine, Columbia University Medical Center, New York, NY, USA.

Purpose: The aim of this study was to evaluate the feasibility and effectiveness of the Parent Empowerment Program (PEP) to help caretakers deliver a home program to promote developmental activities and gross motor function in their children with Down syndrome.

Methods: Parents attended a 14-month program with training sessions 1-4 times a month. Outcomes were measured using a change in the Gross Motor Function Measure (GMFM-88) at baseline and assessment one.

Results: Forty-eight families participated in the PEP. Children's mean age was 16.2 ± 10.8 months. There were significant changes in GMFM-88 scores between baseline and assessment one; t (30) =-9.158, p< 0.001; 95% CI -14.6 - -22.9. Previous hospitalization significantly affected GMFM scores.

Conclusion: This study describes a clinically applied research that focuses on program design, development and evaluation. Findings indicate that the PEP is effective in improving gross motor function in children with Down's syndrome in Pakistan. Parents were satisfied with the program outcomes and were able to cope with the requirements at home. The PEP had favorable outcomes and may be an effective method to support PT services in resource poor countries.
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http://dx.doi.org/10.3233/PRM-190605DOI Listing
September 2021

Reliability and Validity of WATCH: Warwick Assessment InsTrument for Clinical TeacHing.

J Coll Physicians Surg Pak 2020 Jun;30(6):633-637

Department of Community Medicine, Faculty of Health Sciences, The Aga Khan University, Karachi, Pakistan.

Objective: To determine the reliability, validity, feasibility, acceptability and perceived educational impact of WATCH: Warwick Assessment insTrument for Clinical teacHing among doctors in Pakistan.

Study Design: Cross-sectional research study.

Place And Duration Of Study: The College of Physicians and Surgeons, Pakistan, from September 2018 to August 2019.

Methodology: Postgraduate trainees were asked to rate the clinical teaching sessions, using WATCH, which consists of 15 items. Percentage was used to calculate gender and participation from different specialties. Inter-item correlations of 15 items with individual mean scores, standard deviations and Cronbach's Alpha were reported, including Friedman test, in order to observe the scores across multiple conditions. The Hotelling's T2 test was used to test whether the answers provided by the study participants to the questionnaire were equal. Construct validity was determined using factor analysis while feasibility, acceptability, and educational impact was evaluated by seeking participants' feedback on five semi-structured questions.

Results: More than 80% ranked WATCH from good to excellent.  Oveall 8 items were perceived as excellent, while 7 items received rating of good. Inter-item correlation ranged from 0.61 to 0.81. Cronbach Alpha was reported to be 0.975, with significant difference in mean scores of different items (Friedman's Chi-Square=4285.54; p<0.001). The Hotelling's T2 test (21598.871 with F=185.249, df=14,2654; p<0.001) indicated that the mean values of the responses of different questions in the instrument were statiscally different. Factor analysis indicated one factor accounting for 73.97 of variance. The majority (93%) of the participants found the instrument easy to complete, most participants (91.5%) indicated it as an acceptable method of assessment, and majority (90.8%) perceived that it can improve clinical teaching.

Conclusion: WATCH demonstrated valid, reliable, feasible, and acceptable results for assessment of teaching of medical doctors and it can be used for providing feedback and rewarding teachers who excel in teaching. Key Words: Clinical teaching, Validity, Reliability, Feasibility, Medical students, Residents, Doctors.
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http://dx.doi.org/10.29271/jcpsp.2020.06.633DOI Listing
June 2020

Patient Delay in Breast Cancer Diagnosis in Two Hospitals in Karachi, Pakistan: Preventive and Life-Saving Measures Needed.

JCO Glob Oncol 2020 06;6:873-883

Adelaide Medical School, University of Adelaide, Adelaide, Australia.

Purpose: Patients with breast cancer in Pakistan commonly present with advanced disease. The objectives of this study were to evaluate the frequency and length of delays in seeking medical consultation and to assess the factors associated with them.

Methods: Four hundred ninety-nine patients with newly diagnosed breast cancer were enrolled and interviewed over the period from February 2015 to August 2017. Information on sociodemographic factors, delay to medical consultation, stage of breast cancer at presentation, and tumor characteristics of the breast cancer were collected through face-to-face interviews and medical file review.

Results: The mean (standard deviation) age of patients with breast cancer was 48.0 (12.3) years. The mean (standard deviation) patient delay was 15.7 (25.9) months, with 55.2% of women detecting a breast lump but not seeking a medical consultation because of a lack of awareness about the significance of the lump. A total of 9.4% of the women decided to seek treatment initially using complementary and alternative medicine and traditional treatment; 9.4% of the women presented to a health care provider with a breast lump but no action was taken, and they were wrongly reassured about the lump without mammography or biopsy. For 26% of the women, the delay in presentation was caused by anxiety, fears and misconceptions regarding diagnosis and treatment, and other social factors including possible adverse effects on their relationship with their husband. Multivariable analysis showed a strong association of lower socioeconomic status (odds ratio [OR], 8.11 [95% CI, 2.46 to 26.69]) and late stage of breast cancer (OR, 4.83 [95% CI, 1.74 to 13.39]) with a patient delay of ≥ 3 months.

Conclusion: Patient delay is a serious problem in Pakistan. There is an urgent need for intensive and comprehensive breast cancer education that addresses the myths and misconceptions related to breast cancer.
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http://dx.doi.org/10.1200/GO.20.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328101PMC
June 2020

Risk factors for postpartum sepsis: a nested case-control study.

BMC Pregnancy Childbirth 2020 May 14;20(1):297. Epub 2020 May 14.

Global Women's Health, King's College, London, UK.

Background: The Majority (99%) of maternal deaths occur in low and middle-income countries. The three most important causes of maternal deaths in these regions are postpartum hemorrhage, pre-eclampsia and puerperal sepsis. There are several diagnostic criteria used to identify sepsis and one of the commonly used criteria is systematic inflammatory response syndrome (SIRS). However, these criteria require laboratory investigations that may not be feasible in resource-constrained settings. Therefore, this study aimed to develop a model based on risk factors and clinical signs and symptoms that can identify sepsis early among postpartum women.

Methods: A case-control study was nested in an ongoing cohort of 4000 postpartum women who delivered or were admitted to the study hospital. According to standard criteria of SIRS, 100 women with sepsis (cases) and 498 women without sepsis (controls) were recruited from January to July 2017. Information related to the socio-demographic status, antenatal care and use of tobacco were obtained via interview while pregnancy and delivery related information, comorbid and clinical sign and symptoms were retrieved from the ongoing cohort. Multivariable logistic regression was performed and discriminative performance of the model was assessed using area under the curve (AUC) of the receiver operating characteristic (ROC).

Results: Multivariable analysis revealed that 1-4 antenatal visits (95% CI 0.01-0.62). , 3 or more vaginal examinations (95% CI 1.21-3.65), home delivery (95% CI 1.72-50.02), preterm delivery, diabetes in pregnancy (95% CI 1.93-20.23), lower abdominal pain (95% CI 1.15-3.42)) vaginal discharge (95% CI 2.97-20.21), SpO2 < 93% (95% CI 4.80-37.10) and blood glucose were significantly associated with sepsis. AUC was 0.84 (95% C.I 0.80-0.89) which indicated that risk factors and clinical sign and symptoms-based model has adequate ability to discriminate women with and without sepsis.

Conclusion: This study developed a non-invasive tool that can identify postpartum women with sepsis as accurately as SIRS criteria with good discriminative ability. Once validated, this tool has the potential to be scaled up for community use by frontline health care workers.
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http://dx.doi.org/10.1186/s12884-020-02991-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227107PMC
May 2020

Estimation of the burden of out-of-hospital traumatic cardiac arrest in Karachi, Pakistan, using a cross-sectional capture-recapture analysis.

Int J Emerg Med 2020 May 14;13(1):26. Epub 2020 May 14.

School of Medicine, Johns Hopkins University, Baltimore, USA.

Background: The burden of trauma-related-out-of-hospital cardiac arrest (OHCA) in developing countries like Pakistan remains largely unexplored due to a lack of organized pre-hospital systems. In order to estimate the burden, we used a two-sample capture-recapture method which has been used in several domains to estimate difficult-to-count populations.

Methods: We obtained 3-month data from two sources: Records of two major EMS (emergency medical services) systems and five major hospitals providing coverage to the city's population. All adults with traumatic OHCA were included. Information on variables such as name, age, gender, date and time of arrest, cause of arrest, and destination hospital were obtained for these cases and data were compared to obtain a matched sample. Utilizing an equation and different levels of restrictive criteria, estimates were obtained for burden.

Results: The EMS records reported 788 and hospital records reported 344 cases of traumatic OHCA. The capture-recapture analysis estimated the annual traumatic OHCA incidence as 45.7/100,000 (95% CI: 44.2 to 47.3). Estimation of the burden from individual hospital or EMS records underestimated and calculated only 14.6% and 33.9% of the total burden, respectively. Most of the traumatic arrest victims had gunshot wound (GSW) (65.2%) followed by road traffic injuries (RTI) (20.8%).

Conclusion: The actual burden of traumatic OHCA in Pakistan is larger than the burden reported by either the hospitals or EMS services alone. Most of the cases occurred due to GSW and RTI. A multipronged approach is required to manage the problem; from prevention to developing organized trauma care systems and training lay responders in pre-hospital trauma care is vital.
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http://dx.doi.org/10.1186/s12245-020-00283-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227293PMC
May 2020

Adolescent food insecurity in rural Sindh, Pakistan: a cross-sectional survey.

BMC Nutr 2020 26;6:17. Epub 2020 Mar 26.

3School of Nursing and Midwifery, Aga Khan University, Stadium road, Karachi, 74800 Pakistan.

Background: Food insecurity (FI) is alarmingly high in developing countries including Pakistan. A quarter of Pakistan's population consists of adolescents yet there is no information on their experience of FI. FI at adolescent age have long term effect on mental and physical health hence we aimed to determine the prevalence of food insecurity (FI) among adolescents and compare it with household FI, and assess social determinants of adolescent FI.

Methods: A cross-sectional survey on 799 households with unmarried adolescents was conducted from September 2015 to June 2016 in three union councils of Hyderabad, Pakistan. Unmarried 10-19 years old girls and boys were interviewed regarding their FI status using Household Food Insecurity Assessment Scale (HFIAS). Household-level FI was also assessed by interviewing mothers of adolescents, and it was compared with adolescent's FI. Association of adolescent's FI with socio-demographic determinants was explored through Cox regression using STATA version 14.0. and prevalence ratios were estimated.

Results: FI was found among 52.4% of the adolescents compared to 39% of the households. Thirty percent of the adolescents were food insecure within the food secure households. Female adolescents were found to be less food insecure (Adjusted Prevalence Ratio (APR) 0.4 95% CI [0.3, 0.5]) compared to males. Social determinants like socioeconomic status (SES), crowding index or education of parents were not associated with adolescents' FI.

Conclusion: Half of the adolescents were found to be food insecure which raises concerns regarding their health in the long run. Gender is an important social determinant of FI among adolescents which suggests an in-depth exploration of social dynamics of adolescent FI. We recommend the mixed-methods study to develop contextually relevant interventions to reduce FI among this group and improve their health status.
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http://dx.doi.org/10.1186/s40795-020-00343-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098077PMC
March 2020

Investigation of an extensive outbreak of HIV infection among children in Sindh, Pakistan: protocol for a matched casecontrol study.

BMJ Open 2020 03 25;10(3):e036723. Epub 2020 Mar 25.

Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan

Introduction: In April 2019, 14 children were diagnosed with HIV infection by a private healthcare provider in Larkana district, Sindh province, Pakistan. Over the next 3 months, 930 individuals were diagnosed with HIV, >80% below 16 years, the largest ever outbreak of HIV in children in Pakistan. In this protocol paper, we describe research methods for assessing likely modes of HIV transmission in this outbreak and investigate spatial and molecular epidemiology.

Methods And Analysis: A matched case-control study will be conducted with 406 cases recruited. Cases will be children aged below 16 years registered for care at the HIV treatment centre at Shaikh Zayed Children Hospital in Larkana City. Controls will be children who are HIV-uninfected (confirmed by a rapid HIV test) matched 1:1 by age (within 1 year), sex and neighbourhood. Following written informed consent from the guardian, a structured questionnaire will be administered to collect data on sociodemographic indices and exposure to risk factors for parenteral, vertical and sexual (only among those aged above 10 years) HIV transmission. A blood sample will be collected for hepatitis B and C serology (cases and controls) and HIV lineage studies (cases only). Mothers of participants will be tested for HIV to investigate the possibility of mother-to-child transmission. Conditional logistic regression will be used to investigate the association of a priori defined risk factors with HIV infection. Phylogenetic analyses will be conducted. Global positioning system coordinates of participants' addresses will be collected to investigate concordance between the genetic and spatial epidemiology.

Ethics And Dissemination: Ethical approval was granted by the Ethics Review Committee of the Aga Khan University, Karachi. Study results will be shared with Sindh and National AIDS Control Programs, relevant governmental and non-governmental organisations, presented at national and international research conferences and published in international peer-reviewed scientific journals.
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http://dx.doi.org/10.1136/bmjopen-2019-036723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170612PMC
March 2020

Efficacy of colistin in multidrug-resistant neonatal sepsis: experience from a tertiary care center in Karachi, Pakistan.

Arch Dis Child 2020 09 20;105(9):830-836. Epub 2020 Mar 20.

Community Health Sciences, Aga Khan University, Karachi, Pakistan.

Objective: Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates.

Design/setting/patients/outcomes: We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression.

Results: 153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance.

Conclusions: Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.
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http://dx.doi.org/10.1136/archdischild-2019-318067DOI Listing
September 2020

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).

JMIR Mhealth Uhealth 2020 01 28;8(1):e12113. Epub 2020 Jan 28.

Aga Khan University, Community Health Sciences, Karachi, Pakistan.

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<125 mm Hg (18/54, 33% vs 11/52, 21%; P=.16), diastolic BP<85 mm Hg (44/54, 81% vs 37/52, 71%; P=.21), HbA level<7% (36/55, 65% vs 30/40, 75%; P=.32), and low-density lipoprotein level<100 mg/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<.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.

Trial Registration: ClinicalTrials.gov NCT02202330; https://www.clinicaltrials.gov/ct2/show/NCT02202330.
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http://dx.doi.org/10.2196/12113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013656PMC
January 2020

A multicenter case control study of association of vitamin D with breast cancer among women in Karachi, Pakistan.

PLoS One 2020 22;15(1):e0225402. Epub 2020 Jan 22.

School of Medicine, University of Adelaide, Adelaide, Australia.

Background: The prevalence of vitamin D inadequacy and breast cancer are both high among women living in Karachi, Pakistan.

Methods: A matched case control study was conducted in two hospitals of Karachi, Pakistan to evaluate the association of vitamin D (serum 25-hydroxyvitamin D) concentrations, vitamin D supplementation and sun exposure with breast cancer among Pakistani women. A total of 411 newly diagnosed histologically confirmed primary breast cancer cases were enrolled and 784 controls, free of breast and any other cancers, were matched by age (year of birth ± 5 years), residence in the same geographic area and study site. Information was collected on sociodemographic history, history of vitamin D supplementation, past medical and obstetrical history, family history of breast cancer, sun exposure history, histopathology reports and anthropometric measurement and venous blood was collected to measure serum 25-hydroxyvitamin D (25(OH)D) concentration.

Results: Compared to patients with sufficient serum vitamin D (>30 ng/ml), women with serum vitamin D deficiency (<20ng/ml), had a higher risk of breast cancer (OR = 1.65, 95%CI: 1.10, 2.50). Women with history of vitamin D supplementation one year prior to enrollment, had significant protective effect against breast cancer (OR = 0.32, 95% CI: 0.24, 0.43).

Conclusions And Recommendation: Serum vitamin D deficiency was associated with increased risk of breast cancer, while vitamin D supplementation was associated with decreased risk of breast cancer. In Pakistani women, where vitamin D deficiency is common, raising and maintaining serum vitamin D at population level is a safe and affordable strategy. It may play a role in reducing the incidence of both vitamin D deficiency and breast cancer, particularly among poor women where the breast cancer mortality is highest due to limited resources for early detection, diagnosis, and treatment. The effects of vitamin D with regard to breast cancer risk in Karachi Pakistan should be further evaluated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975526PMC
March 2020

A multicenter case control study of association of vitamin D with breast cancer among women in Karachi, Pakistan.

PLoS One 2020 22;15(1):e0225402. Epub 2020 Jan 22.

School of Medicine, University of Adelaide, Adelaide, Australia.

Background: The prevalence of vitamin D inadequacy and breast cancer are both high among women living in Karachi, Pakistan.

Methods: A matched case control study was conducted in two hospitals of Karachi, Pakistan to evaluate the association of vitamin D (serum 25-hydroxyvitamin D) concentrations, vitamin D supplementation and sun exposure with breast cancer among Pakistani women. A total of 411 newly diagnosed histologically confirmed primary breast cancer cases were enrolled and 784 controls, free of breast and any other cancers, were matched by age (year of birth ± 5 years), residence in the same geographic area and study site. Information was collected on sociodemographic history, history of vitamin D supplementation, past medical and obstetrical history, family history of breast cancer, sun exposure history, histopathology reports and anthropometric measurement and venous blood was collected to measure serum 25-hydroxyvitamin D (25(OH)D) concentration.

Results: Compared to patients with sufficient serum vitamin D (>30 ng/ml), women with serum vitamin D deficiency (<20ng/ml), had a higher risk of breast cancer (OR = 1.65, 95%CI: 1.10, 2.50). Women with history of vitamin D supplementation one year prior to enrollment, had significant protective effect against breast cancer (OR = 0.32, 95% CI: 0.24, 0.43).

Conclusions And Recommendation: Serum vitamin D deficiency was associated with increased risk of breast cancer, while vitamin D supplementation was associated with decreased risk of breast cancer. In Pakistani women, where vitamin D deficiency is common, raising and maintaining serum vitamin D at population level is a safe and affordable strategy. It may play a role in reducing the incidence of both vitamin D deficiency and breast cancer, particularly among poor women where the breast cancer mortality is highest due to limited resources for early detection, diagnosis, and treatment. The effects of vitamin D with regard to breast cancer risk in Karachi Pakistan should be further evaluated.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225402PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975526PMC
March 2020

Resilience and quality of life (QoL) of head and neck cancer and brain tumour survivors in Pakistan: an analytical cross-sectional study protocol.

BMJ Open 2019 09 20;9(9):e029084. Epub 2019 Sep 20.

Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan.

Background: Cancer is a devastating disease and has detrimental effects on the quality of life (QoL) of cancer survivors and interferes with their treatment compliance. The aim of the study is to assess resilience and QoL among cancer survivors and to evaluate the important factors affecting their resilience and QoL, with respect to the Pakistani cultural context.

Method And Analysis: A cross-sectional study will be conducted at a tertiary care hospital in Karachi, Pakistan. A minimum sample size of 250 head and neck cancers and 250 brain tumour survivors with 10% inflation for non-response rate will be required. The SD of QoL and resilience will range from 16.5 to 40.8 for head and neck cancer, and 12.7 to 34.1 for brain tumour, at 5% level of significance, with 2.5 precision. QoL will be assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-H&N35 and EORTC QLQ-BN20 and resilience will be evaluated by Wagnild and Young's 14-item scale. Mean±SD will be reported for resilience and QoL scores. Unadjusted and adjusted β-coefficients, with 95% CI, will be reported by using multiple linear regression analysis. Correlation analysis will also be performed using Pearson or Spearman rank correlation coefficients. A p value of <0.05 will be considered significant.

Ethics And Dissemination: Ethical approval has been obtained from the Aga Khan University Pakistan's Ethical Review Committee. Written informed consent will be taken from the participants by trained research assistants. A trained psychologist will provide on-spot counselling to the participants and those identified with severe depression will be referred to a psychiatrist. The study materials will be kept under lock and key and the electronic data base will be password protected and will only be accessed by the research team. The study findings will be disseminated through publications conferences and workshops and research briefs.

Trial Registration Number: Clinicaltrials.gov registry (NCT03466762).
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http://dx.doi.org/10.1136/bmjopen-2019-029084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756343PMC
September 2019

Factors associated with the discontinuation of modern methods of contraception in the low income areas of Sukh Initiative Karachi: A community-based case control study.

PLoS One 2019 3;14(7):e0218952. Epub 2019 Jul 3.

Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.

Introduction: Discontinuation of a contraceptive method soon after its initiation is becoming a public health problem in Low middle income countries and may result in unintended pregnancy and related unwanted consequences. A better understanding of factors behind discontinuation of a modern method would help in designing interventions to continue its use till desired spacing goals are achieved.

Objective: To determine factors associated with the discontinuation of modern contraceptive methods within six months of its use compared to continued use of modern method for at least six months in low-income areas of Karachi, Pakistan.

Methods: A community-based case-control study was conducted in low-income areas of Karachi. Cases were 137 users who discontinued a modern contraceptive method within 6 months of initiation and were not using any method at the time of interview, while controls were 276 continuous users of modern method for at least last six months from the time of interview. Information was collected by using a structured questionnaire. Applied logistic regression was used to identify the associated factors for discontinuation.

Results: The mean ages of discontinued and continued users were 29.3±5.3 years and 29.2±5.4 years respectively. A larger proportion of the discontinued users had no formal education (43.8%) as compared to the continued users (27.9%). The factors associated with discontinuation of a modern method of contraception were belonging to Sindhi ethnicity [OR: 2.54, 95%CI 1.16-5.57], experiencing side effects [OR: 15.12; 95% CI 7.50-30.51], difficulty in accessing contraceptives by themselves [OR: 0.40, 95%CI 0.19-0.83] and difficulty in reaching clinics for management of the side effects [OR: 4.10, 95%CI 2.38-7.05]. Moreover, women having support from the husband for contraceptive use were less likely to discontinue the method [OR: 0.58, 95% CI 0.34-0.98].

Conclusions: Sindhi ethnicity and side effects of modern methods of contraception were identified as major factors for discontinuation in low-income populations. Similarly, women who had difficulty in travelling to reach clinics for treatment also contributed to discontinuation. Furthermore, women using long acting methods and those supported by their husbands were less likely to discontinue the contraceptive methods. Findings emphasize a need to focus on Sindhi ethnicity and trainings of service providers on management of side effects and provision of high quality of services.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218952PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608957PMC
February 2020

Factors associated with geriatric morbidity and impairment in a megacity of Pakistan.

PLoS One 2019 27;14(6):e0218872. Epub 2019 Jun 27.

Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.

Background: The elderly population is increasing globally. In Pakistan, the elderly comprise 6% of the population that is predicted to triple by 2050. Non-communicable diseases are common health problems of the elderly in Pakistan, however, resulting geriatric impairments and disability are unknown. This study was conducted to determine geriatric impairments and identify associated socio-demographic factors and comorbidities among community dwelling elderly in Karachi, Pakistan.

Methods: A cross-sectional study was conducted during 2013-2014. Community clusters were selected from all sub-districts of Karachi, the largest city of Pakistan. Data was collected from systematically selected households within these clusters from individuals, aged ≥60 years, using standardized questionnaires. Geriatric impairment was assessed through validated questions and tools. We screened for depression, dementia, mobility and functional status. Descriptive statistics were computed for socio-demographic factors. We estimated the prevalence and 95% CI for geriatric impairments and comorbidities.

Results: A total of 1200 community-dwelling elderly participated in this study. More than half (n = 663, 55.3%) were females. The average age of the participants was 68.7 (SD = 7.8) years. Two-thirds suffered from chronic illness and the most common impairments were psychological and cognitive. Females were 2.45 times more at risk of developing three or more geriatric impairments. Participants with no formal education had the highest proportion (43.8%) of geriatric impairments. Participants living with more children were more likely to have three or more impairments.

Conclusion: A high burden of non-communicable diseases and associated impairments were identified among elderly in Karachi, Pakistan. High rates of psychological and cognitive impairments require urgent attention for resources and strategic planning in anticipation of a growing geriatric population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218872PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597072PMC
February 2020

Characteristics of traumatic out-of-hospital cardiac arrest patients presenting to major centers in Karachi, Pakistan-a longitudinal cohort study.

Int J Emerg Med 2018 Nov 22;11(1):50. Epub 2018 Nov 22.

Global Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.

Background: Trauma is the leading cause of death for adults under 44 years of age. Survival after traumatic out-of-hospital cardiac arrest (OHCA) has been reported to be poor, and its epidemiology is not well defined. A few studies have reported better survival in response to pre-hospital life-saving interventions. Currently, no published data on traumatic cardiac arrests in the field exist from low- and lower middle-income countries. We aimed to explore the epidemiology and outcomes of traumatic OHCA patients from Karachi, Pakistan. We conducted a longitudinal cohort study at emergency departments (ED) of five major public and private hospitals of the city from January to April 2013. Data was collected on all adult patients (age 18 years or more) presenting to the hospitals directly from field with cardiac arrest and history of trauma using a structured questionnaire. Patients with do-not-resuscitate status and those referred from other hospitals were excluded.

Results: During 3 months, a total of 187 patients were enrolled with mean age of 35.1 years. About 95% were men, and 68.4% had a penetrating injury. Even though half of the patients had a witnessed arrest, none received a bystander cardiopulmonary resuscitation (CPR). 83.4% were brought to the hospital in an ambulance, with median response and scene times of 3 and 2 min respectively; however, only 3 received any pre-hospital life-support interventions. One hundred eighty-one patients (96.7%) were pronounced dead on arrival to the ED, and of the remaining 6 patients, 4 received CPR in the EDs. Overall survival at the end of ED stay was 0%. Patients who received life-support interventions survived for longer time, though not clinically significant, as compared to those who did not (45 min vs. 35 min, p = 0.02).

Conclusion: There was no survival after a traumatic OHCA in Karachi, Pakistan. Even though ambulances reached the scene in a very short time, pre-hospital interventions were largely absent. There is a strong need to strengthen our pre-hospital care system but most importantly train the general public to deal with emergencies and be able to provide timely bystander CPR.
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http://dx.doi.org/10.1186/s12245-018-0214-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326123PMC
November 2018

LMP1 expression in bone marrow trephines of patients with multiple myeloma confers a survival advantage.

Leuk Lymphoma 2019 08 26;60(8):1991-2001. Epub 2019 Mar 26.

a Centre for Regenerative Medicine and Stem Cell Research, Aga Khan University , Karachi , Pakistan.

Multiple myeloma (MM) is a heterogeneous disease of the bone marrow (BM). Its association with Epstein-Barr virus (EBV) remains enigmatic. Aim of our study was to determine expression of latent membrane protein 1 (LMP1), aldehyde dehydrogenase 1 (ALDH1), CD117 and their association with 5-year survival in MM patients. Seven percent of cases expressed LMP1 in MM cells with no association with survival. Whereas, LMP1 expression in CD138- non-neoplastic cells was observed in 80% of the cases, conferring a survival advantage of 1.75 years (mean 3.75 ± 0.28, 95% CI 3.19-4.3). LMP1 in CD138- non-neoplastic cells was associated with CD117 expression in MM cells. Combinatorial analysis of LMP1 and CD117 stratified patients into good prognostic group LMP1+/CD117- (mean survival 4.16 ± 0.39 years) and a worst prognostic group; LMP1-/CD117+ (mean survival 1.02 ± 0.29 years). Our study showed that LMP1 expression in CD138- non-neoplastic cells of BM in MM patients confers a survival advantage.
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http://dx.doi.org/10.1080/10428194.2018.1563697DOI Listing
August 2019

Application of the GPS technology to assess time-location pattern of undergraduate students at a private medical university in Karachi, Pakistan: A pilot study.

J Pak Med Assoc 2018 Jul;68(7):1094-1096

Department of Environmental Health, Graduate School of Public Health, Seoul National University, Seoul, South Korea.

To compare time-location pattern of undergraduate university students through GPS and diary method, and with level of physical activity, a cross-sectional survey was conducted from September 2012 - May 2013 involving 50 undergraduate students from Aga Khan University. Data were recorded through GPS, diary method, International Physical Activity Questionnaire (IPAQ-L) and accelerometer (ActiGraph). Median self-reported time spent in the indoor-inside the campus, indoor-outside the campus and outdoor environment was 405 (IQR:300-540), 720 (IQR:465-840) and 300 minutes (IQR:180-495) respectively, while 52% of the students were in moderate, 40% vigorous and 8% in mild categories of physical activity. Mean differences in location (GPS versus diary method) were statistically insignificant; indoor residential, -30.2, indoor other, -26.2, outdoor at rest, 45.9 and outdoor travelling, 10.5 minutes. We conclude that students spent most of their time indoors-outside of campus and majority were physically active, while also demonstrating the applicability of GPS and ActiGraph for such studies.
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July 2018

Burden of out-of-hospital cardiac arrest in Karachi, Pakistan: Estimation through the capture-recapture method.

J Pak Med Assoc 2018 Jul;68(7):990-993

Aga Khan University Medical College, Karachi.

Objective: To assess the application of capture-recapture method as a potential strategy to estimate the incidence of out-of-hospital cardiac arrest.

Methods: This cross-sectional study was carried out from January to April 2013 in Karachi and comprised three public general hospitals, one public cardiac hospital, one private general hospital and two ambulance services. Two-sample capture-recapture method was used: first capture was through cardiac arrest data from two major emergency medical services and second capture was from the five teaching hospitals. Records from the hospitals and ambulance services were compared on 7 variables; name, age, gender, date and time of arrest, cause of arrest and destination hospital. Matched and unmatched cases were used in the equation to estimate the incidence of out-of-hospital cardiac arrest.

Results: Of the 630 out-of-hospital cardiac arrest cases reported, 191(30.3%) related to the emergency medical services records and 439(69.7%) to hospital records. The capture-recapture identified only 9(1.4%) matched cases even with the least restrictive criteria and estimated the annual out-of-hospital cardiac arrest incidence as 166/100,000 population (95% confidence interval: 142.9 to 189.6).

Conclusions: Capture-recapture method could be a potential alternative for providing population level data in the absence of organised health information systems.
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July 2018

Expression of Androgen Receptor and Cancer Stem Cell Markers (CD44/CD24 and ALDH1): Prognostic Implications in Invasive Breast Cancer.

Transl Oncol 2018 Aug 31;11(4):920-929. Epub 2018 May 31.

Center for Regenerative Medicine and Stem Cell Research; Department of Pathology and Laboratory Medicine, Aga Khan University, Stadium Road, 74800, Karachi, Pakistan. Electronic address:

Background: Androgen receptor (AR) has emerged as a significant prognostic marker in early breast cancer (BCa). Association of AR with cancer stem cell (CSC) markers in BCa is unknown. Aim of the present study was to evaluate the immunohistochemical expression of AR, CD44, CD24 and ALDH1 in a cohort of Pakistani patients diagnosed with invasive BCa and to correlate the expression with 5- year disease free survival.

Patients And Methods: We evaluated immunohistochemical expression AR, CD44, CD24 and ALDH1 in formalin fixed paraffin embedded archival blocks of 166 cases of primary invasive BCa (stage I-III) and correlated the expression with clinicopathological variables and outcome using univariable and multivariable analysis. Survival data was computed by Kaplan Meier curves.

Results: Expression of AR was observed in 62.7% tumors whereas CD44, CD24 and ALDH1 were expressed in 61.4%, 44% and 30.1% tumors, respectively. AR expression was significantly associated with T1-T2 tumors, lower grade, estrogen and progesterone receptor expression (P < .05) and remained an independent prognostic indicator in multivariable analysis (adjusted HR 0.33, 95% CI 0.13-0.81; P = .016). Significant association was observed between concordant expression of AR and CD24 (P = .001) with a favorable impact on survival (P = .007) whereas expression of CSC phenotypes (CD44, CD44/CD24 and ALDH1) did not correlate with adverse outcome (P > .05). However, AR expression retained the association with better prognosis even in patients whose tumors exhibited a CSC phenotype.

Conclusions: Expression of AR and CD24 in stage I-III invasive BCa correlates with favorable clinicopathological features and delineates a subgroup of patients with better disease-free survival.
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http://dx.doi.org/10.1016/j.tranon.2018.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041567PMC
August 2018

Lack of association of statin use with vitamin D levels in a hospital based population of type 2 diabetes mellitus patients.

Pak J Med Sci 2018 Jan-Feb;34(1):204-208

Mohammad Perwaiz Iqbal, Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

Objective: To investigate the relationship of statins (drug given to reduce serum levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes mellitus (DM) patients in a hospital in Karachi.

Methods: In a cross-sectional survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22-70 years) were recruited with informed consent. A questionnaire was administered to find out whether they were statin users or non-users. Serum was analyzed for concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and calcium using kit methods. Multiple Linear Regression was used to evaluate association of statin use with serum levels of vitamin D while adjusting for related covariates including duration of statin use, duration of type 2 DM and smoking.

Results: Mean concentrations of serum cholesterol, and LDL-cholesterol were lower among statin users compared to statin non-users ( < 0.01), while HDL-cholesterol levels were higher (<0.01). No relationship was observed between statin use and serum levels of vitamin D (=0.768), when adjusted for age, gender, BMI, duration of type 2 DM, smoking, serum cholesterol and LDL-cholesterol. The adjusted regression coefficient (β) and standard error [SE(β)] for statin use duration were 0.012 (0.042), when serum levels of vitamin D was taken as an outcome.

Conclusion: Lack of association was found between statin use and vitamin D levels in a hospital-based population of Pakistani patients with type 2 DM.
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http://dx.doi.org/10.12669/pjms.341.11977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857014PMC
April 2018

Frequency and Factors Associated with Adult Immunization in Patients Visiting Family Medicine Clinics at a Tertiary Care Hospital, Karachi.

Cureus 2018 Jan 17;10(1):e2083. Epub 2018 Jan 17.

Family Medicine, The Aga Khan University.

Objective The goal of this study was to determine the frequency and factors associated with adult immunization in patients visiting family medicine clinics at a tertiary care hospital in Karachi. Methods A cross-sectional study was conducted from March 2014 to March 2015 in a tertiary care hospital in Karachi, Pakistan. Participants more than 18 years were invited to participate in the study. A pretested questionnaire was used to collect information. Data were entered and analyzed using IBM SPSS Statistics for Windows, version 19.0 (Armonk, NY: IBM Corp). Results A total of 340 patients were surveyed. The majority of patients were female (69.5%) with a mean age of 35.47 years. The majority were married (61.1%), and 30% of the participants had completed graduation or postgraduate education (20%). Most of the patients believed that vaccines can be used in adults to prevent disease (62.2%). Patients believed that the hepatitis B vaccine, influenza vaccine, and hepatitis A vaccine can be administered to adults (58.1%, 29.9%, 33.8%, respectively). The major sources of their information regarding vaccination in adults were friends or relatives (25%) and media (23.2%). Regarding availability of vaccines, 71.3% thought a hepatitis B vaccine is available, 54.9% thought a tuberculosis vaccine is available, and 49.3% thought a tetanus toxoid vaccine is available. Only 36.4% respondents received any vaccine in adulthood. The majority of patients (62.2%) received the hepatitis B vaccine in adulthood. The major reason given for not receiving vaccines was lack of awareness (62.4%). Conclusion Low adult vaccination coverage rates and awareness, as highlighted by the results of this study, show the dire need to address this major preventive strategy. This information can be utilized to conduct larger community-based surveys, to conduct health awareness sessions in the community, and to educate our doctors regarding the availability and benefits of adult vaccines.
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http://dx.doi.org/10.7759/cureus.2083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856407PMC
January 2018

Association of Vitamin D binding protein polymorphism with risk of type 2 diabetes mellitus in a Pakistani urban population: A case control study.

J Pak Med Assoc 2017 Nov;67(11):1658-1663

Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

Objective: To assess if genotypes/diplotypes of vitamin D binding protein have any association with type 2 diabetes mellitus.

Methods: This case-control study was conducted from January 2013 to July 2015 at the endocrinology clinics of the Aga Khan University Hospital, Karachi, and comprised adult patients with type 2 diabetes and their age- and gender-matched healthy controls. Venous blood was obtained and assessed for serum/plasma 25 hydroxyvitamin D, parathyroid hormone, calcium, alkaline phosphatase and creatinine. Deoxyribonucleic acid was isolated and genotyping was done by polymerase chain reaction-restriction fragment length polymorphism procedures.

Results: Of the 330 participants, there were 165(50%) cases and as many controls. There were 116(70.3%) males and 49(29.7%) females in each group. The mean age of the patients was 48.82±9.23 years and that of the controls was 46.27±8.77 years (range: 22-70 years) (p=0.010) Mean serum concentration of 25 hydroxy vitamin D was significantly higher among the patients compared to the controls (p<0.001), but not significantly different by genotypes or diplotypes (p>0.05). Multiple conditional logistic regression revealed an association of group-specific 1-2 genotype with patients when adjusted for age, body mass index, and serum levels of 25 hydroxy vitamin D with matched adjusted odds ratio (95% confidence interval) being 3.1(1.22-7.88).

Conclusions: Group-specific 1-2 genotype of vitamin D binding protein gene was associated with the risk of type 2 diabetes.
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November 2017
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