Publications by authors named "Zeeshan Qadri"

15 Publications

  • Page 1 of 1

Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up.

Cancers (Basel) 2020 Dec 3;12(12). Epub 2020 Dec 3.

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia.

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.
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http://dx.doi.org/10.3390/cancers12123624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761718PMC
December 2020

Clonal Evolution and Timing of Metastatic Colorectal Cancer.

Cancers (Basel) 2020 Oct 12;12(10). Epub 2020 Oct 12.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours ( = 92 tumour regions) and metastases ( = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
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http://dx.doi.org/10.3390/cancers12102938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601934PMC
October 2020

Genetic heterogeneity and evolutionary history of high-grade ovarian carcinoma and matched distant metastases.

Br J Cancer 2020 04 26;122(8):1219-1230. Epub 2020 Feb 26.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Background: High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma, associated with poor clinical outcome and metastatic disease. Although metastatic processes are becoming more understandable, the genomic landscape and metastatic progression in HGSOC has not been elucidated.

Methods: Multi-region whole-exome sequencing was performed on HGSOC primary tumours and their metastases (n = 33 tumour regions) from six patients. The resulting somatic variants were analysed to delineate tumour evolution and metastatic dissemination, and to compare the repertoire of events between primary HGSOC and metastasis.

Results: All cases presented branching evolution patterns in primary HGSOC, with three cases further showing parallel evolution in which different mutations on separate branches of a phylogenetic tree converge on the same gene. Furthermore, linear metastatic progression was observed in 67% of cases with late dissemination, in which the metastatic tumour mostly acquires the same mutational process active in primary tumour, and parallel metastatic progression, with early dissemination in the remaining 33.3% of cases. Metastatic-specific SNVs were further confirmed as late dissemination events. We also found the involvement of metastatic-specific driver events in the Wnt/β-catenin pathway, and identified potential clinically actionable events in individual patients of the metastatic HGSOC cohort.

Conclusions: This study provides deeper insights into clonal evolution and mutational processes that can pave the way to new therapeutic targets.
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http://dx.doi.org/10.1038/s41416-020-0763-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156387PMC
April 2020

Evolution and Impact of Subclonal Mutations in Papillary Thyroid Cancer.

Am J Hum Genet 2019 11 24;105(5):959-973. Epub 2019 Oct 24.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia. Electronic address:

Unlike many cancers, the pattern of tumor evolution in papillary thyroid cancer (PTC) and its potential role in relapse have not been elucidated. In this study, multi-region whole-exome sequencing (WES) was performed on early-stage PTC tumors (n = 257 tumor regions) from 79 individuals, including 17 who had developed relapse, to understand the temporal and spatial framework within which subclonal mutations catalyze tumor evolution and its potential clinical relevance. Paired primary-relapse tumor tissues were also available for a subset of individuals. The resulting catalog of variants was analyzed to explore evolutionary histories, define clonal and subclonal events, and assess the relationship between intra-tumor heterogeneity and relapse-free survival. The multi-region WES approach was key in correctly classifying subclonal mutations, 40% of which would have otherwise been erroneously considered clonal. We observed both linear and branching evolution patterns in our PTC cohort. A higher burden of subclonal mutations was significantly associated with increased risk of relapse. We conclude that relapse in PTC, while generally rare, does not follow a predictable evolutionary path and that subclonal mutation burden may serve as a prognostic factor. Larger studies utilizing multi-region sequencing in relapsed PTC case subjects with matching primary tissues are needed to confirm these observations.
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http://dx.doi.org/10.1016/j.ajhg.2019.09.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849094PMC
November 2019

Whole-Exome Sequencing of Matched Primary and Metastatic Papillary Thyroid Cancer.

Thyroid 2020 01 4;30(1):42-56. Epub 2019 Dec 4.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Distant metastasis is a rare occurrence in thyroid cancer, and it can be associated with poor prognosis. The genomic repertoires of various solid malignancies have previously been reported but remain underexplored in metastatic papillary thyroid cancer (PTC). Furthermore, whether distant metastases harbor distinct genetic alterations beyond those observed in primary tumors is unknown. We performed whole-exome sequencing on 14 matched distant metastases, primary PTC tumors, and normal tissues. Point mutations, copy number alterations, cancer cell fractions, and mutational signatures were defined using the state-of-the-art bioinformatics methods. All likely deleterious variants were validated by orthogonal methods. Genomic differences were observed between primary and distant metastatic deposits, with a median of 62% (range 21-92%) of somatic mutations detected in metastatic tissues, but absent from the corresponding primary tumor sample. Mutations in known driver genes including , , and were shared and preferentially clonal in both sites. However, likely deleterious variants affecting DNA methylation and transcriptional repression signaling genes including , , and were found to be restricted in the metastatic lesions. Moreover, a mutational signature shift was observed between the mutations that are specific or enriched in the metastatic and primary lesions. Primary PTC and distant metastases differ in their range of somatic alterations. Genomic analysis of distant metastases provides an opportunity to identify potentially clinically informative alterations not detected in primary tumors, which might influence decisions for personalized therapy in PTC patients with distant metastasis.
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http://dx.doi.org/10.1089/thy.2019.0052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983753PMC
January 2020

FoxM1 is an independent poor prognostic marker and therapeutic target for advanced Middle Eastern breast cancer.

Oncotarget 2018 Apr 3;9(25):17466-17482. Epub 2018 Apr 3.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Breast cancer (BC) is the most common cause of cancer-related death in females in Saudi Arabia. BC in Saudi women tend to behave more aggressively than breast cancer in the West. Therefore, identification of new molecular targets and treatment strategies are highly warranted to improve patient outcome. FoxM1 has been shown to play a critical role in pathogenesis of various malignancies. In this study, we explored the prevalence and clinical implication of FoxM1 overexpression in Saudi breast cancer. FoxM1 protein overexpression was seen in 79% (770/975) of BC tissues and was associated with aggressive clinical parameters such as younger age (< 30 yrs) ( = 0.0172), high grade ( < 0.0001), mucinous histology ( < 0.0001) and triple negative phenotype ( < 0.0001). Overexpression of FoxM1 was significantly associated with activated AKT ( < 0.0001), Ki67 expression ( < 0.0001), VEGF ( < 0.0001), MMP-9 ( < 0.0001), XIAP ( < 0.0001) and Bcl-xL ( = 0.0300). Importantly, FoxM1 overexpression is found to be an independent prognostic marker in multivariate analysis in advanced stage (Stage III and IV) breast cancer ( = 0.0298). data using BC cell lines showed that down-regulation of FoxM1 using specific inhibitor, thiostrepton or siRNA inhibited cell migration, invasion and angiogenesis. In addition, treatment of BC cell lines with thiostrepton resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. , thiostrepton treatment regressed MDA-MB-231 cells generated xenografts via down-regulation of FoxM1 and its downstream targets. Our results suggest that FoxM1 may be a potential therapeutic target for the treatment of aggressive breast cancers.
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http://dx.doi.org/10.18632/oncotarget.24739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915129PMC
April 2018

XIAP over-expression is an independent poor prognostic marker in Middle Eastern breast cancer and can be targeted to induce efficient apoptosis.

BMC Cancer 2017 Sep 11;17(1):640. Epub 2017 Sep 11.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Cancer, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Background: Breast cancer is the most common cancer in females and is ranked second in cancer-related deaths all over the world in women. Despite improvement in diagnosis, the survival rate of this disease has still not improved. X-linked Inhibitor of Apoptosis (XIAP) has been shown to be over-expressed in various cancers leading to poor overall survival. However, the role of XIAP in breast cancer from Middle Eastern region has not been fully explored.

Methods: We examined the expression of XIAP in more than 1000 Middle Eastern breast cancer cases by immunohistochemistry. Apoptosis was measured by flow cytometry. Protein expression was determined by western blotting. Finally, in vivo studies were performed on nude mice following xenografting and treatment with inhibitors.

Results: XIAP was found to be over-expressed in 29.5% of cases and directly associated with clinical parameters such as tumor size, extra nodal extension, triple negative breast cancer and poorly differentiated breast cancer subtype. In addition, XIAP over-expression was also significantly associated with PI3-kinase pathway protein; p-AKT, proliferative marker; Ki-67 and anti-apoptotic marker; PARP. XIAP over-expression in our cohort of breast cancer was an independent poor prognostic marker in multivariate analysis. Next, we investigated inhibition of XIAP using a specific inhibitor; embelin and found that embelin treatment led to inhibition of cell viability and induction of apoptosis in breast cancer cells. Finally, breast cancer cells treated with combination of embelin and PI3-kinase inhibitor; LY294002 synergistically induced apoptosis and caused tumor growth regression in vivo.

Conclusion: These data suggest that XIAP may be playing an important role in the pathogenesis of breast cancer and can be therapeutically targeted either alone or in combination with PI3-kinase inhibition to induce efficient apoptosis in breast cancer cells.
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http://dx.doi.org/10.1186/s12885-017-3627-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594504PMC
September 2017

Molecular markers and pathway analysis of colorectal carcinoma in the Middle East.

Cancer 2015 Nov 28;121(21):3799-808. Epub 2015 Jul 28.

Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Background: Colorectal cancer (CRC) is one of the most common cancers in the world. A newly proposed integrated pathway comprising traditional, alternate, and serrated pathways by genetic and epigenetic factors was defined recently and hypothesized to play a role in the pathogenesis of CRC; however, to the authors' knowledge, there is a paucity of information regarding these proposed molecular pathways in different ethnic groups.

Methods: Molecular characterization of 770 CRC specimens was performed for microsatellite instability, BRAF, and KRAS by polymerase chain reaction and 500 cases for CpG island methylator phenotype (CIMP) high phenotype by MethyLight technology. Tumors were assigned to different molecular pathways and examined for clinicopathological correlation and survival analysis.

Results: The traditional pathway constituted 33.4% of CRC cases, the alternate pathway comprised 11.6%, and the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC cases. Approximately 54.2% of CRC cases did not qualify to fit into any pathway and thus were designated as an unassigned group. Molecular pathways were found to be significantly associated with tumor site and grade. A subset of cases with an uncategorized pathway demonstrated a significant survival difference (P = .0079).

Conclusions: The serrated pathway was found to account for a very low percentage of the CRC patient cohort in the current study. The unassigned group accounted for the majority of Middle Eastern CRC cases, and therefore methods of CRC pathway analysis might not be applicable to this ethnic group. The current study demonstrates the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies a need for further studies on different populations for a better understanding of their exact role and incidence.
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http://dx.doi.org/10.1002/cncr.29580DOI Listing
November 2015

The biological and clinical impact of inhibition of NF-κB-initiated apoptosis in diffuse large B cell lymphoma (DLBCL).

J Pathol 2011 Jul 19;224(3):355-66. Epub 2011 Apr 19.

Human Cancer Genomic Research, Research Center, King Fahad National Center for Children's Cancer, Riyadh, Saudi Arabia.

NF-κB is frequently over-expressed in a variety of non-Hodgkin's lymphomas (NHLs) and has been implicated in lymphomagenesis; however, its role in diffuse large B cell lymphoma (DLBCL) as a prognostic biomarker has not been fully elucidated. Therefore, we investigated the role of NF-κB and its association with clinicopathological features in a tissue microarray cohort of 230 DLBCL patient samples. We then elucidated the role of NF-κB inhibition on cell viability and apoptosis in vitro, using DLBCL cell lines. Using immunohistochemistry, NF-κB was detected in 25.6% (52/203) DLBCL tumours, was associated with activated B cell (ABC) phenotype (p = 0.0054), Epstein-Barr virus (EBV; p = 0.0080) and over-expression of the anti-apoptotic marker XIAP (p = 0.0013). DLBCL cases with nuclear expression of NF-κB showed a significantly poorer overall survival as compared to those without NF-κB expression (p = 0.0236). In a multivariate analysis using a Cox proportional hazard model for IPI and NF-κB expression, the relative risk was 2.97 for high NF-κB expression (95% CI 1.27-6.94; p = 0.0113) and 7.55 for the high-IPI group (95% CI 3.34-18.35; p < 0.0001). In vitro, Bay 11-7085 inhibited constitutively active NF-κB expression in a dose-dependent manner and inhibition of NF-κB also down-regulated expression of the downstream target gene products Bcl-2, Bcl-XL (BCL2L1), XIAP and Survivin, leading to apoptosis via activation of the mitochondrial apoptotic pathway. NF-κB over-expression was found to be an independent prognostic marker for poor survival in DLBCL. Altogether, these results suggest that NF-κB may be a useful prognostic biomarker and a potential target for therapeutic intervention in DLBCL.
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http://dx.doi.org/10.1002/path.2864DOI Listing
July 2011

Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations.

Mol Cancer 2010 Jul 30;9:203. Epub 2010 Jul 30.

Department of Human Cancer Genomic Research, MBC 98-16,Research Centre at KFNCCC, King Faisal Specialist Hospital and Research Centre,PO Box 3354, Riyadh 11211,Kingdom of Saudi Arabia.

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells.

Methods: We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival.

Results: CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251) and a histology subtype of adenocarcinomas (p = 0.0355). Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p < 0.0001), histology subtype of adenocarcinomas (p = 0.0010) and tumors in left colon (p = 0.0009). Over expression of pro apoptotic markers: p27KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011). Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L) phenotype (p = 0.0003) and with absence of KRAS mutations (p = 0.0481).

Conclusion: TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.
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http://dx.doi.org/10.1186/1476-4598-9-203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922191PMC
July 2010

A multicentre matched case control study of risk factors for preeclampsia in healthy women in Pakistan.

BMC Womens Health 2010 Apr 30;10:14. Epub 2010 Apr 30.

Division of Epidemiology/Biostatistics, Department of Community Health Sciences, Aga Khan University, Karachi, Pakistan.

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and mortality world-wide. The risk for developing preeclampsia varies depending on the underlying mechanism. Because the disorder is heterogeneous, the pathogenesis can differ in women with various risk factors. Understanding these mechanisms of disease responsible for preeclampsia as well as risk assessment is still a major challenge. The aim of this study was to determine the risk factors associated with preeclampsia, in healthy women in maternity hospitals of Karachi and Rawalpindi.

Methods: We conducted a hospital based matched case-control study to assess the factors associated with preeclampsia in Karachi and Rawalpindi, from January 2006 to December 2007. 131 hospital-reported cases of PE and 262 controls without history of preeclampsia were enrolled within 3 days of delivery. Cases and controls were matched on the hospital, day of delivery and parity. Potential risk factors for preeclampsia were ascertained during in-person postpartum interviews using a structured questionnaire and by medical record abstraction. Conditional logistic regression was used to estimate matched odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: In multivariate analysis, women having a family history of hypertension (adjusted OR 2.06, 95% CI; 1.27-3.35), gestational diabetes (adjusted OR 6.57, 95% CI; 1.94 -22.25), pre-gestational diabetes (adjusted OR 7.36, 95% CI; 1.37-33.66) and mental stress during pregnancy (adjusted OR 1.32; 95% CI; 1.19-1.46, for each 5 unit increase in Perceived stress scale score) were at increased risk of preeclampsia. However, high body mass index, maternal age, urinary tract infection, use of condoms prior to index pregnancy and sociodemographic factors were not associated with higher risk of having preeclampsia.

Conclusions: Development of preeclampsia was associated with gestational diabetes, pregestational diabetes, family history of hypertension and mental stress during pregnancy. These factors can be used as a screening tool for preeclampsia prediction. Identification of the above mentioned predictors would enhance the ability to diagnose and monitor women likely to develop preeclampsia before the onset of disease for timely interventions and better maternal and fetal outcomes.
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http://dx.doi.org/10.1186/1472-6874-10-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881882PMC
April 2010

Community-based interventions to promote blood pressure control in a developing country: a cluster randomized trial.

Ann Intern Med 2009 Nov;151(9):593-601

Aga Khan University, Karachi, Pakistan.

Background: Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries.

Objective: To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults.

Design: Cluster randomized, 2 x 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574)

Setting: 12 randomly selected communities in Karachi, Pakistan.

Patients: 1341 patients 40 years or older with hypertension (systolic blood pressure >or=140 mm Hg, diastolic blood pressure >or=90 mm Hg, or already receiving treatment).

Measurements: Reduction in systolic blood pressure from baseline to end of follow-up at 2 years.

Intervention: Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management.

Results: The age, sex, and baseline blood pressure-adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis).

Limitations: Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure.

Conclusion: Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries.

Primary Funding Source: Wellcome Trust.
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http://dx.doi.org/10.7326/0003-4819-151-9-200911030-00004DOI Listing
November 2009

Prevalence of microalbuminuria and associated electrocardiographic abnormalities in an Indo-Asian population.

Nephrol Dial Transplant 2009 Jul 18;24(7):2111-6. Epub 2009 Feb 18.

Section of Nephrology, Department of Medicine, Aga Khan University, Karachi, Pakistan.

Background: Microalbuminuria (MA) is a known predictor of cardiovascular disease (CVD) in European origin populations, but such data are lacking in native Indo-Asian populations, where CVD risks are high. Major electrocardiographic (ECG) changes are predictive of cardiovascular mortality. We determined the association of MA with major ECG changes in the general population of Pakistan.

Methods: A total of 3143 subjects aged >or=40 years from 12 randomly selected communities in Karachi participated. MA was defined as the urine albumin to creatinine (ACR) ratio of < 300 mg/g creatinine and >or=17 mg/g in men and >or=25 mg/g in women from a single-spot morning urine sample. Major changes on ECG were coded in duplicate using Minnesota classification.

Results: The mean age of subjects was 51.5 (10.7) years. The median (25-75 percentile) ACR was 4.2 (2.9-7.9) mg/g in men and 6.0 (3.9-10.8) mg/g in women (P < 0.001). The overall prevalence (95% CI) of MA was 12.3% (11.1-13.5%), and 20.3% in those with major ECG changes. In a multivariable model, major ECG changes (OR, 95% CI) (1.50, 1.10-2.00), diabetes (3.57, 2.93-4.35), hypertension (2.30, 1.85-2.86), female sex (0.61, 0.53-0.69), age (1.09, 1.05-1.13, for each 5-year increase) and eGFR (0.80, 0.78-0.81, for each 10 mg/g increase) were independently associated with MA. The presence of MA increased the prevalence of major ECG changes from 21 to 31% in those with hypertension (44.9%), 15 to 28% among those with diabetes (21.4%), 14 to 26% among those with overweight or obesity (68.4%) and 14 to 26% among current users of tobacco (38.7%) (P < 0.001) each.

Conclusions: The strong association between MA and major ECG changes underscores the importance of screening Indo-Asian subjects for MA for unmasking underlying CVD, especially those with hypertension, diabetes, obesity, and tobacco users.
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http://dx.doi.org/10.1093/ndt/gfp042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698093PMC
July 2009

Secondary prevention of heart disease--knowledge among cardiologists and omega-3 (omega-3) fatty acid prescribing behaviors in Karachi, Pakistan.

BMC Cardiovasc Disord 2009 Jan 27;9. Epub 2009 Jan 27.

Section of Cardiology, Department of Medicine, Aga Khan University, Aga Khan, Pakistan.

Background: The use of omega-3 fatty acids is a currently proven strategy for secondary prevention of heart disease. The prescription practices for this important nutraceutical is not currently known. It is imperative to assess the knowledge of cardiologists regarding the benefits of omega-3 fatty acids and to determine the frequency of its prescription. The aim of the study was to determine the practices and associations of dietary fish prescribing among cardiologists of Karachi and to assess their knowledge of fish oil supplementation and attitudes toward dietary practices.

Methods: A cross sectional survey was conducted during the period of January to March, 2008. A self report questionnaire was employed. All practicing cardiologists of Karachi were included in the study. Multiple logistic regression analysis was performed to determine the independent factors associated with high fish prescribers.

Results: The sample comprised of a total of 163 cardiologists practicing in Karachi, Pakistan. Most (73.6%) of the cardiologists fell in the age range of 28-45 years and were male (90.8%). High fish prescribers only comprised 36.2% of the respondents. After adjusting for age and gender, multivariate analysis revealed that only the variable of knowledge about fish oil's role in reducing sudden cardiac death was independently associated with high fish prescribers OR = 6.38 [95% CI 2.58-15.78].

Conclusion: The level of knowledge about the benefits of omega-3 fatty acids is high and the cardiologists harbor a favorable attitude towards dispensing dietary fish advice. However, the prescription practices are less than optimal and not concordant with recommendations of organisations such as the American Heart Association and National Heart Foundation of Australia. The knowledge of prevention of sudden cardiac death in CVD patients has been identified as an important predictor of high fish prescription. This particular life-saving property of omega-3 fatty acids should be the focus of any implemented educational strategy targeted to improve secondary CVD prevention via omega-3 fatty acid supplementation.
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http://dx.doi.org/10.1186/1471-2261-9-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2640345PMC
January 2009

Depression in the elderly: does family system play a role? A cross-sectional study.

BMC Psychiatry 2007 Oct 25;7:57. Epub 2007 Oct 25.

Medical College, The Aga Khan University, Karachi, Pakistan.

Background: The most common geriatric psychiatric disorder is depression. The role of family systems in depression among the elderly has not been studied extensively. It has been suggested that urbanization promotes nucleation of family systems and a decrease in care and support for the elderly. We conducted this study in Karachi, a large urban city of Pakistan, to determine the relationship between the type of family system and depression. We also determined the prevalence of depression in the elderly, as well as correlation of depression with other important socio-demographic variables.

Methods: A cross-sectional study was carried out in the premises of a tertiary care hospital in Karachi, Pakistan. Questionnaire based interviews were conducted among the elderly people visiting the hospital. Depression was assessed using the 15-item Geriatric Depression Scale.

Results: Four hundred subjects aged 65 and above were interviewed. The age of majority of the subjects ranged from 65 to 74 years. Seventy eight percent of the subjects were male. The prevalence of depression was found to be 19.8%. Multiple logistic regression analysis revealed that the following were significant (p < 0.05) independent predictors of depression: nuclear family system, female sex, being single or divorced/widowed, unemployment and having a low level of education. The elderly living in a nuclear family system were 4.3 times more likely to suffer from depression than those living in a joint family system (AOR = 4.3 [95% CI = 2.4-7.6]).

Conclusion: The present study found that residing in a nuclear family system is a strong independent predictor of depression in the elderly. The prevalence of depression in the elderly population in our study was moderately high and a cause of concern. The transition in family systems towards nucleation may have a major deleterious effect on the physical and mental health of the elderly.
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http://dx.doi.org/10.1186/1471-244X-7-57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194680PMC
October 2007