Patients In Pakistan Research Articles

Epidemiology of glioblastoma in Pakistan: a secondary analysis of the Pakistan Brain Tumor Epidemiology Study (PBTES).

The incidence and outcomes of glioblastoma (GBM) patients in Pakistan remain unassessed owing to a lack of cancer registries and the absence of population-based studies. For any specific population-based oncological intervention, epidemiology must be studied. Therefore, this study aims to examine the epidemiological characteristics of glioblastoma patients in Pakistan, as part of a secondary analysis of a nationwide epidemiological study. Data comprising of sociodemographic, tumor and treatment characteristics of 2750 patients from the Pakistan Brain Tumor Epidemiology Study were extracted and analyzed for cases between January 1, 2019, and December 31, 2019. Chi-square tests identified outcome and treatment differences. Data analysis was performed using SPSS version 26. A total of 260 GBM cases were analyzed, with a mean diagnosis age of 45 years. Males accounted for 68.8%. Most patients were from a middle- (39.6%) or lower-income (42.7%) socioeconomic background and received care from a public institution (63.8%). GBM tumors were mainly located in the frontal lobe with similar proportions of right and left laterality. A median distance of 119km was traveled for oncological care, and the mean time to surgery from the initial radiological diagnosis was 72 days. Gross total resection was achieved in 47.3% of first surgeries, with 23 reoperations for recurrence. At the end of the study period, 33% of the GBM cohort was recorded as alive with 47% being lost to follow-up. Our analysis is the first population-based analysis of GBM in Pakistan. This epidemiologic study can serve as a basis for future research in etiology, treatment, and outcomes for glioblastoma in the Pakistani population.

CFTR Exon 10 deleterious mutations in patients with congenital bilateral absence of vas deferens in a cohort of Pakistani patients.

Congenital bilateral absence of vas deferens (CBAVD) is a urological syndrome of Wolffian ducts and is responsible for male infertility and obstructive azoospermia. This study is designed to explore the integrity of exon 10 of CFTR and its role in male infertility in a cohort of CBVAD patients in Pakistan. Genomic DNA was extracted from 17 male patients with CBAVD having clinical symptoms, and 10 healthy controls via phenol-chloroform method. Exon 10 of the CFTR gene was amplified, using PCR with specific primers and DNA screening was done by Sanger sequencing. Sequencing results were analyzed using freeware Serial Cloner, SnapGene, BioEdit and FinchTV. Furthermore, bioinformatics tools were used to analyze the mutations and their impact on the protein function and stability. We have identified 4 mutations on exon 10 of CFTR in 6 out of 17 patients. Two of the mutations were missense variants V456A, K464E, and the other two were silent mutations G437G, S431S. The identified variant V456A was present in 4 of the studied patients. Whereas, the presence of K464E in our patients further weighs on the crucial importance for its strategic location to influence the gene function at post-transcriptional and protein level. Furthermore, Polyphen-2 and SIFT analyze the mutations as harmful and deleterious. The recurrence of V456A and tactically conserved locality of K464E are evidence of their potential role in CBAVD patients and in male infertility. The data can contribute in developing genetic testing and treatment of CBAVD.

Abstract B010: Design of personalized neoantigen mRNA vaccines against breast cancer patients in Pakistan based on next-generation sequencing data

Abstract Breast cancer is the most common malignancy among women in Pakistan, with an outrageous increase in the incidence and mortality rate. Because of decreased effectiveness and lower survival rates, there is an urgent need for developing novel, personalized vaccines with enhanced activity. The development of a personalized mRNA vaccine illustrates a promising approach to combating the prevalence of breast cancer. We used the whole exome sequencing (WES) data of Pakistani tumor samples to predict immunogenic neoantigens. The WES data was aligned to the GRCM39 reference genome using BWA. The genome analysis toolkit (GATK) was employed for variant calling to identify somatic mutations. Using immune-bioinformatics tools, we predicted cytotoxic CD8+ T cell epitopes and helper CD4+ T cell epitopes within the identified neoantigens and designed vaccines by assembling the fusion of CTL neoepitopes, helper sequences, and adjuvants together with linkers. The Insilco ImmSim algorithm was used to examine the immune responses of the vaccine. The vaccine design was further explored by checking its simulation effect on the immune system, its physiochemical characteristics, its binding to specific immune system molecules, and cloning into an appropriate vector. In addition, molecular docking, MD simulation, and binding free energies were performed to investigate the interaction mechanism between the construct vaccine and Toll-like receptors (TLR2, TLR4, TLR7, and TLR9).By examining these factors, we aimed to ensure the vaccine's safety, stability, and ability to bind tightly to specific immune cells (class I MHC molecules), ultimately triggering a comprehensive immune response against breast cancer cells. Citation Format: Kayode Yomi Raheem, Muhammad Muddassar. Design of personalized neoantigen mRNA vaccines against breast cancer patients in Pakistan based on next-generation sequencing data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B010.

A Survey of Acute Transfusion Reactions in Thalassemic Patients in Pakistan: A Single Centre Experience

Background: Blood transfusion reactions are characterized as adverse reactions linked to whole blood or any of its constituent parts, encompassing a spectrum of severity levels, from minor to potentially life-threatening. The administration of blood products is a common practice to enhance the hemodynamic status and overall clinical well-being of patients. However, it's important to note that transfusing blood components comes with potential complications, both infectious and non-infectious in nature. Objective: The current study aim to evaluate the type and frequency of transfusion reactions in thalassemic patients at Hamza Foundation Welfare Hospital and Blood Services, Peshawar. Method: The current study was a descriptive cross-sectional study. The data was collected from 152 participants through a self-generated questionnaire during the 4 months (from April to July 2022) study period. Results: The overall frequency of febrile non-hemolytic reactions (FNHTR), allergic transfusion reactions (ATR), and acute hemolytic transfusion reactions (AHTR) was 84%. Among the 152 participants, 91 (59.8%) were males, and 61 (40.2%) were females. Of the total males, 83 (55.6%) experienced transfusion reactions, while 46 (30%) of the females had transfusion reactions. Specifically, 56 males and 36 females experienced FNHTRs, 22 males and 4 females experienced ATRs, and 5 males and 6 females experienced AHTRs. Fever was observed predominant symptom 69.7% and 52.6% among FNHTR and AHTR, anxiety was predominantly observed in 34.8% in ATRs. Conclusion: Among the transfusion reaction types, FNHTRs emerged as the most common, followed by ATRs and AHTRs. Key words: Febrile Non-Hemolytic Reaction, Allergic Transfusion Reaction, Hemolytic Transfusion Reactions

BRAF mutations and the association of V600E with CD133 and CDX2 expression in a Pakistani colorectal carcinoma cohort

BackgroundDespite a high incidence of colorectal carcinoma, data regarding genetic aberrations in colorectal carcinoma (CRC) patients in Pakistan is scarce. This study aimed to determine the frequency of BRAFV600E mutations in colorectal carcinoma tissue in the Pakistani population and to associate BRAFV600E expression with CD133, a marker of colorectal stem cells, and CDX2 marker of differentiation.MethodsSanger Sequencing of exon 15 (426 bp) including the hotspot V600E was performed on formalin-fixed-paraffin-embedded (FFPE) CRC tissue samples of 115 patients. The samples were subjected to immunohistochemistry (IHC) to assess the expression of BRAFV600E, CDX2, and CD133. Additionally, homology modelling and docking were performed to investigate novel deletions revealed in sequencing.ResultsTwenty-four (20.8%) BRAF variants were identified in the coding region, with V600E mutations detected in 14 (12.2% )cases (GenBank: PP003258.1; Pop Set: 2678087296). Moreover, a wide spectrum of novel non-V600E mutations (8.6%) were identified, including deletions and missense variations. In-silico analysis revealed that due to large deletions in the coding region of three samples, the affinity of the anti-BRAF drugs (Encorafenib and Vemurafenib) for the active site decreased in comparison to the wild type. The IHC analysis showed that BRAFV600E expression was significantly associated with CD133 expression (χ2(1, n=115) = 26.351; p = < 0.001) and with CDX2 expression (χ2(1, n=115) = 14.88; p = 0.001). Multivariate analysis using binary logistic regression revealed association of BRAFV600E mutations with age (OR = 1.123; CI = 1.024–1.232; p = 0.014), gender (OR = 0.071; CI = 0.006–0.831; p = 0.035), grade (0.007; CI = 0-0.644) and CD133 expression (OR = 65.649; CI = 2.153-2001.556; p = 0.016).ConclusionThe present study demonstrates a notably high V600E frequency (12.2%) in comparison to global reported data, which ranges from 0.4 to 18%. This finding reflects the importance of upfront BRAF testing of the genetically distinct population of Pakistan. Previously unreported mutations identified in the sample may be of clinical significance and warrant further investigation. The concomitant high expression and significant association between CD133 and BRAFV600E represent vital actionable genes that may be targeted together to improve CRC patient management.

Occurrence and antimicrobial resistance of Campylobacter jejuni isolated from poultry and hospitalized diarrheal patients in Pakistan

The leading human enteropathogen Campylobacter jejuni (C. jejuni) is recognized as a major public-health concern, due to emerging multidrug resistant (MDR) strains, and associated post-infectious complications. Therefore, the present study determined the occurrence of C. jejuni in diarrheal cases and poultry, in Khyber Pakhtunkhwa Province, Pakistan, and associated antimicrobial resistance patterns. In total, 840 samples were collected from clinical and different poultry sources between May 2019 to April 2020, to determine the occurrence, seasonal variations, bacterial loads in diverse poultry samples, age-related variations in human infections as well as associated antimicrobial resistance patterns of C. jejuni, highlighting its “One Health significance” at the human-food interface. Clinical samples (n = 240) from five age-groups of hospitalized diarrhoea patients, showed occurrence rate of 39 %, which peaked in the summer and was highest in children under 5. In poultry samples, 57 % (342/600) were positive for C. jejuni, varied from 45 % (109/240) in chicken meat to 65 % (233/360) in farm samples. Except frozen meat, C. jejuni-positive poultry samples showed seasonal contamination levels, with summer having the highest bacterial loads. In chicken meat, 2 % of positive samples (2/109) had bacterial loads <1 logCFU/g, while 20 % (22/109) exceeding 3log CFU/g. Grocery store samples showed lower bacterial contamination. All human and poultry isolates (n = 436) were resistant to nalidixic acid (100 %) and none to amikacin (0 %). Of these, 66 % showed multidrug resistance, with 9 % (38/436) resistant to panel of seven out of eight antibiotics tested. This study highlights the high occurrence of and concerns about MDR C. jejuni in Khyber Pakhtunkhwa, Pakistan, particularly in young children.

Factors affecting the recovery of COVID-19 patients in Pakistan, with a focus on smoking: A comprehensive analysis

This research paper delves into the various factors influencing the recovery of COVID-19 patients in Pakistan, with a specific emphasis on the impact of tobacco smoking. To unravel these connections, we conducted a data collection campaign employing a custom-designed questionnaire, gathering responses from 170 individuals who had successfully recovered from the coronavirus. Subsequently, we employed the Ordinary Least Squares (OLS) method to examine the influence of socio-economic factors on the recovery process. Our findings revealed that patients within the age range of 36 to 46 years exhibited an extended recovery period, requiring an additional three days for recuperation compared to their younger counterparts aged 17 to 25 years. Furthermore, patients aged above 46 years experienced a more prolonged recovery period, with a delay of up to seven days. Residence played a pivotal role in recovery times, as urban-dwelling patients showed a noteworthy advantage, recuperating 1.5 days sooner than their rural counterparts. A conspicuous relationship emerged regarding smoking habits, as patients who smoked tobacco required an additional two days for recovery when compared to non-smokers. Similarly, patients classified as obese experienced 2.6 more days to regain their health compared to individuals with a normal Body Mass Index (BMI). Remarkably, our analysis revealed that factors such as income, gender, and education were insignificant in terms of the number of the days required for recovery. These results provide a comprehensive understanding of the dynamics at play in the recovery process of COVID-19 patients in Pakistan, offering valuable insights for healthcare professionals and policymakers.

Impact of Early Invasive Strategy on Left Ventricular Function Recovery in Acute Myocardial Infarction Patients in Pakistan.

Background Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries like Pakistan, where healthcare resources are limited. Early Invasive Strategy (EIS), typically involving percutaneous coronary intervention (PCI), has been shown to improve outcomes in AMI patients. However, the effectiveness of EIS in resource-limited settings, such as Pakistan, remains under-explored. Objective This prospective observational cohort study aimed to assess the impact of an Early Invasive Strategy (EIS) on left ventricular (LV) function recovery in acute myocardial infarction (AMI) patients in Pakistan. The primary objective was to measure the change in left ventricular ejection fraction (LVEF) over six months. Secondary objectives included evaluating mortality, rehospitalization rates, and incidences of major adverse cardiovascular events (MACE). Multivariate regression analysis was employed to adjust for potential confounders. Methods The study was conducted from January to December 2023 at the National Institute of Cardiovascular Diseases (NICVD) satellite centers in Sukkur, Nawab Shah, and Khairpur. A total of 300 AMI patients presenting within 24 hours of symptom onset were included. Participants were divided into two groups: the EIS group (n = 150) received percutaneous coronary intervention (PCI) within 24 hours of admission, while the delayed treatment group (n = 150) received standard therapy, with invasive procedures performed after 24 hours if clinically indicated. Data were collected at baseline, during hospitalization, and at three- and six-months post-AMI. Results The EIS group demonstrated a significantly greater improvement in LVEF compared to the delayed treatment group (13.1% [95% CI, 10.8%-15.4%] vs. 7.5% [95% CI, 5.8%-9.2%], p < 0.001). Mortality was lower in the EIS group (3% [n = 4] vs. 9% [n = 13], p = 0.01), as were rehospitalizations for heart failure (7% [n = 10] vs. 14% [n = 21], p = 0.02) and incidences of MACE (8% [n = 12] vs. 16% [n = 24], p = 0.01). Multivariate regression analysis confirmed that EIS was independently associated with better LVEF improvement (coefficient = 5.78 [95% CI, 4.21-7.35], p < 0.001). Conclusion Early invasive treatments significantly enhance left ventricular function recovery and reduce mortality and rehospitalization rates in AMI patients in Pakistan. These findings advocate for the implementation of timely PCI interventions in resource-limited settings to improve clinical outcomes, particularly emphasizing cost-effectiveness and the availability of PCI.

Assessment of barriers to the dietary adherence among type 2 diabetic patients in Pakistan: A cross-sectional study.

To assess the common barriers responsible for non-adherence to dietary recommendations among type 2 diabetic patients. The cross-sectional study was conducted from October 4, 2021, to March 6, 2022, at the National Institute of Diabetes and Endocrinology, Dow University of Health Sciences, Karachi, and comprised type 2 diabetes patients of either gender aged 18-80 years who had previously been given recommended dietary advice. Dietary barriers were assessed using a 27-item validated questionnaire, and the subjects were compared in terms of age and diabetes duration. Anthropometric measurements and laboratory parameters were also measured. Data were analysed using Stata 17. Of the 312 subjects, 234(75%) were females. The overall mean age was 52.2±11.2 years, and mean body mass index was 27.2±5.5kg/m2. The reliability of the questionnaire was established with Cronbach's alpha 0.89. Factor analysis yielded 8 common barriers; lack of knowledge about dietary recommendations (variance: 14.7%), situational barrier (variance: 10.7%), lack of family support (variance: 9.5%), stress-related eating problems (variance: 9.1%), boring and monotonous diet (variance: 8.0%), expensive and ineffective diet recommended (variance: 6.5%), work conditions/don't like food in diet (variance: 5.5%), and feeling hungry and weak (variance: 5.4%). The total variation explained by all the 8 factors was 69.4%. Lack of knowledge regarding dietary recommendations was reported to be the most common barrier towards recommended dietary adherence.

TB disease yield from household contact screening of TB index patients in Pakistan.

<sec><title>OBJECTIVES</title>The national guidelines recommend contact screening of a subset of patients with the TB index and their household contacts (HHCs). Thus, many contacts with TB remain unscreened.</sec><sec><title>METHODS</title>We collected prospective data under programmatic conditions in Karachi, Pakistan, from January 2018 to December 2019. We screened all HHCs of all patients using the TB index. We disaggregated the data into guideline-eligible or ineligible index patients and contacts. We calculated TB disease yields for different groups of index patients and contacts.</sec><sec><title>RESULTS</title>Of 39,168 HHCs from 6,450 index patients, 21,035 completed clinical assessments for TB, and 416 were diagnosed with all forms of TB. HHCs of patients with clinically diagnosed pulmonary TB (PTB) were as likely to be diagnosed with TB as the HHCs of patients with bacteriologically confirmed PTB (adjusted OR 1.28, 95% CI 0.94-1.75). The yield of TB disease among child contacts (3.4%) was significantly higher than that among adult contacts (0.5%) (P < 0.001).</sec><sec><title>CONCLUSIONS</title>Broadening household contact screening criteria could increase the yield of contact tracing and improve the diagnosis of TB. However, further studies are required to establish the feasibility and cost-effectiveness of this approach, including studies from more diverse settings.</sec>.

Patient-reported outcomes for immediate breast reconstruction with mastectomy among breast cancer patients in Pakistan.

To evaluate the effect of immediate breast reconstruction with mastectomy in the local population. The quasi-experimental, control study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised patient data from April 2017 to December 2020, of breast cancer patients who underwent mastectomy with or without immediate breast reconstruction. Those who underwent mastectomy were labelled as control group A, while patients with immediate breast reconstruction were labelled as intervention group B. Data was analysed using SPSS 20. Of the 66 patients, 33(50%) were in each of the 2 groups. Group B had significantly more patients aged <40 years than group A (p=0.01), more patients with graduate-level education (p=0.04), and more patients who were either unmarried or divorced (p=0.05) than group A. Group B patients had higher mean scores for satisfaction with breasts (p=0.001) and psychosocial wellbeing (p=0.001) than those in in group A. Mean scores for adverse effects of radiotherapy were significantly higher in group B than in group A (p=0.04). Better health-related outcomes were reported by patients who underwent immediate breast reconstruction with mastectomy.

HGG-28. THE IMPACT OF CMMRD IN HIGH-GRADE GLIOMA PATIENTS, A RETROSPECTIVE ANALYSIS OF 7 YEARS IN LMIC; AN IRRDC STUDY

Abstract BACKGROUND Constitutional mismatch repair (MMR) deficiency (CMMRD) is a genetic cancer predisposition syndrome presenting among children and young adults. This study is the first to evaluate CMMRD prevalence among high-grade glioma patients in Pakistan, a country with high consanguinity rates. METHODS We reviewed data of patients younger than 18 diagnosed with pediatric high-grade glioma, anaplastic astrocytoma, and diffuse midline glioma with CMMRD testing between 2016 and 2023. Tumor slides of all included cases were prepared and sent to Sick Kids Toronto to review the MMR protein stains via multi-gene panels. RESULTS Forty-five patients were identified (62.3% females); median age of 11. Headache (88.9%) was the most common symptom, followed by vomiting (60%) and seizures (37.8%); median duration of symptoms was two months. Histopathology revealed 73.3% pediatric high-grade glioma, 22.2% Anaplastic Astrocytoma, and 4.4% Diffuse Midline Glioma. Thirty-six patients (80%) had a cerebral tumor, 13.3%, and 6.7% had a posterior fossa and midline tumor, respectively. CMMRD was positive in 15 of 45 patients (33.3%). Eight patients (53.4%) had CMMRD with loss of PMS 2, two (13.3%) had loss of PMS 2 and MLH 1, two (13.3%) had loss of MSH 2, two (13.3%) had loss of MSH 6, and only one patient had loss of MSH 6 and MSH 2. Consanguinity correlated with CMMRD (P=0.045), but family history of malignancy was not significant (P=0.202). One-year overall survival of all patients, with a median follow-up of 4.8 months, was 44.4 %, whereas 1-year overall survival compared to CMMRD was 33.3%, with a median follow-up of 7.2 months (P=0.616) CONCLUSION We found high prevalence of CMMRD among pediatric high-grade glioma patients and patients with consanguinity. The findings of our study emphasize the importance of genetic testing and counseling. Timely accurate diagnosis is essential as decreased response to conventional treatment regimens may increase disease burden.

Epidemeiology of Burns in Peadiatric Patients in Pakistan: A Systemic Review

Burns are graded as the fourth most common trauma type globally followed by other traumas including accidents, interpersonal violence and falls. South Asian regions account for 187- 243 incidences of burns in adults per hundred thousand annually. Moreover, about 22.5% of all burns occur in children and youth. 42% of those in children between the ages of 5 to 16 years old. Whereas Pakistan lacks national data and cannot measure the burn burden annually. Due to the lack of clinical and epidemiological studies on burns in pediatrics patients in Pakistan, we performed this study. This systemic review study aimed at summarizing available Pakistan’s epidemiological data, based on national studies in the past 32 years. The data of our systemic review were collected from six search engines, i.e. PubMed, Google Scholar, PakMediNet, Scopus, Springer and DOAJ. The studies which were reviewed for the article were from 1990 to 2022. The articles of nonhuman participants, duplication and lacking in primary focus were excluded. The PRISMA guidelines were used. A total of 11 articles were included out of which 4 are from Islamabad ICT, 2 from Sindh, 1 from Balochistan and 4 from Punjab. The overall gender ratio shows male dominance of 55.83 %. Scald burn were recorded at a higher percentage of 48.7%. The mean TBSA recorded in this research was 17%. The mean mortality rate of all the studies shows a percentage of 14.84%. More research studies are needed to be done in the areas lacking information about the victims of burn injuries so that policymakers know the actual figure of the injuries with whom they have to deal.

EFFICACY OF INTRAPLEURAL STREPTOKINASE IN RETAINED HEMOTHORAX

Retained hemothorax is a challenging clinical entity characterised by the accumulation of blood within the pleural cavity following chest trauma or surgery. In recent years, intrapleural streptokinase has emerged as a potential therapeutic option for managing retained hemothorax, offering a less invasive alternative to surgical interventions. However, limited data are available on the efficacy of this treatment modality in the Pakistani population. Objective: This study aimed to evaluate the effectiveness and safety of intrapleural streptokinase in resolving retained hemothorax among patients in Pakistan. Methods: A prospective observational study was conducted at a Rawalpindi Teaching Hospital in Pakistan from January 2022 to July 2023. One hundred patients meeting the inclusion criteria were enrolled in the study. Baseline demographic and clinical data were recorded, and intrapleural streptokinase therapy was administered according to standard protocols. Response to treatment was assessed through regular clinical examinations and radiological imaging over a predetermined duration. Descriptive statistics were used to summarise baseline characteristics, and inferential statistics, such as chi-square tests or t-tests, were utilised to compare outcomes between subgroups. Results: Of the 100 patients treated with intrapleural streptokinase therapy, 85% achieved successful resolution of retained hemothorax, as evidenced by complete drainage of blood from the pleural cavity and radiological confirmation of lung re-expansion. A subset of patients who did not respond to therapy required additional surgical interventions. Minor complications were observed in 10% of the study population. Conclusion: Intrapleural streptokinase therapy demonstrated promising outcomes in resolving retained hemothorax among patients in Pakistan. Despite the need for additional surgical interventions in some cases, this treatment modality's overall efficacy and safety profile supports its consideration as a first-line therapy for retained hemothorax in resource-limited settings.

Mutational spectrum of CFTR in cystic fibrosis patients with gastrointestinal and hepatobiliary manifestations.

Cystic fibrosis (CF) is a rare and debilitating autosomal recessive disorder. It hampers the normal function of various organs and causes severe damage to the lungs, and digestive system leading to recurring pneumonia. Cf also affects reproductive health eventually may cause infertility. The disease manifests due to genetic aberrations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aimed to screen for CFTR gene variants in Pakistani CF patients representing variable phenotypes. Clinical exome and Sanger sequencing were performed after clinical characterization of 25 suspected cases of CF (CF1-CF25). ACMG guidelines were followed to interpret the clinical significance of the identified variants. Clinical investigations revealed common phenotypes such as pancreatic insufficiency, chest infections, chronic liver and lung diseases. Some patients also displayed symptoms like gastroesophageal reflux disease (GERD), neonatal cholestasis, acrodermatitis, diabetes mellitus, and abnormal malabsorptive stools. Genetic analysis of the 25 CF patients identified deleterious variants in the CFTR gene. Notably, 12% of patients showed compound heterozygous variants, while 88% had homozygous variants. The most prevalent variant was p. (Met1Thr or Met1?) at 24%, previously not reported in the Pakistani population. The second most common variant was p. (Phe508del) at 16%. Other variants, including p. (Leu218*), p. (Tyr569Asp), p. (Glu585Ter), and p. (Arg1162*) were also identified in the present study. Genetic analysis of one of the present patients showed a pathogenic variant in G6PD in addition to CFTR. The study reports novel and reported variants in the CFTR gene in CF patients in Pakistani population having distinct phenotypes. It also emphasizes screening suspected Pakistani CF patients for the p. (Met1Thr) variant because of its increased observance and prevalence in the study. Moreover, the findings also signify searching for additional pathogenic variants in the genome of CF patients, which may modify the phenotypes. The findings contribute valuable information for the diagnosis, genetic counseling, and potential therapeutic strategies for CF patients in Pakistan.

Perceived Social Stigma, Family Support and Mental Health Issues in Individuals Living with HIV/AIDS

Background: In Pakistan, the HIV/AIDS epidemic is compounded by significant socio-economic challenges and a pervasive stigma that undermines effective treatment and prevention strategies. The psychological impacts of HIV/AIDS, such as anxiety, depression, and stress, further complicate disease management, affecting patients' willingness to adhere to treatment and disclose their status. Objective: This study aimed to assess the prevalence of mental health issues among individuals living with HIV/AIDS in Pakistan and explore the relationships between perceived social stigma, family support, and mental health outcomes. Methods: A cross-sectional study was conducted involving 150 diagnosed HIV/AIDS patients from Nankana Sahib and Faisalabad districts. Participants were selected using purposive sampling. Data were collected through validated Urdu versions of the Depression Anxiety Stress Scales (DASS), a discrimination scale, and a family support scale. Statistical analysis was performed using SPSS version 25, focusing on descriptive statistics, correlation coefficients, and linear regression models. Results: The results indicated that the mean scores for depression, anxiety, and stress were significantly high at 66.6980 ± 17.56598. A strong positive correlation was observed between perceived discrimination (DISC) and DASS scores (r = 0.890, p &lt; 0.01), while perceived family support (PFS) was negatively correlated with DISC scores (r = -0.166, p = 0.043). Regression analysis showed that increased family support significantly mitigated mental health issues, reducing the mean stress, anxiety, and depression scores among participants. Conclusion: The study highlights the critical role of family support in reducing mental health issues among HIV/AIDS patients in Pakistan. Enhancing family involvement and reducing social stigma could improve treatment adherence and overall health outcomes.

Antibiotic Resistance in Salmonella typhi Strains Isolated From Patients in Pakistan: A Hospital Database Study.

The surge in antibiotic-resistant Salmonella enterica serotype Typhistrains has led to heightened morbidity, mortality, and treatment expenses. This study aims to assess the resistance patterns of Salmonella Typhi to diverse antibiotics among patients seeking care at a tertiary hospital in Pakistan. A database from a tertiary care hospital in Pakistan was reviewed, and data on blood cultures that isolated Salmonella enterica serotype Typhi were collected. Data were collected and analyzed using Microsoft Excel (Microsoft Corporation, USA) and IBM SPSS software (IBM Corp., Armonk, NY). Demographic information of the selected data was retrieved from the hospital database, and the results showed that 63.7% were male, 36.1% were female, and 0.2% were categorized as neutered. Regarding antibiotic resistance, ampicillin exhibited the highest resistance rate (91.50%), while meropenem demonstrated the lowest (3.00%). Antibiotic sensitivity patterns also varied across different age groups, although statistical analysis indicated no significant differences. Significant associations were found between antibiotic resistance and comorbidities, as well as previous antibiotic use. Salmonella enterica serotype Typhi showed a high resistancetoampicillin and fluoroquinolones, such as ciprofloxacin. The emergence of resistance and decreased sensitivity to current first-line antibiotics necessitates a shift towards alternative options, such as third-generation cephalosporins, azithromycin, and newer antibiotics like meropenem.

Tuberculosis Co-infection among HIV/AIDS Cases Attending an Anti-retroviral Therapy Center: A Retrospective Cohort Study from Pakistan

Objective: The co-occurrence of tuberculosis (TB) and human immunodeficiency virus (HIV) results in heightened morbidity and mortality, placing an increased burden on healthcare systems. This study aims to assess the incidence and identify associated risk factors for TB/HIV co-infection, with the objective of enhancing the survival rates of co-infected patients in Pakistan. Methods: This retrospective cohort investigation took place at the Anti-Retroviral Treatment Center in Islamabad, Pakistan. Data spanning a decade (January 2006 to December 2016) were extracted from 2,542 people living with HIV using a pre-tested data extraction tool. Results: Following the exclusion of 156 ineligible participants, records of 2,386 individuals were analyzed over 4,433 person-years. The cumulative incidence and incidence rate of TB among HIV/AIDS patients were 446 (18.7%) and 0.001 cases/10,000 person-years, respectively. The majority (81%) of incident TB cases occurred within one year, predominantly manifesting as pulmonary TB. Of the TB-infected individuals, 98.6% received TB medication, with 0.7% prescribed Isoniazid prophylaxis. Significant associations with TB were identified in relation to work abroad history, patient age, and current HIV stage (P&lt;0.05). Binary logistic regression indicated a 3.1 times higher likelihood of TB infection in the anemic group compared to the non-anemic group. HIV/AIDS infection emerged as a consistent TB risk factor irrespective of CD4 count and WHO HIV staging. Conclusion: This study highlights a substantial incidence of TB co-infection among HIV patients in Pakistan, emphasizing the need for comprehensive efforts by the National AIDS Control and National TB Control Programs to effectively manage co-infection.

Thematic Analysis of Reality Therapy with Functional Neurological (Conversion) Disorder Patients in Pakistan

Thematic Analysis of Reality Therapy with Functional Neurological (Conversion) Disorder Patients in Pakistan

Transcriptomic Analysis of Alzheimer's Disease Pathways in a Pakistani Population.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is most prevalent in elderly individuals, especially in developed countries, and its prevalence is now increasing in developing countries like Pakistan. Our goal was to characterize key genes and their levels of expression and related molecular transcriptome networks associated with AD pathogenesis in a pilot case-control study in a Pakistani population. To obtain the spectrum of molecular networks associated with pathogenesis in AD patients in Pakistan (comparing cases and controls), we used high-throughput qRT-PCR (TaqMan Low-Density Array; n = 33 subjects) coupled with Affymetrix Arrays (n = 8) and Ingenuity Pathway Analysis (IPA) to identify signature genes associated with Amyloid processing and disease pathways. We confirmed 16 differentially expressed AD-related genes, including maximum fold changes observed in CAPNS2 and CAPN1. The global gene expression study observed that 61% and 39% of genes were significantly (p-value 0.05) up- and downregulated, respectively, in AD patients compared to healthy controls. The key pathways include, e.g., Amyloid Processing, Neuroinflammation Signaling, and ErbB4 Signaling. The top-scoring networks in Diseases and Disorders Development were Neurological Disease, Organismal Injury and Abnormalities, and Psychological Disorders. Our pilot study offers a non-invasive and efficient way of investigating gene expression patterns by combining TLDA and global gene expression method in AD patients by utilizing whole blood. This provides valuable insights into the expression status of genes related to Amyloid Processing, which could play potential role in future studies to identify sensitive, early biomarkers of AD in general.