X-linked agammaglobulinemia - first case with bruton tyrosine kinase mutation from Pakistan

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Genetic analysis showed Btk mutation 18 c.1883delCp.T628fs. To the best of our knowledge this is the first report of a case of XLA confirmed by molecular technique from Pakistan

Prevalence and risk factors associated with multi-drug resistant organisms (MDRO) carriage among pediatric patients at the time of admission in a tertiary care hospital of a developing country. A cross-sectional study

Background: The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it.Methods: A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1-18 years. For identification of MDRO (i.e., Extended Spectrum Beta-Lactamase (ESBL) producers, Carbapenem Resistant Enterobacteriaceae (CRE), Vancomycin Resistant Enterococci (VRE), Methicillin Resistant Staphylococcus aureus (MRSA), Multidrug-resistant (MDR) Acinetobacter species and MDR Pseudomonas aeruginosa), nasal swabs and rectal swabs or stool samples were cultured on specific media within 72 h of hospitalization. Data was collected on a predesigned structured questionnaire on demographics, prior use of antibiotics for \u3e 48 h in the last 6 months, history of vaccination in last 6 months, exposure to health care facility regardless of the time of exposure, ICU stay for \u3e 72 h, and about the prior use of medical devices (urinary catheter, central venous lines etc.) in last 1 year. Statistical analysis was performed by Standard statistical software.Results: Out of 347 participants, 237 (68.3%) were found to be MDRO carriers. Forty nine nasal swabs from 346 children (14.2%) showed growth of MRSA. The majority of the stool/rectal swabs (n = 222 of 322; 69%) collected were positive for MDRO. The most isolated species were ESBL Escherichia coli 174/222 (78.3%) followed by ESBL Enterobacter species 37/222 (16.7%) and ESBL Klebsiella pneumoniae 35/222 (15.8%). On univariate analysis, none of the risk factors showed statistically significant association with MDRO carriage.Conclusion: Overall, a high prevalence of MDRO carriage was identified among admitted pediatric patients. Implementation of systematic screening may help to identify true burden of MDROs carriage in the health care settings

Efficacy of intervention towards blood donation to increase voluntary blood donation: a systematic review

Although blood is the essence of life, and is one of the most precious donations; blood transfusion services are facing shortage of blood all over the world. A significant percentage of people have false beliefs about blood donation. Increase in the level of knowledge and correction of false beliefs should be the top most priority. Therefore, studying factors contributing to their knowledge, attitude and practice of blood donation is essential. There are studies that investigated the effectiveness of interventions or procedure changes in blood donation settings on outcomes including donor deferral, disclosure of risk factors, and rates of errors and omissions. Researchers also identified several interventions to improve donor compliance that have been tested in blood donation settings and provided evidence for the effectiveness of computerized interviews in improving detection of risk factors. Interventions can utilize the processes of change (POC) measure to guide stage matched interventions to encourage use of relevant experiential and behavioral strategies to increase blood donation. Interventions to recruit and retain blood donors in the general population have been classified into five approaches: motivational, reminders/asking, measurement of cognitions, incentives, and preventing vasovagal reactions. Effective recruitment and retention are two different processes and may require different approaches. For example, retention may be influenced more by interventions that focus on actions during or after donation rather than interventions prior to the blood donation appointment

Evaluation of genetic diversity in Sulla coronaria from different geographical populations in Tunisia by inter simple sequence repeat (ISSR)

Five oligonucleotides generating 116 markers complementary to simple sequence repeats were used in order to characterize wild and cultivated ecotypes of Sulla coronaria and assess genetic diversity suitable in breeding programs. While analysing populations, a large genetic variability was revealed and supported by the preferentially allogamous mating system of the species. Moreover, the highest level of intra-population variations (Hpop/Hsp = 69.9) either of wild or cultivated accessions have been strongly evidenced by a significant adaptation to variety of habitats. In addition, the structure of populations was independent from the bioclimatic stages and was not affected by environmental factors as shown by the non correlation between the geographic and the Nei and Li’s genetic distances (r= 0.461 and p=0.068>0.05). The unweighted pair group method with arithmetic mean (UPGMA) genetic relationships showed that some local spontaneous accessions characterised by an orthotropic port (Jebel Zit and Beja) were also molecularly similar to other cultivars.Key words: Sulla coronaria, wild and cultivated forms, intra and inter-populations variability, microsatellites (ISSRs), bioclimatic stages

Prevalence of Bombay phenotype among Bangladeshi ‘O’ blood group population

Background: The Bombay blood group, a rare type often confused with ‘O’, poses a critical transfusion risk, requiring specific compatibility with Bombay (Oh) blood. With a lack of data in Bangladesh, this study aimed to establish a comprehensive database for the rare Bombay phenotype, crucial for transfusion safety. Objective was to determine the frequency prevalence of Bombay phenotype among ‘O’ blood group individuals. Methods: A cross-sectional study conducted at Bangabandhu Sheikh Mujib Medical University from January 2020 to June 2021 involved, aseptic collection of 3 ml venous blood sample, with forward and reverse blood grouping revealing a ‘O’ phenotype. Utilizing anti-H lectin resolved discrepancies and confirmed the absence of ‘H’ antigen in individuals with Bombay blood groups. Blood samples of Bombay phenotype individuals showed the following reactions: anti-A (-), anti-B (-), anti-AB (-), anti-H (-), A cells 4+, B cells 4+, O cells 4+. Results: Among 10,000 individuals with apparent blood group ‘O’, 99.97% were identified as ‘O’ blood type, while only 0.03% exhibited the rare Bombay blood group. ABO and Rh-D blood group frequencies varied over the study period, with B +ve at the highest (28.31%) and AB -ve at the lowest (0.21% to 0.23%). Overall, O +ve had the highest frequency (97.29%), and Bombay blood group was rare, with ‘O’ dominating at 99.97%. Conclusions: The study identified a 0.03% prevalence of the Bombay phenotype. Due to its potential confusion with ‘O’ blood group, transfusing ‘O’ blood to Bombay individuals carries a substantial risk of severe hemolytic reactions, including fatal consequences

Trajectory of Change in the Severity of Symptoms in Patients with Fibromyalgia over 24 Months: Exploratory Analyses of a Combination Pharmacological Intervention

Symptoms of fibromyalgia (FM) fluctuate and vary in severity. The current study aimed to evaluate the efficacy of palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) in FM patients over a 24-month period and to investigate the mediating function of pain catastrophizing subdomains in unfavorable relationships with disease severity levels in patients with FM. Patients were evaluated at baseline, after 12 months, and after 24 months, using different patient-reported measures (FIQR, FASmod, PSD, and PCS) to distinguish different levels of FM disease severity. A reduction of 30% or more from baseline was considered clinically important (“markedly improved”). A multivariate analysis was performed to identify the variables predictive of an FIQR reduction. Twenty-two patients (28.6%) were classified as “markedly improved,” 16 patients (20.8%) as “slightly/moderately improved,” and 39 patients (50.6%) as “not improved.” The FIQR, FASmod, and PSD scores were significantly reduced at 24 months. The pain magnification domain score of the PCS was the only variable predictive of worse FIQR scores (Wald coefficient: −2.94; p = 0.047). These results suggest a potential long-term therapeutic role for the PEA + ALC combination, with pain magnification being the primary predictor of poor efficacy

The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan

Background: Primary Immunodeficiency Disorders (PIDs) are well-known disorders in the West. but the recognition and diagnosis of these disorders is challenging in developing countries. We present the spectrum of PIDs seen at a tertiary care center in Pakistan, identified using clinical case definitions and molecular methods.Methods: A retrospective chart review of children suspected to have PID was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan from 2010 to 2016. Data on demographics, clinical features, family history of consanguinity, sibling death, details of laboratory workup done for PID and molecular tests targeted panel next generation sequencing (NGS) or whole exome sequencing (WES) performed at the Geha laboratory at Boston Children\u27s Hospital, USA was collected. The study was exempted from the Ethical Review Committee of AKUH.Results: A total of 43 children visited the hospital with suspected PID during the study period. Genetic testing was performed in 31/43 (72.1%) children. A confirmed diagnosis of PID was established in 20/43 (46.5%) children. A pathogenic gene variant was identified in 17(85%) of the 20 confirmed cases (Table 1). Twelve (60%) of the confirmed cases of PID were male. The most common presenting symptom was recurrent diarrhea 11/20 (55%). The mean (±S.D) age of the cases at the time of diagnosis was 4.2 (±4.1) years. Chronic granulomatous disease (CGD) was the most common 6/20 (30%) disorder, followed by severe combined immunodeficiency (SCID) 3/20 (15%), leukocyte adhesion deficiency (LAD) 3/20 (15%), agammaglobulinemia/hypogammaglobulinemia 3/20 (15%), and Hermansky-Pudlak Syndrome (HPS) 2/20 (10%). Wiskott-Aldrich Syndrome, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome (ICF 2), Trichohepatoenteric syndrome (TRES), and C3 deficiency were each diagnosed once {1/20 (4.3%) each} (Table 1). Of these 20 confirmed cases, almost all 19/20 (95%) had a family history of consanguinity. Sibling death was reported in 5/20 (25%) of these cases. Five out of the 20 (25%) children died over the 7-year period for various reasons.Conclusion: PIDs are not uncommon in Pakistan; their diagnosis may be missed or delayed due to the overlapping of clinical features of PID with other diseases and a lack of diagnostic facilities. There is a need to build capacity for early recognition and diagnosis of PIDs to decrease morbidity and mortality

Response of extensively drug resistant salmonella typhi to treatment with meropenem and azithromycin, in Pakistan

Introduction: Salmonella Typhi is one of the leading health problems in Pakistan. With the emergence of extensively drug resistant (XDR) Salmonella Typhi, treatment options are limited. Here we report the clinical manifestations and the response to treatment of patients with XDR Typhoid fever. The patients were treated with either Meropenem or Azithromycin or a combination of both.Methods: We reviewed the records of culture confirmed XDR typhoid who visited Aga Khan University Hospital (AKUH), Karachi and Aga Khan Secondary Care Hospital, Hyderabad from April 2017 to June 2018. Symptoms developed during disease, unplanned treatment extension and complications developed while on antimicrobials was recorded. Means with standard deviation were calculated for duration of treatment, time to defervescence, and cost of treatment.Results: Records of 81 culture confirmed XDR typhoid patients admitted at the AKU hospitals were reviewed. Most, (n = 45; 56%) were male. Mean age of the cases was 8.03 years with range (1-40). About three quarter (n = 66) of the patients were treated as inpatient. Fever and vomiting were the most common symptoms at the time of presentation. Oral azithromycin alone (n = 22; 27%), intravenous meropenem alone (n = 20; 25%), or a combination of azithromycin and meropenem (n = 39; 48%) were the options used for treatment. Average (95% confidence interval) time to defervescence was 7.1(5.5-8.6), 6.7(4.7-8.7), and 6.7(5.5-7.9) days for each treatment option respectively whereas there were 1,0 and 3 treatment failures in each treatment option respectively. Average cost of treatment per day for azithromycin was US$5.87 whereas it was US$88.46 for meropenem.Conclusion: Patients treated with either Azithromycin, Meropenem alone or in combination showed similar time to defervescence. Because of the lower cost of azithromycin, it is preferable in lower socio-economic areas. Background estimates for power calculation can be made for more robust clinical trials using this observational data