Real-World Evidence to Evaluate the Efficacy and Safety of Vonoprazan in Gastrointestinal Disorders in the Pakistani Population.

BACKGROUND AND AIM: While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population. METHODS: This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA. RESULTS: Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the second week of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients. CONCLUSIONS: The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

Correction: Real-World Evidence to Evaluate the Efficacy and Safety of Vonoprazan in Gastrointestinal Disorders in the Pakistani Population.

[This corrects the article DOI: 10.7759/cureus.48994.].

Comprehensive genetic screening reveals wide spectrum of genetic variants in monogenic forms of diabetes among Pakistani population.

BACKGROUND: Monogenic forms of diabetes (MFD) are single gene disorders. Their diagnosis is challenging, and symptoms overlap with type 1 and type 2 diabetes. AIM: To identify the genetic variants responsible for MFD in the Pakistani population and their frequencies. METHODS: A total of 184 patients suspected of having MFD were enrolled. The inclusion criterion was diabetes with onset below 25 years of age. Brief demographic and clinical information were taken from the participants. The maturity-onset diabetes of the young (MODY) probability score was calculated, and glutamate decarboxylase ELISA was performed. Antibody negative patients and features resembling MODY were selected (n = 28) for exome sequencing to identify the pathogenic variants. RESULTS: A total of eight missense novel or very low-frequency variants were identified in 7 patients. Three variants were found in genes for MODY, i.e. HNF1A (c.169C>A, p.Leu57Met), KLF11 (c.401G>C, p.Gly134Ala), and HNF1B (c.1058C>T, p.Ser353Leu). Five variants were found in genes other than the 14 known MODY genes, i.e. RFX6 (c.919G>A, p.Glu307Lys), WFS1 (c.478G>A, p.Glu160Lys) and WFS1 (c.517G>A, p.Glu173Lys), RFX6 (c.1212T>A, p.His404Gln) and ZBTB20 (c.1049G>A, p.Arg350His). CONCLUSION: The study showed wide spectrum of genetic variants potentially causing MFD in the Pakistani population. The MODY genes prevalent in European population (GCK, HNF1A, and HNF4a) were not found to be common in our population. Identification of novel variants will further help to understand the role of different genes causing the pathogenicity in MODY patient and their proper management and diagnosis.

Diagnostic Accuracy of Sputum Microscopy in Comparison With GeneXpert in Pulmonary Tuberculosis.

Background Tuberculosis (TB) is a major health problem. In Pakistan, the diagnosis of pulmonary tuberculosis mainly relies on acid-fast bacilli (AFB) smear microscopy and Xpert® MTB/RIF assay (Cepheid Inc., Sunnyvale, CA) - a nucleic acid amplification test - where available. There is a wide variation in the reported sensitivity of Ziehl-Neelsen (ZN) smear microscopy across previous studies. This study aimed to determine the accuracy of sputum ZN smear microscopy in diagnosing pulmonary tuberculosis as compared with the sputum GeneXpert (Xpert MTB/RIF assay) as the reference test. Materials and methods This is a retrospective cross-sectional study conducted in the outpatient department of the Pakistan Institute of Medical Sciences. This study included 326 patients, aged 12 years and above, who had their sputum samples tested for ZN smear microscopy and GeneXpert during the period January to June 2019. Patients' demographic details, sputum ZN smear microscopy, and GeneXpert test results were collected for data analysis. A case of pulmonary tuberculosis was defined as a patient with positive sputum GeneXpert test result. Results Out of the 326 patients, GeneXpert detected MTB deoxyribonucleic acid (DNA) in 50 patients and ZN smear microscopy detected AFB in 30 patients. There was a marginal male predominance among GeneXpert positive cases. Adolescents were the least affected age group. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of ZN smear microscopy were 60%, 100%, 100%, 93.24%, and 93.87%, respectively. The positive likelihood ratio was infinite whereas the negative likelihood ratio was 0.4. The area under curve (AUC) for ZN smear microscopy was 0.800 and receiver operating characteristic (ROC) curve analysis revealed a diagonal straight line closer to the left upper corner. Conclusion Sputum ZN smear microscopy is a highly specific but moderately sensitive test for the diagnosis of pulmonary tuberculosis. This study recommends the sputum GeneXpert MTB/RIF test to avoid a missed diagnosis of smear-negative pulmonary TB.

Antibiotic Susceptibility Patterns of Salmonella Typhi and Salmonella Paratyphi in a Tertiary Care Hospital in Islamabad.

Background Enteric fever is a serious public health problem in Pakistan. Growing problem of drug-resistant Salmonella strains and outbreak of ceftriaxone-resistant Salmonella typhi in Hyderabad during 2016-2017 is concerning. This study aimed to determine the antibiogram profile of Salmonella typhi and Salmonella paratyphi isolated from blood cultures of patients presenting in Pakistan Institute of Medical Sciences (PIMS), Islamabad. Materials and methods A retrospective cross-sectional study conducted in PIMS. A case of enteric fever was defined as a patient with blood culture positive for either S. typhi or S. paratyphi. Demographics and antibiogram profile of the 664 cases who presented during 2012-2018 were included in this study. Results Out of 664 cases, S. typhi was isolated from 528 and S. paratyphi was isolated from 136 cases. Males accounted for the majority of the cases (n = 440, 66.3%). Clustering of the cases was observed in young adults (18-25 years). Incidence was highest during months of summer and monsoon (May-September). Most of the S. typhi isolates were resistant to the first-line antibiotics (amoxicillin 57.6%, co-trimoxazole 61.4%, chloramphenicol 46.9%) and ciprofloxacin (62.7%). Antibiotic resistance rates were lowest for imipenem (3.8%) and ceftriaxone (4.4%). Among S. typhi isolates tested for all first-line antibiotics, 44.6% (149/334) were multidrug-resistant (MDR). In contrast, only 12.2% (11/90) of the S. paratyphi isolates were MDR. 0.7% (2/283) of the tested S. typhi isolates were extensively drug-resistant (XDR). XDR strains were sensitive to imipenem. There was an overall reduction in first-line antibiotic resistance rates from 2012 to 2018. Conclusion S. typhi accounted for the majority of the cases of enteric fever. Most S. typhi isolates were resistant to first-line antibiotics. S. paratyphi exhibited lower antibiotic resistance rates. This study recommends third-generation cephalosporins for empirical therapy and for treatment of MDR cases of enteric fever. Imipenem should be reserved for the treatment of XDR Salmonella cases. A decreasing trend in first-line antibiotic resistance rates over time is promising. Antibiotic stewardship is the need of the hour.

Dataset of knowledge, attitude, practices and psychological implications of healthcare workers in Pakistan during COVID-19 pandemic.

The COVID-19 pandemic has created a global health emergency and has a huge impact on the health care workers, especially on their mental health. The dataset presented was an assessment of COVID-19 related knowledge, attitude, practices and its effects on the mental health of frontline healthcare workers in Pakistan. The data were collected using a snowball sampling technique. A questionnaire was developed assessing sociodemographic characteristics (6 items), knowledge (11 items), attitude (5 items), practices (6 items), information sources (1 item) and psychological implications (12 items) and distributed using online tools. The dataset includes 476 healthcare workers in Pakistan. The dataset will help to prevent and curb the spread of COVID-19 among health workers and contribute to policymakers. Furthermore, our dataset provides detailed insights into different risk factors of psychological problems, and it may be served as the reference for various in-depth surveys.

Effect of COVID-19 lockdown on patients with chronic diseases.

BACKGROUND AND AIMS: We sought to measure the effect of lockdown, implemented to contain COVID-19 infection, on routine living and health of patients with chronic diseases and challenges faced by them. METHODS: A semi-structured online questionnaire was generated using "Google forms" and sent to the patients with chronic diseases using WhatsApp. Data were retrieved and analyzed using SPSS. RESULTS: Out of 181 participants, 98% reported effect of lockdown on their routine living while 45% reported an effect on their health. The key challenges due to lockdown were to do daily exercise, missed routine checkup/lab testing and daily health care. CONCLUSION: It is important to strategize the plan for patients with chronic diseases during pandemic or lockdown.

Economic burden of dengue in four major cities of Pakistan during 2011.

OBJECTIVE: To assess the economic burden of dengue infection by calculating cost per patient and disability adjusted life years lost. METHODS: The cross-sectional study was conducted in Islamabad, Lahore, Faisalabad and Karachi from July 2012 to March 2013. Residential addresses and telephonic numbers of dengue patients were taken from the records of Pakistan Institute of Medical Sciences, Islamabad, Mayo and Ganga Ram Hospital, Lahore, Civil Hospital, Karachi, and Allied Hospital, Faisalabad. A total of 250 dengue confirmed cases - 50 from each hospital - were randomly selected. Information regarding duration of illness and out-of-pocket expenses were collected to estimate the direct cost, while indirect cost (number of work days missed by the patient) was calculated from disability adjusted life years using Murray's formula. RESULTS: Overall, there were 162(65%) men and 88(35%) with a mean age of 30.4±13.5years. More than half 138(55%) were below 30 years of age. Socio-economically, 145(58%) belonged to low, 70(28%) middle and 35(14%) to high socioeconomic groups. Of the total, 210(84%) cases had dengue fever followed by 32(12.8%) dengue haemorrhagic fever and 8(3.2%) dengue shock syndrome cases. Average duration of illness was 32±7.1 days. Overall direct cost per patient was Rs.35,823 (US$358) and average pre-hospitalisation, hospitalisation and post-hospitalisation was Rs.6154, Rs.21,242 and Rs.8,427 respectively. The overall disability adjusted life years per million population was 133.76. CONCLUSIONS: Although the government had provided free treatment for dengue in public-sector hospitals, still patients had to pay Rs.21,242 during hospital stay, resulting in substantial burden which needs to be addressed.

Dengue knowledge and its management practices among physicians of major cities of Pakistan.

OBJECTIVE: To assess knowledge and practices related to dengue management among physicians. METHODS: The cross-sectional study was conducted at hospitals in Islamabad, Lahore, Faisalabad, Peshawar, Quetta and Karachi between June and December 2012Physicians from public and private sectors filled a self-administered questionnaire about dengue knowledge and its management practices. A maximum score of 100 was assigned to the knowledge portion. Data was analysed using SPSS 15. RESULTS: A total of 400 subjects participated in the study; 200(50%) each from public and private hospitals. Of them, 223(56%) were males; 268(67%) were in the 21-30 years age bracket. The highest score was recorded in Quetta 67 followed by 65 in Karachi, 62 in Lahore, Faisalabad, Peshawar and 59 in Islamabad. Of the total, 200 (50%) were not aware that leucopenia is a criterion for diagnosing probable dengue. Similarly 140 (35%) did not know the criteria for diagnosing dengue haemorrhagic fever and warning signs of severe dengue. Total of 204 (51%) were not aware of the criteria for discharging of the admitted cases. There was no significant difference between dengue knowledge of the physicians belonging to public and private sectors (p>0.05). CONCLUSIONS: Quite a large number of physicians lacked knowledge of probable diagnosis of dengue and appropriate time to discharge the patients.