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Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic acid (OCA) serves as a second-line option because of moderate UDCA nonresponsiveness and cirrhosis-related concerns. Additional therapies are necessary because of recent warnings regarding OCA usage in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC. We searched PubMed, Google Scholar, and the Cochrane Library until October 2023. We included all randomized controlled trials (RCTs) that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was change in alkaline phosphatase (ALP) levels. In contrast, the secondary outcomes were changes in gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride levels, and pruritis. We used a random-effects model to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% CI. A total of eight RCTs ( = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared with placebo for change in ALP level (SMD = -2.81, 95%CI = -4.10 to - 1.51; < 0.0001, I = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; = 0.002, I = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; = 0.006, I = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; = 0.003, I = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; = 0.07, I = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; = 0.99, I = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; = 0.60, I = 34%). Our study found a superior efficacy of PPAR agonists compared with placebo for change in ALP, GGT, TBil, and Tg levels, highlighting the potentially beneficial effect of PPAR agonists on liver health.

BackgroundChronic Hepatitis B (CHB) is a global health concern, with significant risks of liver-related complications and mortality. Antiviral treatments such as Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF) are commonly used for HBV suppression. TAF is a newer formulation designed to offer similar efficacy to TDF while improving safety profiles, especially in terms of bone and renal health. This meta-analysis aimed to compare the efficacy and safety of TAF and TDF in treating CHB.MethodsA systematic literature search was conducted in August 2023, focusing on randomised controlled trials (RCTs) comparing TAF and TDF for the treatment of CHB. Four RCTs involving 1,960 patients were included. The primary outcome was the proportion of patients achieving HBV DNA suppression to levels <15-29 IU/ml. Secondary outcomes included ALT normalisation, changes in bone mineral density (BMD), serum creatinine levels, estimated glomerular filtration rate (eGFR), and LDL cholesterol levels. Pooled data were analysed using relative risk (RR) and mean difference (MD) with 95% confidence intervals (CIs).Abstract O31 Figure 1Effect of TAF compared to TDF on virological suppression[Figure omitted. See PDF]ResultsPrimary Outcome: Both TAF and TDF demonstrated similar efficacy in achieving virological suppression, with no significant difference in HBV DNA reduction (RR=1.00; 95% CI 0.96 to 1.05; p=0.82).Secondary Outcomes:ALT Normalisation: TAF was more effective in achieving ALT normalisation (RR=1.38; 95% CI 1.16 to 1.64; p=0.0002).Bone Mineral Density (BMD): TAF showed significantly less reduction in hip (MD=1.44; 95% CI 0.98 to 1.91; p<0.00001) and spine BMD (MD=1.93; 95% CI 1.42 to 2.44; p<0.00001).Kidney Function: TAF caused less elevation in serum creatinine (MD=-0.02; 95% CI -0.03 to -0.01; p<0.00001) and less decline in eGFR (MD=3.55; 95% CI 2.97 to 4.14; p<0.0001).LDL Cholesterol: TAF was associated with higher LDL cholesterol levels compared to TDF (RR=4.95; 95% CI 1.21 to 20.29; p=0.03).ConclusionTAF demonstrated comparable efficacy to TDF in HBV DNA suppression but showed superior outcomes in terms of ALT normalisation, bone mineral density preservation, and kidney function. However, TAF led to higher LDL cholesterol levels, which may require monitoring. These findings suggest that TAF could be a safer alternative to TDF for CHB patients, particularly in those at risk for bone and renal complications. Further long-term studies are needed to confirm these results, particularly in special populations.

BackgroundPrimary Biliary Cholangitis (PBC) is a rare autoimmune liver disease that causes liver inflammation and damage, potentially leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders. Due to the limited treatment options, there is a need to explore alternative therapies. This study evaluates the efficacy and safety of PPAR agonists for PBC management.MethodsA systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor). The primary outcome was alkaline phosphatase (ALP), while secondary outcomes included GGT, ALT, AST, total bilirubin (TBil), triglycerides (Tg), and pruritus. Subgroup analyses were conducted based on the type of PPAR agonists used in the trials.ResultsThe analysis revealed that PPAR agonists significantly reduced ALP levels compared to placebo (SMD = -0.66, p = 0.0005), indicating a notable improvement in liver function. Similarly, there was a significant reduction in GGT levels (SMD = -0.45, p = 0.02), which is a marker of liver injury and cholestasis. The overall reduction in total bilirubin (TBil) was also significant (SMD = -0.77, p = 0.006), suggesting improved biliary function. Triglyceride levels showed a significant decrease with PPAR agonists (MD = -0.99, p = 0.003), consistent with the lipid-regulating effects of PPAR activation. However, no significant changes were found for ALT (p = 0.07) or AST (p = 0.99), indicating that PPAR agonists may not significantly impact these liver enzymes in PBC. Subgroup analysis demonstrated that both selective PPAR agonists (such as fenofibrate and seladelpar) and multi-subtype PPAR agonists (like bezafibrate and elafibranor) led to significant reductions in ALP and GGT compared to placebo. Interestingly, selective PPAR agonists exhibited minimal heterogeneity for TBil levels (I² = 0%), while multi-subtype agonists maintained high heterogeneity. The analysis of pruritus found no significant difference between PPAR agonists and placebo (p = 0.6), despite some trials reporting variable effects on pruritus severity.Abstract P219 Figure 1Forest plot of change in ALP levels from baseline[Figure omitted. See PDF]ConclusionPPAR agonists are effective in reducing key biochemical markers of liver dysfunction in PBC, particularly ALP, GGT, TBil, and triglycerides. However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC.

The aim of this study is to ascertain the psychological impacts of coronavirus disease (COVID-19) among the Pakistani health care workers (HCWs) and their coping strategies. This web-based, cross-sectional study was conducted among HCWs (N = 398) from Punjab Province of Pakistan. The generalized anxiety scale (GAD-7), patient health questionnaire (PHQ-9), and Brief-COPE were used to assess anxiety, depression, and coping strategies, respectively. The average age of respondents was 28.67 years (SD = 4.15), with the majority being medical doctors (52%). Prevalences of anxiety and depression were 21.4% and 21.9%, respectively. There was no significant difference in anxiety and depression scores among doctors, nurses, and pharmacists. Females had significantly higher anxiety ( = 0.003) and depression ( = 0.001) scores than males. Moreover, frontline HCWs had significantly higher depression scores ( = 0.010) than others. The depression, not anxiety, score was significantly higher among those who did not receive the infection prevention training ( = 0.004). The most frequently adopted coping strategies were religious coping (M = 5.98, SD = 1.73), acceptance (M = 5.59, SD = 1.55), and coping planning (M = 4.91, SD = 1.85). A considerable proportion of HCWs are having generalized anxiety and depression during the ongoing COVID-19 pandemic. Our findings call for interventions to mitigate mental health risks in HCWs.

Antibiotics are one of the most frequently dispensed classes of medicines. However, excessive misuse and abuse enhances antimicrobial resistance (AMR). Previous studies in Pakistan have documented extensive dispensing of ‘Watch’ and ‘Reserve’ antibiotics, which is a concern. In view of this, there is a need to assess current dispensing patterns following COVID-19 in Pakistan. A cross-sectional study was undertaken, collecting dispensing data from 39 pharmacies and 53 drug stores from November 2022 to February 2023. Outlets were principally in urban areas (60.9%), with pharmacists/pharmacy technicians present in 32.6% of outlets. In total, 11,092 prescriptions were analyzed; 67.1% of patients were supplied at least one antimicrobial, 74.3% antibiotics, 10.2% antifungals and 7.9% anthelmintics. A total of 33.2% of antimicrobials were supplied without a prescription. Common indications for dispensed antibiotics were respiratory (34.3%) and gastrointestinal (16.8%) infections, which can be self-limiting. In addition, 12% of antibiotics were dispensed for the prevention or treatment of COVID-19. The most frequent antibiotics dispensed were ceftriaxone (18.4%) and amoxicillin (15.4%). Overall, 59.2% antibiotics were ‘Watch’ antibiotics, followed by ‘Access’ (40.3%) and ‘Reserve’ (0.5%) antibiotics. Of the total antibiotics dispensed for treating COVID-19, 68.3% were ‘Watch’ and 31.7% ‘Access’. Overall, there appeared to be an appreciable number of antibiotics dispensed during the recent pandemic, including for patients with COVID-19, alongside generally extensive dispensing of ‘Watch’ antibiotics. This needs to be urgently addressed with appropriate programs among pharmacists/pharmacy technicians to reduce AMR.

COVID-19 outbreak has been accompanied by a massive infodemic, however, many vulnerable individuals such as illiterate or low-literate, older adults and rural populations have limited access to health information. In this context, these individuals are more likely to have poor knowledge, attitudes, and preventive practices related to COVID-19. The current study was aimed to investigate COVID-19's awareness of the illiterate population of Pakistan. A cross-sectional survey was conducted among illiterate Pakistanis of ages ≥ 18 years through a convenient sampling approach. The study participants were interviewed face to face by respecting the defined precautionary measures and all data were entered and analyzed using SPSS version 22 (IBM, Armonk, NY). The mean age of the study participants' (N = 394) was 37.2 ± 9.60 years, with the majority being males (80.7%). All participants were aware of the COVID-19 outbreak and television news channels (75.1%) were the primary source of information. The mean knowledge score was 5.33 ± 1.88, and about 27% of participants had a good knowledge score (score ≥ 7) followed by moderate (score 4 - 6) and poor (score ≤ 3) knowledge in 41.6%, and 31.5% of respondents, respectively. The attitude score was 4.42 ± 1.22 with good (score ≥ 6), average (score 4 - 5), and poor attitude (score ≤ 3) in 19%, 66%, and 15% of the participants, respectively. The average practice-related score was 12.80 ± 3.34, with the majority of participants having inadequate practices. COVID-19 knowledge, attitude, and preventive practices of the illiterate population in Pakistan are unsatisfactory. This study highlights the gaps in specific aspects of knowledge and practice that should be addressed through awareness campaigns targeting this specific population.

Objective: To determine the frequency of Immunohistochemical expression of P16 in low grade urothelial carcinoma patients. Study Design: Cross sectional study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from May 2018 to Jul 2019. Methodology: A total of 120 formalin-fixed and paraffin embedded blocks from patients having low grade urothelial carcinomawere included in the study and were stainedimmunohistochemically with P16 antibody. Expression of P16 was noted by two independent pathologists and nuclear stain of strong intensity was taken as positive. Results: There were 91 (76%) males and 29 (24%) females with age range from 18-85 years (mean 67.19 ± 11.5 years) female to male ratio was 1:3. P16 stain was positive in (70.8%) and negative in 37 (31%) of low gradeurothelial carcinoma cases. Conclusion: The p-16 is expressed in a significant number of urothelial carcinomas (low grade) and this marker could be used in routine practice for early identification of patients at high risk of progression to advanced stage.

Objective: To evaluate the impact of Neo-Adjuvant Chemotherapy on Pathological Complete Response rates, in patients with Triple-Negative Breast Cancer, focusing on the relationship between tumor size, nodal involvement, type of surgery, and treatment outcomes. Study Design: Prospective cohort study. Place and Duration of Study: Pakistan Navy Station Shifa Hospital, Karachi Pakistan, from Feb 2023 to Feb 2025. Methodology: A total of 88 patients with triple-negative breast cancer who received neoadjuvant chemotherapy were included. Baseline characteristics, including tumor size, nodal involvement, and type of surgery, were recorded. The chi-square test was used to compare pathological complete response rates between subgroups. A p-value of <0.05 was considered statistically significant. Results: The overall Pathological Complete Response rate was 43.18%. Nodal involvement was significantly associated with Pathological Complete Response (p=0.01), with N0 patients achieving higher response rates compared to N1 and N2 patients. Tumor size and type of surgery were not significantly associated with Pathological Complete Response (p=0.13 and p=0.30, respectively). Tumor size and type of surgery did not significantly affect outcomes. Adverse effects were observed in 21.59% of patients, with no significant impact. Conclusion: Neo-Adjuvant Chemotherapy is effective in achieving Pathological Complete Response in Triple-Negative Breast Cancer patients, particularly in those without nodal involvement.