Investigating the Association Between Type 2 Diabetes Mellitus and Pathological Responses Among Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: The relationship between type 2 diabetes mellitus (T2DM) and pathological responses after neoadjuvant chemotherapy (NACT) is controversial. In this study, we aim to determine the association of pathological responses in breast cancer women with T2DM after receiving NACT. METHODS: Medical records of breast cancer women with T2DM who received NACT from January 2016 to January 2021 at the medical center in the Gujranwala Institute of Nuclear Medicine and Radiotherapy, Pakistan, were identified and retrieved retrospectively. Variables, including pathological responses, diabetes status, and other clinical data, were collected. Patients were grouped as diabetic and nondiabetic based on the doctor's diagnosis or the diabetic's medication history recorded upon the breast cancer diagnosis. Factors influencing the pathological complete response (pCR) were determined using multivariate logistic regression utilizing IBM SPSS Statistics (version 20). RESULTS: A total of 1372 patient files who received NACT and breast cancer surgery from January 2016 to January 2021 were selected. Out of 1372 breast cancer women receiving NACT, 345 (25.1%) had pre-existing diabetes, while 1027 (74.85%) were without pre-existing diabetes. The most common molecular subtypes of breast cancer were luminal A and B. Two hundred fifty-eight patients (18.8%) had a pCR after receiving NACT. The pCR in diabetic patients was 3.9%, and in nondiabetes, 14.9%. Most women had a pathological partial response (pPR) after the NACT 672 (48.9%). The pPR in diabetic patients was 11.0%, and in nondiabetic patients, it was 38.0%. In nondiabetics, the odds of achieving pPR increase more than pathological no response after the NACT with odd ratio: 1.71 (95% confidence interval: 1.24-2.37). The probability of pCR in patients with luminal B was 1.67 times higher than that in patients with triple-negative breast cancer with odd ratio: 1.67, 95% confidence interval (1.00-2.79), P = 0.05. CONCLUSIONS: The results of the study show that T2DM may have an adverse impact on pCR and pPR following NACT and surgery. Further investigation is needed to explore how changes in blood glucose levels over time impact pathological responses.

Tuberculosis (TB) treatment challenges in TB-diabetes comorbid patients: a systematic review and meta-analysis.

BACKGROUND: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results. RESULTS: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p < .01 and HR 0.93, 95% CI 0.70-1.04, p = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), p < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate (I2 = 55.79%). CONCLUSIONS: A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.

A Systematic Critical Review of Clinical Pharmacokinetics of Torasemide.

PURPOSE: Torasemide is a potassium-sparing loop diuretic used to treat fluid retention associated with congestive heart failure and kidney and hepatic diseases. This systematic review was conducted to combine all accessible data on the pharmacokinetics (PK) of torasemide in healthy and diseased populations, which may help clinicians avert adverse drug reactions and determine the correct dosage regimen. METHODS: Four databases were systematically searched to screen for studies associated with the PK of torasemide, and 21 studies met the eligibility criteria. The review protocol was registered in the PROSPERO database (CRD42023390178). RESULTS: A decrease in maximum plasma concentration (C max ) was observed for torasemide after administration of the prolonged-release formulation in comparison to that after administration of the immediate-release formulation, that is, 1.12 ± 0.17 versus 1.6 ± 0.2 mcg/mL. After administering an oral dose of torasemide, a 2-fold increase in the area under the concentration-time curve (AUC) was reported in patients with congestive heart failure compared with the healthy population. Moreover, the patients with renal failure (clearance < 30 mL/min) showed an increase in value of AUC 0-∞ that is, 42.9 versus 8.091 mcg.h -1 .mL -1 compared with healthy subjects. In addition, some studies have reported interactions with different drugs, in which irbesartan showed a slight increase in the AUC 0-∞ of torasemide, whereas losartan and empagliflozin did not. CONCLUSIONS: The current review summarizes all available PK parameters of torasemide that may be beneficial for avoiding drug-drug interactions in subjects with renal and hepatic dysfunction and for predicting doses in patients with different diseases.

The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis.

Background: The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression. Aim: To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients. Methodology: The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process. Results: Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p < 0.001). Heterogeneity observed among included studies was moderate (I2 = 38%). No significant change was observed in the results after sub-group analysis by study design (HR 0.81, 95% CI: 0.61-0.96, p < 0.000). In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients (HR 0.46, 95% CI: 0.27-0.67, p < 0.001). Conclusion: The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression.

A systematic review on the clinical pharmacokinetics of vildagliptin in healthy and disease populations.

INTRODUCTION: Vildagliptin, a dipeptidyl peptidase-4 inhibitor, is indicated to cure type 2 diabetes mellitus (T2DM). This systematic literature search aims to assess the current knowledge about the clinical pharmacokinetics (PK) of vildagliptin to provide recommendations for clinical use to prevent the harmful effects of this drug. METHODS: The PubMed, Science Direct, EBSCO, Cochrane Central Register of Controlled Trials, and Google Scholar databases were screened for articles related to the clinical PK of vildagliptin using systematic search strategies. RESULTS: The literature search identified 2118 records, among which 28 were subsumed in this systematic review that fulfilled the inclusion standards. CONCLUSIONS: This systematic review can help dose optimization among critically ill patients (e.g. renal impairment) without exposing them to the drug's toxic effects.

Clinical pharmacokinetics of nebivolol: a systematic review.

Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC0-∞) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (Cmax) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC0-∞ of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher Cmax, AUC0-∞ and half-life (t1/2) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.

Emphysematous Osteomyelitis Involving the Spine, a Case of a Rare Form of Osteomyelitis.

Gas-forming bacteria like Staphylococcus aureus (SA), along with the worrisome infections it causes, can lead to a fairly overlooked but lethal complication, called emphysematous osteomyelitis (EO). It is a condition characterized by the infection of bones complicated by the presence of gas-forming organisms. Here, we present a 50-year-old woman with insulin-dependent type 2 diabetes, who presented with cough, high-grade fevers, rigors, chills, and back pain from the last seven days. Laboratory tests revealed elevated inflammatory markers and a hyperosmolar hyperglycemic state. Sputum smear and blood cultures both reported the presence of SA. The presence of air foci in the third lumbar spine vertebra (L3) and the surrounding soft tissue was confirmed by computed tomography (CT). The posterior elements were spared, and the vertebral height and intervertebral disc were preserved. The extent of the damage done to the bone was analyzed by magnetic resonance imaging (MRI). The findings showed transverse relaxation time (T2) and short tau inversion recovery (STIR) sequences, consistent with the diagnosis of EO. She was put on strict glucose monitoring and a combination of intravenous antibiotics for three weeks followed by two weeks of oral therapy. Her symptoms improved with conservative management and reported no recurrence of any symptom of such type ever since.

Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations.

The evolution in the development of drugs has increased the popularity of physiologically based pharmacokinetic (PBPK) models. This study seeks to assess the PK of metoprolol in populations with healthy, chronic kidney disease (CKD), and acute myocardial infarction (AMI) conditions by developing and evaluating PBPK models. An extensive literature review for identifying and selecting plasma concentration vs time profile data and other drug-related parameters was undergone for their integration into the PK-Sim program followed by the development of intravenous, oral, and diseased models. The developed PBPK model of metoprolol was then evaluated using the visual predictive checks, mean observed/predicted ratios (Robs/pre), and average fold error for all PK parameters, i.e., the area under the curve (AUC), maximal plasma concentration, and clearance. The model evaluation depicted that none of the PK parameters were out of the allowed range (2-fold error) in the case of the mean Robs/pre ratios. The model anticipations were executed to determine the influence of diseases on unbound and total AUC after the application of metoprolol in healthy, moderate, and severe CKD. The dosage reductions were also suggested based on differences in unbound and total AUC in different stages of CKD. The developed PBPK models have successfully elaborated the PK changes of metoprolol occurring in healthy individuals and those with renal and heart diseases (CKD & AMI), which may be fruitful for dose optimization among diseased patients.

Scar Epilepsy as a Complication of Subarachnoid Hemorrhage in a Patient With Adult Polycystic Kidney Disease: A Case Report.

Polycystic kidney disease (PKD) is the most common hereditary disorder of kidneys. In adults, PKD1 gene mutation almost always signifies its subtype, autosomal dominant polycystic kidney disease (ADPKD), or adult polycystic kidney disease. ADPKD is a multisystemic disorder giving rise to renal and extra-renal manifestations. The renal shutdown is the most feared renal complication while the development of intracranial aneurysms is considered the most lethal extra-renal feature. This can be attributed to the increased risk of rupture associated with aneurysms leading to a condition called subarachnoid hemorrhage (SAH). While being notorious for the subtle situations SAH often leads to, its association with the onset of seizures is a matter of high clinical significance. We present a patient with a kidney disorder (ADPKD) that has led to the onset of epilepsy. Five years after the diagnosis of ADPKD, he developed an aneurysm in the right internal carotid artery, for which he was treated conservatively. After four months, he presented with the onset of symptoms of SAH, which was confirmed by computed tomography angiography. Clipping was unable to be performed, and the patient was treated conservatively, this time as well. Recently, the patient presented with the onset of generalized tonic-clonic seizures, unable to be controlled with single anti-epileptics. He was stabilized by dual intravenous antiepileptics but on further workup, he was found to have a recurrence of a berry aneurysm for which he was referred to a neurosurgeon for a clipping procedure to be performed. The operation was successful, but the patient was still found to be an epileptic for which he was discharged with a long-term course of double anti-epileptics.

Hypoplastic Myelodysplastic Syndrome: Symptom of Methotrexate Toxicity in Rheumatoid Arthritis.

Methotrexate is the conventional disease-modifying anti-rheumatic drug (DMARD) which is considered the drug of choice in the treatment of rheumatoid arthritis, but its prolonged use without monitoring leads to a number of complications involving different body systems. The toxic effects of long-term methotrexate (MTX) therapy mainly involve the liver, skin, gastrointestinal tract (GIT) and bone marrow. In the bone marrow, it mainly causes suppression of normal functionality, leading to the formation of abnormal blast cells and dysplasia. In this case report, we present a male patient with symptoms of hoarseness, fatigue and abnormal bleeding all of which can be affiliated with methotrexate-induced hypoplastic myelodysplasia. As pancytopenia can be a lethal complication of MTX toxicity, it is important to monitor the therapy and dosage of methotrexate so that in case of any unforeseen development of a complication vital steps may be taken to diagnose and treat it in time. Regarding our patient, after thorough history taking and undergoing extensive hematological workup, the diagnosis of MTX-induced hypoplastic myelodysplasia was made. His symptoms improved on withholding the drug methotrexate from his active regimen and adding folinic acid and colony-stimulating factors.

Clinical pharmacokinetics of cefixime: a systematic review.

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration (Cmax), area under the curve (AUC), clearance (CL), and time to reach Cmax (tmax). A dose-dependent increase in AUC and Cmax of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Assessment of risk factors associated with potential drug-drug interactions among patients suffering from chronic disorders.

Patients suffering from chronic diseases are more likely to experience pDDIs due to older age, prolonged treatment, severe illness and greater number of prescribed drugs. The objective of the current study was to assess the prevalence of pDDIs and risk factors associated with occurrence of pDDIs in chronic disease patients attending outpatient clinics for regular check-ups. Patients suffering from diabetes, chronic obstructive pulmonary disease (COPD), stroke and osteoporosis were included in the study. This study was a cross sectional, observational, prospective study that included 337 patients from outpatient clinics of respiratory ward, cardiac ward and orthopedic ward of Nishter Hospital Multan, Pakistan. The mean number of interactions per patient was 1.68. A greater risk for occurrence of pDDI was associated with older age ≥ 60 years (OR = 1.95, 95% CI = 1.44-2.37, p<0.001); polypharmacy (≥ 5 drugs) (OR = 3.74, 95% CI 2.32-4.54, p<0.001); overburden (OR = 2.23, 95% CI = 1.64-3.16, p<0.01); CCI score (OR = 1.28, 95% CI = 1.04-1.84, p<0.001); multiple prescribers to one patient (OR = 1.18, 95% CI = 1.06-1.41, p<0.01); and trainee practitioner (OR = 1.09, 95% CI = 1.01-1.28, p<0.01). Old age, polypharmacy, overburden healthcare system, higher comorbidity index, multiple prescribers to one patient and trainee practitioner were associated with increased risk of occurrence of pDDIs in chronic disease patients.

Clinical pharmacokinetics of terbutaline in humans: a systematic review.

Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (Cp) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (Tmax) was prolonged, and maximum plasma concentration (Cmax) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the Cp of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions.

Disposal Practices of Expired and Unused Medications Among Households in Punjab, Pakistan.

BACKGROUND: The practice of disposing expired or unused medications by different households is generally not considered and is largely neglected. OBJECTIVE: The study was carried out to determine the disposal practices regarding expired and unused medications in rural areas of Punjab, Pakistan. METHODS: The study was conducted by interviewing different households and students (rural areas) from different universities in Punjab, Pakistan. The sample size was 676 and the questionnaire was used for data collection. RESULTS: Out of 676 members, 552 (81.6%) had medications at the time of the visit. Only 14.5% (n= 80) were taking medication. Only 14.5% (n = 80) kept medication because the treatment was still in progress with the patients while 85.5% (n= 472) had medications that should be discarded. The main reasons for keeping the unused medications at home were completed treatment 34.7% (n= 164) after recovering from ailment. About 60.57% of female disposed the drugs in domestic trash while majority of male participants (48.72%) buried the drugs in the ground. Over 80% of respondents (n = 542) were unaware of the disposal methods. Almost half of the participants (n= 322) had no information about the impact of improper disposal. Statistically significant variations (p<0.001) were observed in the disposal practices depending on gender, age, education and occupation. CONCLUSION: Improper disposal of medication is a common practice in rural areas of Punjab, Pakistan. The launch of public education programs and the development of drug disposal facilities are very necessary to protect the environment and community health.

A review on the clinical pharmacokinetics of hydralazine.

INTRODUCTION: Hydralazine is a vasodilator used to treat hypertension, pre-eclampsia, and heart failure. The current article reviews the clinical pharmacokinetics (PK) of hydralazine, which can be useful for clinicians in optimizing its dose and dosing frequency to avoid adverse effects and unexpected interactions that could risk patients' lives. AREAS COVERED: This review has summarized the PK parameters for hydralazine after performing an extensive literature search. It includes 20 publications that were selected after applying eligibility criteria out of a pool of literature that was searched using Google Scholar, PubMed, Cochrane Central, and EBSCO databases. The included studies consisted of concentration vs. time profiles of hydralazine. If the PK data were not tabulated in the given study, the concentration vs. time profiles were scanned for the extraction of the PK data. The PK parameters were calculated by applying a non-compartmental analysis (NCA). EXPERT OPINION: The current review will aid clinicians in understanding hydralazine PK in different disease populations. This clinical PK data might also be helpful in the development of a pharmacokinetic model of hydralazine.

Clinical pharmacokinetics of nadolol: A systematic review.

WHAT IS KNOWN AND OBJECTIVE: Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of nadolol in humans and this can be beneficial for the clinicians in dosage adjustments. METHODS: Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review. RESULTS AND DISCUSSION: The area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of nadolol increased in a dose-dependent manner. The t½ of nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability. WHAT IS NEW AND CONCLUSION: Since, there is no previous report of a systematic review on the PK of nadolol, the current review encompasses all the relevant published articles on nadolol in humans. The analysis and understanding of PK parameters (AUC, Cmax , and t½) of nadolol may be helpful in the development and evaluation of PK models.

Barriers and facilitators to pharmacovigilance activities in Pakistan: A healthcare professionals-based survey.

The timely reporting of adverse drug reactions (ADRs) could improve pharmacovigilance (PV) in a healthcare system. However, in almost all healthcare systems barriers exist that lead to the underreporting of ADRs. The objective of this study was to identify the barriers and facilitators regarding PV activities from the point of view of healthcare professionals (HCPs) in Lahore, Pakistan. A cross-sectional questionnaire-based survey was conducted between September 2018 to January 2019. The data was collected through convenience sampling of physicians, pharmacists, and nurses at tertiary care public hospitals in Lahore. A total of 384 questionnaires were distributed, and 346 HCPs responded to the survey. Over 62% percent of physicians and 54.8% of nurses agreed that they did not know how to report an ADR in their workplace. About 43.2% of pharmacists and 40.1% of nurses disagreed that they were not aware of the need for ADR reporting. Furthermore, 41.6% of nurses identified a lack of financial reimbursement and 51.8% highlighted a lack of support from a colleague as a reason that could lead to the underreporting of ADR. The majority of participants, including 69.6% physicians, 48.6% pharmacists, and 55.3% nurses identified the lack of knowledge about the existence of a national PV centre. Extra time for ADR reporting, incentives, continuous medical education, reminders, and availability of an online ADR reporting system was classed as the facilitators and were agreed upon by the majority of HCPs.

Assessment of Knowledge, Attitude, and Practice of Obstetricians and Gynecologists Toward Off-Label Medicine Use in Female Reproductive Health Issues.

Background: Off-label medication usage (OLMU) is prevalent in the treatment of various diseases, including female reproductive health issues (FRHIs). However, there is a paucity of literature on the perspective of health professionals on this subject. The purpose of the current study was to assess gynecologists/obstetricians' knowledge, attitude and practice toward OLMU in the treatment of FRHIs. Methods: The current cross-sectional study was conducted in September and October 2021, at five tertiary care hospitals (two public and three private sector), different clinics and maternity homes in a metropolitan city of Karachi, Pakistan. The target population was gynecologists, obstetricians and physicians/residents working in the ob/gyn department in various hospitals and clinical settings of Karachi. Results: The overall response rate was 77.1%. The mean age of the study respondents was 36.1 ± 7.7 years; n = 85 (55.9%) respondents were working in primary patient care. The majorly reported OLMU by the respondents were clomiphene citrate in unexplained infertility (n = 66; 43.4%), metformin to improve cycle regularity in females with polycystic ovary syndrome (PCOS) (n = 59; 38.8%) and letrozole to induce ovulation (n = 31; 20.4%). The majorly stated categories of OLMU were at a different dose (n = 95; 62.5%) and at different indications than approved to treat (n = 89; 58.5%). It was reported by the majority of the respondents (n = 95; 62.5%) that they do not follow any guidelines or regulations for OLMU in their work setting; however, the response was statistically varied with the working organization (CI 2.14-2.93; p = 0.037) and practice area (CI 2.85-4.32; p = 0.0001) of respondents. Conclusions: The present study revealed that the respondents were well-familiar with the practice of OLMU in the treatment of FRHIs. They expressed their concerns about decreasing such practices by being involved in collective decision-making procedures, and they were inclined to accept initiatives aimed at ensuring drug safety in patients.

Healthcare Professionals' Practice of HIV Post-Exposure Prophylaxis in Clinical Settings in Karachi, Pakistan.

The human immunodeficiency virus (HIV) is an important public health concern that has become more prevalent in Pakistan in recent decades. Healthcare professionals (HCPs) are frequently exposed to many HIV-infected patients; as a result, they are more vulnerable to HIV infection due to occupational exposure. Hence, the current study was executed to evaluate HCPs' knowledge, attitude and practice in terms of post-exposure prophylaxis (PEP) for HIV. This cross-sectional study was carried out in several clinical and laboratory settings of Karachi and the HCPs involved in treating patients were surveyed using a structured questionnaire. The Shapiro-Wilk test was performed to establish the normality of the variables. Pearson correlation was employed to identify the relationship between the independent variables considering p-values < 0.05 as statistically significant. A total of 578 filled forms were incorporated in the study with a response rate of 72.2%. Physicians and medical students (OR = 1.68; 95% CI = 1.16-2.24; p = 0.001) belonging to private work settings (OR = 1.84; 95% CI = 1.33-2.35; p < 0.003) indicated better knowledge. The majority, 407 (70.4%), of the respondents reported having been exposed to risky occupational circumstances during their professional life; however, 65.7% took PEP for HIV after exposure and only 56.8% completed the entire course. A statistically significant association was observed between experience (p = 0.004, CI = 0.14-0.72), job category (p = 0.0001, CI = 0.16-0.62) and frequency of exposure (p = 0.003, CI = 0.42-11.31) and reporting of occupational exposure. More than half (53.8%) of respondents stated that their institute has a policy for the management of HIV exposures; however, their response was significantly associated with their organization (p = 0.004). The current study shows adequate knowledge revealing a positive attitude among respondents; however, there was a gap between the knowledge and its practical application. Even though many of the HCPs had experienced risky HIV exposure, a lack of reporting was noted in the study.