The evaluation of antibiotic susceptibility pattern and associated risk factors of UTI in tertiary care hospital of Peshawar.

UTIs are majorly caused by species of bacteria in patients of almost all ages. The study was aimed to determine the prevalence rate of uropathogens, its antibiotic susceptibility pattern and associated risk factors. Urine samples were collected from n=470 participants using sterilized containers and were inoculated on culture media. The isolates were identified via gram-staining and biochemical characterization. A total of 43.20% samples were positive. Female contributed the highest prevalence rate, 78.82% as compared to male, 21.18%. The highest prevalence 40.90% was observed in the age-group 31-45, followed by 16-30 with 36.90%. Escherichia coli (47.80%) was the most prevalent, followed by Klebsiella pneumoniae (18.2%), Enterococcus faecalis (12.80%), Pseudomonas aeruginosa (10.30%) and Proteus mirabilis (7.40%). Staphylococcus aureus showed high sensitivity (100%) to amikacin, meropenem, imipenem, fosfomycin, vancomycin, clindamycin and linezolid while in case of E. faecalis, vancomycin and linezolid were highly potent. Amikacin and meropenem showed the highest (100%) potency followed by imipenem While Fosfomycin was highly potent to E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa with potency rate 89.97%, 92.31%, 100% and 100% respectively. In the current study, the positivity rate was highly observed in female. E. coli and K. pneumoniae were found the most ubiquitous for UTI.

Advancing oncology drug therapies for sub-Saharan Africa.

Cancer incidence is rising across sub-Saharan Africa (SSA), and is often characterized by late-stage presentation, early age of onset and poor survival. While a number of oncology drugs are now improving the length and quality of life for cancer patients in high-income countries, significant disparities in access to a range of oncology therapeutics exist for SSA. A number of challenges to drug access such as drug costs, lack of infrastructure and trained personnel must be urgently addressed to advance oncology therapies for SSA. We present a review of selected oncology drug therapies that are likely to benefit cancer patients with a focus on common malignancies in SSA. We collate available data from seminal clinical trials in high-income countries to highlight the potential for these therapeutics to improve cancer outcomes. In addition, we discuss the need to ensure access to drugs within the WHO Model List of Essential Medicines and highlight therapeutics that require consideration. Available and active oncology clinical trials in the region is tabulated, demonstrating the significant gaps in access to oncology drug trials across much of the region. We issue an urgent call to action to address drug access due to the predicted rise in cancer burden in the region in coming years.

Commentary on the new English smoking cessation Advanced service: a sustainable gateway to care or will it disappear in a puff of smoke?

Further to plans to make England 'smoke-free' by 2030, a new English community pharmacy smoking cessation service was launched in March 2022. The service includes offering people admitted to hospital an opportunity to enrol on a smoking cessation service that allows care to be maintained through their community pharmacy upon discharge. There is a high expectation for this service, which is expected to increase 1-year quit rates by 11% and in its first year, save the UK NHS £85 million in healthcare resources. The service also offers opportunities for pharmacists to assume a greater role in managing the long-term care of smokers. However, as with any new service, without careful monitoring of the implementation, there may be unforeseen and unintended consequences for what are otherwise well-intentioned actions. For instance, despite existing smoking cessation services being effective, historically there has always been poor smoker uptake, particularly people from less affluent backgrounds and from marginalised groups. Questions also arise about service adoption and implementation and how the risks associated with transitions between care providers will be managed. This timely commentary explores and examines these issues. Specifically, we add to the debate by focusing on the extent to which the new service caters or enables people from disadvantaged groups to participate fully. The challenges of adoption and implementation in pharmacies are discussed as well as the strategies to overcome foreseeable problems that might arise during transitions of care.

Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: The Search for the Optimal Biomarker.

Triple negative breast cancer (TNBC) is a high-risk and aggressive malignancy characterized by the absence of estrogen receptors (ER) and progesterone receptors (PR) on the surface of malignant cells, and by the lack of overexpression of human epidermal growth factor 2 (HER2). It has limited therapeutic options compared to other subtypes of breast cancer. There is now a growing body of evidence on the role of immunotherapy in TNBC, however much of the data from clinical trials is conflicting and thus, challenging for clinicians to integrate the data into clinical practice. Landmark phase III trials using immunotherapy in the early-stage neoadjuvant setting concluded that the addition of immunotherapy to chemotherapy improved the pathologic complete response (pCR) rate compared to chemotherapy with placebo while others found no significant improvement in pCR. Phase III trials have investigated the utility of immunotherapy in previously untreated metastatic TNBC, and these studies have similarly arrived at inconsistent conclusions. Some studies showed no benefit while others demonstrated a clinically significant improvement in overall survival in the PD-L1 positive population. It is not yet clear which biomarkers are most useful, and assays for these biomarkers have not been standardized. Given the often serious and severe side effects of immunotherapy, it is important and necessary to identify predictive biomarkers of response and resistance in order to enhance patient selection. In this review, we will discuss both the challenges of traditional biomarkers and the opportunities of emerging biomarkers for patient selection.

Covid-19 Mortality in an Acute Care Hospital: Association of Patient Factors With Decision to Forego the Intensive Care Unit.

BACKGROUND: Public awareness of the large mortality toll of COVID-19 particularly among elderly and frail persons is high. This public awareness represents an enhanced opportunity for early and urgent goals-of-care discussions to reduce medically ineffective care. OBJECTIVE: To assess the end-of-life experiences of hospitalized patients dying of COVID-19 with respect to identifying the clinical factors associated with utilization or non-utilization of the ICU. METHODS: Retrospective cohort study of hospital outcomes using electronic medical records and individual chart review from March 15, 2020 to October 15, 2020 of every patient with a COVID-19 diagnosis who died or was admitted to hospice while hospitalized. Logistic regression multivariate analysis was used to identify the clinical and demographic factors associated with non-utilization of the ICU. RESULTS: 133/749 (18%) of hospitalized COVID-19 patients died or were admitted to hospice as a result of COVID-19. Of the 133, 66 (49.6%) had no ICU utilization. In multivariate analysis, the significant patient factors associated with non-ICU utilization were increasing age, normal body mass index, and the presence of an advanced directive calling for limited life sustaining therapies. Race and residence at time of admission (home vs. facility) were significant only in the unadjusted analyses but not in adjusted. Gender was not significant in either form of analyses. CONCLUSION: Goals of care discussions performed by an augmented palliative care team and other bedside clinicians had renewed urgency during COVID-19. Large percentages of patients and surrogates, perhaps motivated by public awareness of poor outcomes, opted not to utilize the ICU.

Understanding the barriers and enablers of pharmacogenomic testing in primary care: a qualitative systematic review with meta-aggregation synthesis.

Introduction: Pharmacogenomic testing can indicate which drugs may have limited therapeutic action or lead to adverse effects, hence guiding rational and safe prescribing. However, in the UK and other countries, there are still significant barriers to implementation of testing in primary care. Objective: This systematic review presents the barriers and enablers to the implementation of pharmacogenomics in primary care setting. Materials & methods: MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched through to July 2020 for studies that reported primary qualitative data of primary care professionals and patient views. Following screening, data extraction and quality assessment, data synthesis was undertaken using meta-aggregation based on the theoretical domain's framework (TDF). Confidence in the synthesized findings relating to credibility and dependability was established using CONQual. Eligible papers were categorized into six TDF domains - knowledge; social and professional roles; behavioral regulation; beliefs and consequences; environmental context and resources; and social influences. Results: From 1669 citations, eighteen eligible studies were identified across seven countries, with a sample size of 504 participants including both primary care professionals and patients. From the data, 15 synthesized statements, all with moderate CONQual rating emerged. These categories range from knowledge, awareness among Primary Care Physicians and patients, professional relationships, negative impact of PGx, belief that PGx can reduce adverse drug reactions, clinical evidence, cost-effectiveness, informatics, reporting issues and social issues. Conclusion: Through use of TDF, fifteen synthesized statements provide policymakers with valuable recommendations for the implementation of pharmacogenomics in primary care. In preparation, policymakers need to consider the introduction of effective educational strategies for both PCPs and patients to raise knowledge, awareness, and engagement. The actual introduction of PGx will require reorganization with decision support tools to aid use of PGx in primary care, with a clear delegation of roles and responsibilities between general professionals and pharmacists supplemented by a local pool of experts. Furthermore, policy makers need to address the cost effectiveness of pharmacogenomics and having appropriate infrastructure supporting testing and interpretation including informatic solutions for utilizing pharmacogenomic results.

Findings From Severe Maternal Morbidity Surveillance and Review in Maryland.

Importance: In the US, more than 50 000 women experience severe maternal morbidity (SMM) each year, and the SMM rate more than doubled during the past 25 years. In response, professional organizations called for birthing facilities to routinely identify and review SMM events and identify prevention opportunities. Objective: To examine SMM levels, primary causes, and factors associated with the preventability of SMM using Maryland's SMM surveillance and review program. Design, Setting, and Participants: This cross-sectional study included pregnant and postpartum patients at 42 days or less after delivery who were hospitalized at 1 of 6 birthing hospitals in Maryland between August 1, 2020, and November 30, 2021. Hospital-based SMM surveillance was conducted through a detailed review of medical records. Exposures: Hospitalization during pregnancy or within 42 days post partum. Main Outcomes and Measures: The main outcomes were admission to an intensive care unit, having at least 4 U of red blood cells transfused, and/or having COVID-19 infection requiring inpatient hospital care. Results: A total of 192 SMM events were identified and reviewed. Patients with SMM had a mean [SD] age of 31 [6.49] years; 9 [4.7%] were Asian, 27 [14.1%] were Hispanic, 83 [43.2%] were non-Hispanic Black, and 68 [35.4%] were non-Hispanic White. Obstetric hemorrhage was the leading primary cause of SMM (83 [43.2%]), followed by COVID-19 infection (57 [29.7%]) and hypertensive disorders of pregnancy (17 [8.9%]). The SMM rate was highest among Hispanic patients (154.9 per 10 000 deliveries), primarily driven by COVID-19 infection. The rate of SMM among non-Hispanic Black patients was nearly 50% higher than for non-Hispanic White patients (119.9 vs 65.7 per 10 000 deliveries). The SMM outcome assessed could have been prevented in 61 events (31.8%). Clinician-level factors and interventions in the antepartum period were most frequently cited as potentially altering the SMM outcome. Practices that were performed well most often pertained to hospitals' readiness and adequate response to managing pregnancy complications. Recommendations for care improvement focused mainly on timely recognition and rapid response to such. Conclusions and Relevance: The findings of this cross-sectional study, which used hospital-based SMM surveillance and review beyond the mere exploration of administrative data, offers opportunities for identifying valuable quality improvement strategies to reduce SMM. Immediate strategies to reduce SMM in Maryland should target its most common causes and address factors associated with preventability identified at individual hospitals.

Specialist recommendation for chemoprevention medications in patients at familial risk of breast cancer: a cross-sectional survey in England.

In England, the National Institute for Health and Care Excellence guideline for familial breast cancer recommends chemoprevention for women at high and moderate familial risk of breast cancer. However, prescribing of chemoprevention has not improved since the introduction of the guideline in 2013. The study aims to identify the current practice, in England, of familial cancer specialists offering chemoprevention and recommending prescribing in primary care. This was an anonymized national cross-sectional survey of familial breast cancer risk services in England. Lead clinicians were sent an online survey link. The survey questions included whether chemoprevention was offered/considered for high- and moderate-risk women, when chemoprevention prescribing and recommendation to primary care started, medications prescribed, age groups considered for chemoprevention, and existence of a shared prescribing protocol with primary care. The survey was sent to 115 hospital services; responses from 50 services (43%) were included in the analysis. Of the 40 services offering chemoprevention for high-risk women, 15 (38%) did not prescribe but 31 (78%) recommended prescribing to primary care. Of the 31 services considering chemoprevention for moderate risk, eight (26%) did not prescribe with 26 (84%) recommended prescribing to primary care. Only three services reported having a shared protocol with primary care. Within 3 years of the guidelines, many services recognized the role of chemoprevention for both high and moderate risk with a key role for primary care to initiate prescribing. However, there is still room for improvement.

Clinical and Pharmacologic Differences of CDK4/6 Inhibitors in Breast Cancer.

Targeted therapies such as Cyclin Dependent Kinase 4 and 6 (CDK 4/6) inhibitors have improved the prognosis of metastatic hormone receptor (HR) positive breast cancer by combating the resistance seen with traditional endocrine therapy. The three approved agents currently in the market are palbociclib, ribociclib and abemaciclib. Besides the overall similarities associated with CDK4/6 inhibition, there are differences between the three approved agents that may explain the differences noted in unique clinical scenarios- monotherapy, patients with brain metastases or use in the adjuvant setting. This review article will explore the preclinical and pharmacological differences between the three agents and help understand the benefits seen with these agents in certain subgroups of patients with metastatic HR positive breast cancer.

Risk factors for severe illness in hospitalized Covid-19 patients at a regional hospital.

BACKGROUND: The Covid-19 pandemic threatens to overwhelm scarce clinical resources. Risk factors for severe illness must be identified to make efficient resource allocations. OBJECTIVE: To evaluate risk factors for severe illness. DESIGN: Retrospective, observational case series. SETTING: Single-institution. PARTICIPANTS: First 117 consecutive patients hospitalized for Covid-19 from March 1 to April 12, 2020. EXPOSURE: None. MAIN OUTCOMES AND MEASURES: Intensive care unit admission or death. RESULTS: In-hospital mortality was 24.8% and average total length of stay was 11.82 days (95% CI: 10.01 to 13.63 days). 30.8% of patients required intensive care unit admission and 29.1% required mechanical ventilation. Multivariate regression identified the amount of supplemental oxygen required at admission (OR: 1.208, 95% CI: 1.011-1.443, p = .037), sputum production (OR: 6.734, 95% CI: 1.630-27.812, p = .008), insulin dependent diabetes mellitus (OR: 11.873, 95% CI: 2.218-63.555, p = .004) and chronic kidney disease (OR: 4.793, 95% CI: 1.528-15.037, p = .007) as significant risk factors for intensive care unit admission or death. Of the 48 patients who were admitted to the intensive care unit or died, this occurred within 3 days of arrival in 42%, within 6 days in 71%, and within 9 days in 88% of patients. CONCLUSIONS: At our regional medical center, patients with Covid-19 had an average length of stay just under 12 days, required ICU care in 31% of cases, and had a 25% mortality rate. Patients with increased sputum production and higher supplemental oxygen requirements at admission, and insulin dependent diabetes or chronic kidney disease may be at increased risk for severe illness. A model for predicting intensive care unit admission or death with excellent discrimination was created that may aid in treatment decisions and resource allocation. Early identification of patients at increased risk for severe illness may lead to improved outcomes in patients hospitalized with Covid-19.

Radiofrequency radiations induced genotoxic and carcinogenic effects on chickpea (Cicer arietinum L.) root tip cells.

Present study was under taken to predict the possible DNA damages (genotoxicity) and carcinogenicity caused by radiofrequency radiations (RF) to living tissue. Dry seeds of chickpea were treated with GSM cell phone (900 MHz) and laptop (3.31 GHz) as RF source for 24 and 48 h. Untreated seeds were used as (0 h) negative control and Gamma rays (250 Gray) as positive control. Plant chromosomal aberration assay was used as genotoxicity marker. All the treatment of RF inhibits seed germination percentage. 48 h laptop treatment has the most negative effect as compared to untreated control. A decrease was observed in mitotic index (M.I) and increase in abnormality index (A.I) with the increase in exposure duration and frequency in (Hz). Cell membrane damages were also observed only in 48 h exposure of cell phone and laptop (RF). Maximum nuclear membrane damages and ghost cells were again recorded in 48 h exposure of cell phone and laptop. The radiofrequency radiations (900 MHz and 3.31 GHz) are only genotoxic as they induce micronuclei, bi-nuclei, multi-nuclei and scattered nuclei but could be carcinogenic as 48 h incubation of RF induced fragmentation and ghost cells. Therefore cell phones and laptop should not be used unnecessarily to avoid possible genotoxic and carcinogenic effects.