Recent developments in targeting breast cancer stem cells (BCSCs): a descriptive review of therapeutic strategies and emerging therapies.

Despite recent advancements in the diagnosis and treatment of breast cancer (BC), patient outcomes in terms of survival, recurrence, and disease progression remain suboptimal. A significant factor contributing to these challenges is the cellular heterogeneity within BC, particularly the presence of breast cancer stem cells (BCSCs). These cells are thought to serve as the clonogenic nexus for new tumor growth, owing to their hierarchical organization within the tumor. This descriptive review focuses on the evolving strategies to target BCSCs, which have become a pivotal aspect of therapeutic development. We explore a variety of approaches, including targeting specific tumor surface markers (CD133 and CD44), transporters, heat shock proteins, and critical signaling pathways like Notch, Akt, Hedgehog, KLF4, and Wnt/ß-catenin. Additionally, we discuss the modulation of the tumor microenvironment through the CXCR-12/CXCR4 axis, manipulation of pH levels, and targeting hypoxia-inducible factors, vascular endothelial growth factor, and CXCR1/2 receptors. Further, this review focuses on the roles of microRNA expression, strategies to induce apoptosis and differentiation in BCSCs, dietary interventions, dendritic cell vaccination, oncolytic viruses, nanotechnology, immunotherapy, and gene therapy. We particularly focused on studies reporting identification of BCSCs, their unique properties and the efficacy of various therapeutic modalities in targeting these cells. By dissecting these approaches, we aim to provide insights into the complex landscape of BC treatment and the potential pathways for improving patient outcomes through targeted BCSC therapies.

Predictors of mortality among hospitalized hypertensive patients with COVID-19 during third and fourth waves in Pakistan.

INTRODUCTION: Hypertension significantly contributes to the severity and mortality of COVID-19 patients. It has also been a risk factor for prolonged hospitalization and the need for intensive care. However, the data is still evolving. Therefore, this study investigated the predictors of mortality among hypertensive COVID-19 patients. METHODOLOGY: A single-center cohort study was performed at Indus Hospital and Health Network, Karachi, Pakistan, between April 1, 2021, and October 31, 2021. This study included 333 hospitalized hypertensive COVID-19 patients and evaluated their clinical characteristics and survival outcomes. A multivariate logistic regression model was applied in IBM SPSS 27.0 to determine the predictors of mortality. RESULTS: The majority of patients were females (54.7%), the median age was 62 [55-70] years, with co-existing diabetes (56.5%) and severely ill (52.6%). The independent predictors of mortality identified were age ≥ 65 years (aOR 20.89, 95% CI, 5.81-75.15; p < 0.001), pulse rate (aOR 1.03, 95% CI 1.01-1.63; p = 0.006), serum creatinine (aOR 1.34, 95% CI 1.11-1.63; p = 0.002), use of antibiotics (aOR 3.40, 95% CI 1.29-8.98; p = 0.014)), corticosteroid (aOR 49.68, 95% CI 1.83-1350.31; p = 0.020), and who needed high flow oxygen supply (aOR 13.08, 95% CI 1.70-100.54; p < 0.001), non-invasive mechanical ventilation (aOR 229.01, 95% CI 29.30-1789.71; p < 0.001) and invasive mechanical ventilation (aOR 379.54, 95% CI 36.60-3935.87; p < 0.001). CONCLUSIONS: Our study suggests that older age, elevated pulse rate, serum creatinine, use of antibiotics and corticosteroids, and the need for mechanical ventilation predict mortality among hypertensive COVID-19.

Non-prescription antibiotics dispensing by community pharmacies: implications for antimicrobial resistance.

Introduction: The non-prescription antibiotics dispensing (NPAD) from pharmacies is on the rise in low- and middle-income countries, which contributes to the emergence of antimicrobial resistance (AMR). This study was conducted with the objective to determine the community pharmacy personnel's perspectives on NPAD and its implications for AMR. Methods: A questionnaire-based cross-sectional survey was conducted in Pakistan among 336 pharmacies. The data were analyzed using SPSS v21 and MedCalc for Windows v12.3.0. Modified Bloom's cut-off point was utilized to categorize the participants' overall knowledge, attitude, and practice. For univariable logistic regression analyses, odds ratio (OR) was calculated at 95% confidence interval (CI). For multivariable logistic regression analyses, adjusted OR was calculated at 95% CI. Spearman's rank correlation coefficient test was used to assess the relationships among knowledge, attitude, and/or practice scores. Results: The majority of the respondents were staff pharmacists (45.5%). About four-fifths (78.9%) and half (50.9%) of the participants demonstrated moderate to good knowledge and practice, respectively. However, about only one-third (33.1%) had a moderate to good attitude. Staff pharmacists had higher odds of moderate to good knowledge (OR: 2.4, 95% CI: 1.2-4.7) and practice (OR: 2.3, 95% CI: 1.4-3.8). Total knowledge and practice (Spearman's ρ: 0.280; P <0.001) and total attitude and practice (Spearman's ρ: 0.299; P <0.001) scores were significantly correlated. Conclusion: The qualified pharmacists had satisfactory knowledge, attitude, and practices toward antibiotics. However, non-pharmacist staff lacked knowledge and had probable NPAD practice, which has a negative impact on public health. Regular refresher training, seminars, and strict enforcement of rules and regulations are essential.

Qualitative exploration of perspectives of the pharmacists working in public-sector hospitals during COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic, a serious global health threat, has excruciating social and economic implications given its transmissibility, lack of therapy, and severity. In such a situation, pharmacists as frontline healthcare professionals hold a significant position to tackle. This study was designed to explore the perception and preparedness of pharmacists working in public sector hospitals amid such a pandemic in Pakistan. METHODS: A total of 11 pharmacists were interviewed for this qualitative study design through a semi-structured interview guide. The interviews were recorded and transcribed verbatim. RESULTS: The thematic content analysis yielded six major themes; understanding of COVID-19, perceptions towards COVID-19, preventive aspects, management aspects, changes to lifestyle, and psychological aspects. Though efficient preparedness and approach to fighting against such pandemics were reported, pharmacists were found susceptible to infection and psychological stress. They also expressed lockdown as an effective measure to prevent the disease from spreading but still were concerned about its economic and social impact. CONCLUSIONS: Adequate planning and facilities from the national level should be made available for strengthening the hospital pharmacy service that helps improve the overall healthcare system of low- and middle-income countries like Pakistan. The provision of a protective facility, incentives, and occupational health surveillance packages are deemed necessary to boost the self-esteem and morale of hospital pharmacists that safeguard the early and effective management of such disasters.

A national survey to assess breast cancer awareness among the female university students of Pakistan.

The incidence of breast cancer is increasing in Pakistan as well as globally. Awareness of women about breast cancer plays a cornerstone role in its early detection, better management, and prevention. Keeping this in mind, a cross-sectional study was carried out to assess the awareness of female university students about breast cancer's risk factors, signs and symptoms, and breast cancer examination. The data was collected from female university students studying in Pakistan. A total of 774 participants completed the survey and recorded their responses on an online pre-tested self-administered questionnaire. Only 29.8% of the participants have identified breast cancer history in their first-degree relatives as a risk factor. Moreover, 14.1% of the participant considered that the use of oral contraceptives for more than 5 years can increase the risk of developing breast cancer. In addition, inward pulled nipple, wounds around the nipple, and abrupt changes in the breast size were considered as the sign and symptoms of breast cancer by 25.2%, 25.7%, and 31.7% of the participants, respectively. Moreover, only 20.9% of the participants identified the correct year for starting breast cancer examination and 44.4% of the respondents marked that mammography should be initiated after 40 years. Overall, the university female students of Pakistan were poorly aware of breast cancer's risk factors, signs and symptoms, and breast examination. This study has highlighted the need for initiation of aggressive strategies regarding breast cancer awareness in both the literate and illiterate female population of Pakistan.

Assessing Barriers Faced by Surgeons While Providing Surgical Care During the COVID-19 Pandemic in Pakistan: An Online Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic is not only affecting public health, but it is also impairing the specialized surgical care services in the hospitals. The present study aimed to assess the barriers faced by the surgeons while performing surgical procedures during the COVID-19 pandemic. METHODS: A cross-sectional, web-based survey was conducted from September 10 to October 14, 2020. The study population consisted of surgeons practicing in Kpk, Pakistan. Descriptive statistics and binary logistic regression analysis were used to analyze the data. RESULTS: A total of 292, out of 543, surgeons participated in the study (response rate: 59.6%). The younger surgeons (25-30 years) considered the lack of policies and practices regarding exposure to COVID-19 patients as a significant barrier to their practice. The surgeons practicing in private hospitals considered themselves at a higher risk while providing surgical care to the COVID-19 patients. The non-cooperation of the patients was the main barrier in delivering surgical care services. CONCLUSION AND RECOMMENDATION: The current study highlighted the barriers to the surgeons while providing surgical care to patients in the current pandemic. The most pronounced barriers to the surgeons were the lack of policies regarding exposure to COVID-19 and practice and non-cooperation of the patient. To address these barriers, it is recommended that health regulatory agencies of Pakistan should implement strict infection control practices to ensure the safety of surgeons and allied healthcare staff during the COVID-19 pandemic.

The Impact of Treatment Adherence on Quality of Life Among Type 2 Diabetes Mellitus Patients - Findings from a Cross-Sectional Study.

AIM: The current study was conducted to assess the factors contributing to treatment adherence and its impact on the quality of life (QoL) in type 2 diabetes mellitus (T2DM) patients. METHODS: A cross-sectional study was conducted between January 2020 to March 2020 among T2DM patients. The data was collected from T2DM out-patient clinics. The participants were recruited by using a simple random sampling method. To assess the association of demographics with the level of adherence, binary logistics regression analysis was applied. Moreover, the Mann-Whitney U-test was used to evaluate the impact of adherence on QoL. RESULTS: A total of 384 patients participated in this study. Amongst them, 60.2% were male and 39.8% were female. Low adherence was seen in illiterate patients and patients older than 40 years. The results showed that good QoL in T2DM patients was significantly associated with treatment adherence (p= 0.004). CONCLUSION: The finding of the current study showed that the non-adherence prevailed in illiterate strata of the study population and the medication adherence significantly affects the QoL in T2DM patients. These findings suggest that health regulatory agencies should focus on implementing disease-education interventions for improving the adherence to medications in patients with long-term conditions.

Knowledge, Attitude, and Practices Toward COVID-19 in Primary Healthcare Providers: A Cross-Sectional Study from Three Tertiary Care Hospitals of Peshawar, Pakistan.

An online cross-sectional study was carried out to evaluate the knowledge, attitude, and practice about coronavirus disease 2019 (COVID-19) among primary health care providers (PHPs) at three tertiary care hospital, Peshawar, Pakistan. Data was collected via email and online social media platforms. Statistical package for social science (SPSS) version 25.0 was used for data analysis. Among the total participants (n = 114), 74 (66.7%) were male and 37 (33.3%) were female. The mean scores for knowledge, attitude and practice were 12.7 ± 0.89, 8.9 ± 4.1 and 7.3 ± 1.2, respectively. Most of the participants knew the term COVID-19 and its mode of transmission (90%), signs and symptoms (84%) and risk factors (72%) associated with it. Most of the participants agreed that COVID-19 can be transmitted through coughing and sneezing (74.3%) and 84.6% were in favor that COVID-19 can be prevented by adopting preventive measures. Around 68.8% of the participants disagreed with the use of antibiotics in the prevention of COVID-19. Ninety percent of the respondents were avoiding close contact with the people having cough and flu-like symptoms. Most PHPs had good knowledge, positive attitude and reasonable practices regarding COVID-19. Moreover, focused training programs for PHPs at the Government level can further improve their understanding of risks and preventive strategies related to COVID-19, which will help them to provide appropriate care to their patients as well as to protect themselves from this infection.

A national study to assess pharmacists' preparedness against COVID-19 during its rapid rise period in Pakistan.

To evaluate the pharmacist's preparedness against the COVID-19 during its rapid rise period in Pakistan, an online cross-sectional study was carried out from March 30 to May 22, 2020 among the pharmacists using a pre-validated self-administered questionnaire. A total of 1149 participants completed the survey, amongst which 430(37.9%) were working as retail pharmacists, 216 (18.8%) as community pharmacists, and 213(18.5%) as hospital pharmacists. The mean COVID-19 knowledge score of the participants was 6.77±0.5, which indicated that 84% of them had good knowledge about COVID-19. The multiple linear regression model revealed that attitude was significantly associated with gender (p = 0.001), marital status (p<0.0001) and resident (p = 0.013). The mean practice score was 2.85±0.4, showing that 94% of the participants were following adequate preventive practices against this infection. The results from this study suggest that Pharmacists demonstrated good knowledge, positive attitudes, and acceptable practices regarding COVID-19.

Assessing the Impact of COVID-19 on the Mental Health of Healthcare Workers in Three Metropolitan Cities of Pakistan.

PURPOSE: The COVID-19 (coronavirus disease-2019) has been associated with psychological distress during its rapid rise period in Pakistan. The present study aimed to assess the mental health of healthcare workers (HCWs) in the three metropolitan cities of Pakistan. METHODS: A cross-sectional, web-based study was conducted in 276 HCWs from April 10, 2020, to June 5, 2020. Depression, anxiety, and stress scale (DASS-21) were used for the mental health assessment of the HCWs. Multivariable logistic regression analysis (MLRA) was performed to measure the association between the demographics and the occurrence of depression, anxiety, and stress (DAS). RESULTS: The frequency of DAS in the HCWs was 10.1%, 25.4%, and 7.3%, respectively. The MLRA showed that the depression in HCWs was significantly associated with the profession (P<0.001). The anxiety in HCWs was significantly associated with their age (P=0.005), profession (P<0.05), and residence (P<0.05). The stress in HCWs was significantly associated with their age (P<0.05). LIMITATION: This study was conducted in the early phase of the COVID-19 pandemic, when the number of COVID-19 cases was on the rise in Pakistan and it only represents a definite period (April to June 2020). CONCLUSION: The symptoms of DAS are present in the HCWs of Pakistan and to manage the psychological health of HCWs, there is a need for the initiation of psychological well-being programs.

Religious Cliché and Stigma: A Brief Response to Overlooked Barriers in COVID-19 Management.

For decades, religion has provided explanations and answers to existential questions and queries that can emerge during a pandemic. This characteristic of religion has helped communities in finding answers and meanings to their confusions. During a pandemic, healthcare professionals are often unprepared in answering the patients' religious beliefs regarding the diseases. Moreover, patients are faced with religious clichés and stigma that results because of religious beliefs and practices. To overcome the religious stigma, a deeper understanding of religious beliefs and values is required so that a perception or practice change can take place. Therefore, the inclusion and collaboration of spiritual leaders with healthcare professionals are needed to ensure a holistic understanding and overcome the stigma that can shape as a barrier for reaching an optimal therapeutic outcome.

Patterns of physicians' knowledge, attitude and prescribing trends against upper respiratory tract infections in Lahore, Pakistan.

Although viruses cause most of upper respiratory tract infections but still antibiotics are irrationally prescribed in mild infections, especially in upper respiratory tract infections. To identify gaps among prescribers, due to lack of standard guidelines and antimicrobial stewardship programs, it is needed to check knowledge, attitude, perception and current prescribing pattern of antibiotics. Based on the data recommendations can be specified to overcome the prescribing deficiencies and increasing rates of antimicrobial resistance. It is inevitable to educate patients about ineffectiveness of antibiotics in viral infections, and to develop guidelines for prescribing antibiotics, running continuing medical education and establishing antibiotic stewardship programs. We conducted a cross-sectional survey-based study by engaging physicians of public and private sector hospitals in Lahore, Pakistan. About 66% agreed for semi-structured interview and met the inclusion criteria. Fifty percent of physicians have an understanding that antibiotics should be prescribed in URTIs, otherwise symptoms may get worsen. The only encouraging thing is that 78.8% believe that antibiotics are being misused and are major cause of increasing rate of resistance. Most of prescribers have an understanding that antibiotics should be prescribed in upper respiratory tract infections. They are prescribing antibiotics ignoring Center for Disease Control guidelines for the treatment or prophylaxis of upper respiratory infections.

Metabolomics and marker-based stability studies of methanol extract of seeds of Syzygium cumini L.

Though, herbal medicines are prone to deterioration upon storage due to their complex nature, but less attention has been paid to investigating stability of such products to assign shelf-life. Therefore, the present study aimed to assess the accelerated stability of methanolic extract of seeds of Syzygium cumini. The extract was kept at three different storage conditions (30oC/60% RH, 40oC/75% RH and 60oC/85% RH) for a period of 6 months. The samples withdrawn at 0 (before starting the study), 1, 2, 3, 4 and 6 months were analyzed to get UV-Visible metabolomics fingerprints and determine caffeic acid contents using RP-HPLC. The comparison of metabolomics fingerprints indicated that the extract was stable for 1 month at all the three storage conditions. However, caffeic acid contents were found to be intact for a longer period of time. Following the zero order degradation, caffeic acid was predicted to be stable for more than 3 years, if kept at 25oC. The results of the present study indicate that metabolomes of methanol extract of seeds of Syzygium cumini change very fast, suggesting the development of stable formulations.

A qualitative study exploring perceptions and attitudes of community pharmacists about extended pharmacy services in Lahore, Pakistan.

BACKGROUND: In recent decades, community pharmacies reported a change of business model, whereby a shift from traditional services to the provision of extended roles was observed. However, such delivery of extended pharmacy services (EPS) is reported from the developed world, and there is scarcity of information from the developing nations. Within this context, the present study was aimed to explore knowledge, perception and attitude of community pharmacists (CPs) about EPS and their readiness and acceptance for practice change in the city of Lahore, Pakistan. METHODS: A qualitative approach was used to gain an in-depth knowledge of the issues. By using a semi-structured interview guide, 12 CPs practicing in the city of Lahore, Pakistan were conveniently selected. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. RESULTS: Thematic content analysis yielded five major themes. (1) Familiarity with EPS, (2) current practice of EPS, (3) training needed to provide EPS, (4) acceptance of EPS and (5) barriers toward EPS. Majority of the CPs were unaware of EPS and only a handful had the concept of extended services. Although majority of our study respondents were unaware of pharmaceutical care, they were ready to accept practice change if provided with the required skills and training. Lack of personal knowledge, poor public awareness, inadequate physician-pharmacist collaboration and deprived salary structures were reported as barriers towards the provision of EPS at the practice settings. CONCLUSION: Although the study reported poor awareness towards EPS, the findings indicated a number of key themes that can be used in establishing the concept of EPS in Pakistan. Over all, CPs reported a positive attitude toward practice change provided to the support and facilitation of health and community based agencies in Pakistan.