Evaluating the clinical benefit of pembrolizumab as a first-line agent in advanced solid tumors: A comprehensive review.

INTRODUCTION: The study evaluates the first-line application of pembrolizumab in metastatic non-small-cell lung cancer (mNSCLC), head and neck squamous cell cancer (HNSCC), gastric cancer, and renal cell carcinoma. Utilizing the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework (ASCO-VF), the analysis incorporates data from pivotal KEYNOTE trials. METHODS: The study systematically assessed the clinical benefit of pembrolizumab in advanced solid malignancies through nine randomized controlled trials, one of which comprised two experimental arms. Data extraction from primary sources was conducted from PubMed, ASCO, and ESMO publications. Utilizing ESMO-MCBS and ASCO-VF forms, the evaluation focused on clinical benefit, toxicity, and bonus points, with discrepancies resolved through consensus discussions. RESULTS: Nine first-line indications for pembrolizumab received Food and Drug Administration approval for metastatic solid tumors between 2018 and 2023. Notable distinctions in ESMO-MCBS grades revealed seven trials with substantial clinical benefit (grades 5 to 4) and three with moderate to negligible benefit (grades 3 to 1). Bonus points, primarily based on the tail of the curve, were allocated to three trials for overall survival, one for progression-free survival, and one for a significant improvement in quality of life. CONCLUSIONS: Our evaluation of pembrolizumab across diverse cancers, especially in mNSCLC and HNSCC, revealed varied outcomes and challenges in clinical benefit interpretation. The assessment of clinical benefit, incorporating quantitative and qualitative endpoints, underscores the need to consider survivorship outcomes and patient perspectives for a comprehensive understanding.

Tumour Infiltrating Lymphocytes (TILs) and immune composition in breast cancer patients from Kenya: Spatial distributions and associations with risk factors and tumour characteristics.

BACKGROUND: The immune landscape of breast cancer (BC) in patients from Sub Saharan Africa is understudied. Our aims were to describe the distribution of Tumour Infiltrating Lymphocytes (TILs) within the intratumoural stroma (sTILs) and the leading/invasive edge stroma (LE-TILs), and to evaluate TILs across BC subtypes with established risk factors and clinical characteristics in Kenyan women. METHODS: Visual quantification of sTILs and LE-TILs were performed on Haematoxylin and eosin -stained pathologically confirmed BC cases based on the International TIL working group guidelines. Tissue Microarrays were constructed and stained with immunohistochemistry (IHC) for CD3, CD4, CD8, CD68, CD20, and FOXP3. Linear and logistic regression models were used to assess associations between risk factors and tumour features with IHC markers and total TILs, after adjusting for other covariates. RESULTS: A total of 226 invasive BC cases were included. Overall, LE-TIL (mean = 27.9, SD = 24.5) proportions were significantly higher than sTIL (mean = 13.5, SD = 15.8). Both sTILs and LE- TILs were predominantly composed of CD3, CD8, and CD68. We found higher TILs to be associated with high KI67/high grade and aggressive tumour subtypes, although these associations varied by TIL locations. Older age at menarche (≥ 15 vs. < 15 years) was associated with higher CD3 (OR: 2.06, 95%CI:1.26-3.37), but only for the intra-tumour stroma. CONCLUSION: The TIL enrichment in more aggressive BCs is similar to previously published data in other populations. The distinct associations of sTIL/LE-TIL measures with most examined factors highlight the importance of spatial TIL evaluations in future studies.

The COVID-19 Pandemic and Coronary Heart Disease: the Next Surge.

PURPOSE OF REVIEW: In this narrative review, we highlight different ways in which the COVID-19 pandemic has impacted coronary heart disease (CHD) burden and how a surge in morbidity and mortality may be expected in the near future. We also discuss potential solutions, and the direction subsequent research and corrective actions should take. RECENT FINDINGS: COVID-19 has been implicated in the development and worsening of CHD via acute and chronic mechanisms in the form of plaque rupture, destabilization, and sustenance of a chronic inflammatory state leading to long COVID syndrome and increased rates of myocardial infarction. However, indirectly the pandemic is likely to further escalate the CHD burden through poor health behaviors such as tobacco consumption, reduced physical activity, economic devastation and its associated sequelae, and regular cardiac care interruptions and delays. COVID-19 has increased the total CHD burden and will require extensive resource allocation and multifaceted strategies to curb future rise.

COVID-19 and early puberty-An unintended consequence of COVID-19 lockdown?

The novel coronavirus (SARS-CoV-2) causes the disease COVID-19, also termed as acute atypical pneumonia leading to respiratory failure. Children were more likely to spend time at home due to the lockdown mandated by governments as a preventive measure, which led to alterations in dietary habits and sleeping patterns which could have had a substantial influence on their sexual development, including but not limited to faster onset of puberty. Existing data suggested a plausible relationship between COVID-19 and early puberty. Obesity, physical activity, mental health, and birth weight are major risk factors that have further contributed to the early onset of puberty. In order to address such health crises affecting children, comprehensive solutions are urgently required. As COVID-19 continues to have multiple unpredictable health consequences, spreading awareness regarding this specific problem is of paramount importance.

Supporting Kenyan women with advanced breast cancer through a network and assessing their needs and quality of life.

INTRODUCTION: Metastatic breast cancer (MBC) patients have several unmet needs. The needs and quality of life of MBC women living in sub-Saharan Africa (SSA) are understudied. Facilitating the interaction of various caregivers is beneficial in addressing the needs. Internet-based resources play an important role in reaching out to these patients. We aimed to bring the various stakeholders into a joint network force, create a web-based portal, understand the needs of MBC patients, and assess the utilization of web-based resources for women from Kenya. METHODS: A network of various stakeholders considered crucial in the care of Kenyan women with MBC was created. We conducted educational camps and assessed their needs, quality of life (QoL), and knowledge. We assessed the impact of utilizing web-based resources by MBC patients from here. RESULTS: We formed a network involving partners and launched the first dedicated website for MBC from Kenya. The website has received 13,944 visits and 310,379 hits in 2 years. One hundred fourteen women living with MBC were interviewed, and our findings show that psychological needs (63%), physical support needs (60%), and health care system needs (55%) are leading areas of needs that increase with rural residence (p = 0.001), less education (p = 0.003), and aggressive treatments (p = 0.008). Quality of life (QoL) confirmed better scores with urban residence (p = 0.002), internet access (p = 0.010), and stable disease (p = 0.042). CONCLUSIONS: Creating a network of caregivers provides opportunities for cohesive efforts in understanding the psychosocial and medical needs of patients with MBC. Internet-based resources are an effective way of reaching out to them. Kenyan patients show extremely good uptake of internet-based resources.

Knowledge, attitude, and practice regarding treatment of group a beta haemolytic tonsillo pharyngitis and prevention of rheumatic fever among doctors in Karachi, Pakistan: A perspective study.

OBJECTIVE: To assess knowledge and practices associated with rheumatic fever among medical practitioners in an urban setting. METHODS: The cross-sectional study was conducted at five major hospitals in Karachi from August to November 2019, and comprised house officers, postgraduate trainees, and general physicians of either gender. The subjects were given a questionnaire assessing their knowledge and perception regarding acute rheumatic fever as well as prophylaxis. Data was analysed using SPSS 25. RESULTS: Of the 247 respondents, 173(70%) were house officers, 31(13%) were postgraduate trainees and 43(17%) were general physicians. Overall, 202(82%) subjects were associated with some teaching hospital. Significantly more postgraduate trainees and general physicians answered correctly when asked to identify clinical and laboratory findings suggestive of Group A streptococcal throat infection than house officers (p<0.001). Among the house officers 49(28.3%), and among the postgraduate trainees 11(35.4%) knew the correct way to prescribe penicillin to prevent rheumatic fever. Among the general physicians, 20(46.5%) had accurate knowledge regarding the prescription. CONCLUSIONS: Knowledge and practices of medical practitioners regarding rheumatic fever were less than ideal and may play a part in misdiagnoses of Group A streptococcal infections and, hence, prophylaxis.

Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.

BACKGROUND: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. METHODS: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. RESULTS: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. CONCLUSIONS: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.

Role of C- reactive proteins and liver function tests in assessing the severity of dengue fever.

OBJECTIVE: To determine whether C-reactive protein and liver function tests can serve as severity markers for dengue fever. METHODS: The cross-sectional study was conducted in 2015-16 in Karachi and comprised patients with dengue fever visiting a tertiary care hospital. World Health Organisation classifications 1997 and 2009 were used to categorise patients according to clinical signs and symptoms. Receiver Operating Characteristics curve was used to determine discriminative ability and optimum cut-off value of biochemical markers. Comparisons were done through one-way analysis of variance using SPSS 17. RESULTS: Of the 218 patients, 133(61%) were males and 85(39%) were females. The overall mean age was 35.07±15.96 years. Levels of C-reactive protein and total bilirubin were significantly higher for dengue haemorrhagic fever compared to dengue fever; dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly higher for dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of C-reactive protein, total bilirubin, alanine aminotransferase and alkaline phosphatise in patients with severe dengue were significantly higher compared to non-severe dengue. CONCLUSIONS: C-reactive protein and liver function tests were found to be effective biochemical markers in assessing dengue fever severity.

Perception and practices regarding cannabis consumption in Karachi, Pakistan: A cross-sectional study.

Several studies have been carried out regarding the awareness and usage of cannabis around the world, especially in developed countries. Pakistan ranks amongst the top nations in regards to cannabis consumption. However, the amount of literature shedding light on people's perception, knowledge and practices are scarce. Therefore, the authors sought to establish a baseline study to ignite the discussion on the possibility of cannabis' induction in the medical field in Pakistan, and additionally provide a foundation for further research. The purpose of this study was to investigate the level of understanding and consumption practices in Karachi with respondents from different socio-economic backgrounds, age groups and gender regarding cannabis use and assessing the awareness of the general population. The null hypothesis is that the usage of cannabis does not have a significant correlation with age, gender, or socio-economic status of a population. We conducted a cross-sectional study in November 2018 using convenience sampling and interviewed 518 individuals for their gender, age, and socio-economic status, to determine their knowledge, attitudes, and practices regarding cannabis usage. The participants were questioned about their knowledge and its source. Attitudes were judged using three and five-point Likert scales while questions regarding practices centered upon the past and current usage of cannabis. One-way analysis of variance and chi-square tests were used as the primary statistical tests. Out of the 518 people who responded, more than half of the respondents were males (n = 340, 65.6%). The majority was familiar with the use of cannabis (n = 514, 99.2%), and the different ways in which it is consumed (n = 435, 84%). About one-third of the participants happened to consume cannabis (n = 168, 32.4%), and a quarter mentioned recreational use/curiosity as the principal reason (n = 134, 25.9%). Majority of the respondents agreed upon the harmful effects of consuming cannabis (n = 364, 70.3%), while when compared to other inimical drugs, half of them believed it to be less harmful (n = 259, 50%). Besides, an overwhelming majority stated, that if they were to consume cannabis, they would not consider taking permission from their parents/guardians (n = 441, 85.2%). Concerning legality, three-fifths of the participants chose cannabis to remain illegal in Pakistan (n = 307, 59.3%) and, for not consuming/quitting cannabis, the primary reason chosen was its harmful consequences (n = 210, 40.5%). Our study revealed that knowledge about usage of cannabis still requires a great deal of attention. Only individuals from higher socio-economic backgrounds have a positive attitude towards cannabis usage and are aware of it. There is an urgent need for awareness programs that especially reach out to the lower socio-economic status population, who otherwise do not have access to essential information resources. We also found that males were more likely to be consumers and to have more knowledge about cannabis, therefore, it is equally important to educate females about this topic so that an informed discussion about cannabis use and its medical benefits can be generated in Pakistan.

Contribution of individual components to composite end points in contemporary cardiovascular randomized controlled trials.

Cardiovascular randomized controlled trials (RCTs) typically set composite end points as the primary outcome to enhance statistical power. However, influence of individual component end points on overall composite outcomes remains understudied. METHODS: We searched MEDLINE for RCTs published in 6 high-impact journals (The Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. Two-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction, heart failure, and stroke were deemed "hard" end points, whereas hospitalization, angina, and revascularization were identified as "soft" end points. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria. RESULTS: Of the 45.8% (316/689) cardiovascular RCTs which used a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%) followed by myocardial infarction (66.1%). About 80% of the trials reported complete data for each component. One hundred forty-seven trials (46.5%) incorporated a "soft" end point as part of their composite. Death contributed the least to the estimate of effects (R2 change = 0.005) of the composite, whereas revascularization contributed the most (R2 change = 0.423). CONCLUSIONS: Cardiovascular RCTs frequently use composite end points, which include "soft" end points, as components in nearly 50% of studies. Higher event rates in composite end points may create a misleading interpretation of treatment impact due to large contributions from end points with less clinical significance.

Ethnicity and breast cancer characteristics in Kenya.

PURPOSE: There are no published data from specific regions of sub-Saharan Africa describing the clinical and pathological characteristics and molecular subtypes of invasive breast cancer by ethnic group. The purpose of this study was to investigate these characteristics among the three major ethno-cultural groupings in Kenya. METHODS: The study included women with pathologically confirmed breast cancer diagnosed between March 2012 and May 2015 at 11 hospitals throughout Kenya. Sociodemographic, clinical, and reproductive data were collected by questionnaire, and pathology review and immunohistochemistry were performed centrally. RESULTS: The 846 cases included 661 Bantus (78.1%), 143 Nilotes (16.9%), 19 Cushites (2.3%), and 23 patients of mixed ethnicity (2.7%). In analyses comparing the two major ethnic groups, Bantus were more educated, more overweight, had an older age at first birth, and had a younger age at menopause than Nilotes (p < 0.05 for all comparisons). In analyses restricted to definitive surgery specimens, there were no statistically significant differences in tumor characteristics or molecular subtypes by ethnicity, although the Nilote tumors tended to be larger (OR for ≥ 5 cm vs. < 2 cm: 3.86, 95% CI 0.77, 19.30) and were somewhat more likely to be HER2 enriched (OR for HER2 enriched vs. Luminal A/B: 1.41, 95% CI 0.79, 2.49). CONCLUSION: This case series showed no significant differences in breast cancer tumor characteristics or molecular subtypes, but significant differences in sociodemographic characteristics and reproductive factors, among the three major ethnic groups in Kenya. We suggest further evaluation of ethnic differences in breast cancer throughout the genetically and culturally diverse populations of sub-Saharan Africa.

Factors that influence advance directives completion amongst terminally ill patients at a tertiary hospital in Kenya.

BACKGROUND: An advance directive (AD) is a written or verbal document that legally stipulates a person's health care preference while they are competent to make decisions for themselves and is used to guide decisions on life-sustaining treatment in the event that they become incapacitated. AD can take the form of a living will, a limitation of care document, a do-not-resuscitate order, or an appointment of a surrogate by durable power of attorney. The completion rate of AD varies from region to region, and it is influenced by multiple factors. The objectives of this study were to determine the proportion of terminally ill patients with AD and to identify the factors that influence the completion of AD amongst terminally ill patients at a tertiary hospital in Kenya. METHODS: The study was a retrospective survey. All available records of terminally ill patients seen at Aga Khan University Hospital, Nairobi, between July 2010 and December 2015, and that met the inclusion criteria were included in the study. RESULTS: In total, 216 records of terminally ill patients were analyzed: 89 records were of patients that had AD and 127 records were of patients that did not have AD. The proportion of terminally ill patients that had completed AD was 41.2%. The factors that were associated with the completion of AD on bivariate analysis were history of ICU admission, history of endotracheal intubation, functional status of the patient, the medical specialty taking care of the patient, patient's caregiver discussing the AD with the patient, and a palliative specialist review. On multivariate regression analysis, discussion of AD with a caregiver and patient's functional impairment were the factors with statistically significant association with completion of AD. CONCLUSIONS: The proportion of terminally ill patients that had AD in their medical records was significant. However, most terminally ill patients did not have AD. Our data, perhaps the first on the subject in East Africa, suggest that most of the factors associated with AD completion mirrored those seen in other regions of the world. Discussion between patient and their physician and patient's functional impairment were the factors independently associated with completion of AD. Therefore, physicians need to be aware of the importance of discussions of AD with their patients.

Enhancing Postgraduate Medical Education: Upscaling and Recognition of Pakistan's Training.

Null.

The Pulse of AI: Implementation of Artificial Intelligence in Healthcare and its Potential Hazards.

In this editorial, we explore the existing utilization of artificial intelligence (AI) within the healthcare industry, examining both its scope and potential harms if implemented and relied upon on a broader scale. Collaboration among corporations, government bodies, policymakers, and medical experts is essential to address potential concerns, ensuring smooth AI integration into healthcare systems.

Driving pressure in mechanical ventilation: A review.

Driving pressure (∆P) is a core therapeutic component of mechanical ventilation (MV). Varying levels of ∆P have been employed during MV depending on the type of underlying pathology and severity of injury. However, ∆P levels have also been shown to closely impact hard endpoints such as mortality. Considering this, conducting an in-depth review of ∆P as a unique, outcome-impacting therapeutic modality is extremely important. There is a need to understand the subtleties involved in making sure ∆P levels are optimized to enhance outcomes and minimize harm. We performed this narrative review to further explore the various uses of ∆P, the different parameters that can affect its use, and how outcomes vary in different patient populations at different pressure levels. To better utilize ∆P in MV-requiring patients, additional large-scale clinical studies are needed.

Discharging patients home from the intensive care unit: A new trend.

Discharging patients directly to home from the intensive care unit (ICU) is becoming a new trend. This review examines the feasibility, benefits, challenges, and considerations of directly discharging ICU patients. By analyzing available evidence and healthcare professionals' experiences, the review explores the potential impacts on patient outcomes and healthcare systems. The practice of direct discharge from the ICU presents both opportunities and complexities. While it can potentially reduce costs, enhance patient comfort, and mitigate complications linked to extended hospitalization, it necessitates meticulous patient selection and robust post-discharge support mechanisms. Implementing this strategy successfully mandates the availability of home-based care services and a careful assessment of the patient's readiness for the transition. Through critical evaluation of existing literature, this review underscores the significance of tailored patient selection criteria and comprehensive post-discharge support systems to ensure patient safety and optimal recovery. The insights provided contribute evidence-based recommendations for refining the direct discharge approach, fostering improved patient outcomes, heightened satisfaction, and streamlined healthcare processes. Ultimately, the review seeks to balance patient-centered care and effective resource utilization within ICU discharge strategies.

Frameworks for procurement, integration, monitoring, and evaluation of artificial intelligence tools in clinical settings: A systematic review.

Research on the applications of artificial intelligence (AI) tools in medicine has increased exponentially over the last few years but its implementation in clinical practice has not seen a commensurate increase with a lack of consensus on implementing and maintaining such tools. This systematic review aims to summarize frameworks focusing on procuring, implementing, monitoring, and evaluating AI tools in clinical practice. A comprehensive literature search, following PRSIMA guidelines was performed on MEDLINE, Wiley Cochrane, Scopus, and EBSCO databases, to identify and include articles recommending practices, frameworks or guidelines for AI procurement, integration, monitoring, and evaluation. From the included articles, data regarding study aim, use of a framework, rationale of the framework, details regarding AI implementation involving procurement, integration, monitoring, and evaluation were extracted. The extracted details were then mapped on to the Donabedian Plan, Do, Study, Act cycle domains. The search yielded 17,537 unique articles, out of which 47 were evaluated for inclusion based on their full texts and 25 articles were included in the review. Common themes extracted included transparency, feasibility of operation within existing workflows, integrating into existing workflows, validation of the tool using predefined performance indicators and improving the algorithm and/or adjusting the tool to improve performance. Among the four domains (Plan, Do, Study, Act) the most common domain was Plan (84%, n = 21), followed by Study (60%, n = 15), Do (52%, n = 13), & Act (24%, n = 6). Among 172 authors, only 1 (0.6%) was from a low-income country (LIC) and 2 (1.2%) were from lower-middle-income countries (LMICs). Healthcare professionals cite the implementation of AI tools within clinical settings as challenging owing to low levels of evidence focusing on integration in the Do and Act domains. The current healthcare AI landscape calls for increased data sharing and knowledge translation to facilitate common goals and reap maximum clinical benefit.