Brief Educational Workshops in Secondary Schools Trial (BESST trial), a school-based cluster randomised controlled trial of the DISCOVER workshop for 16-18-year-olds: recruitment and baseline characteristics.

BACKGROUND: The Brief Educational Workshops in Secondary Schools Trial (BESST) is an England-wide school-based cluster randomised controlled trial assessing the clinical and cost-effectiveness of an open-access psychological workshop programme (DISCOVER) for 16-18-year-olds. This baseline paper describes the self-referral and other recruitment processes used in this study and the baseline characteristics of the enrolled schools and participants. METHOD: We enrolled 900 participants from 57 Secondary schools across England from 4th October 2021 to 10th November 2022. Schools were randomised to receive either the DISCOVER day-long Stress workshop or treatment as usual which included signposting information. Participants will be followed up for 6 months with outcome data collection at baseline, 3-month, and 6-month post randomisation. RESULTS: Schools were recruited from a geographically and ethnically diverse sample across England. To reduce stigma, students were invited to self-refer into the study if they wanted help for stress. Their mean age was 17.2 (SD = 0.6), 641 (71%) were female and 411 (45.6%) were from ethnic minority groups. The general wellbeing of our sample measured using the Mood and Feelings Questionnaire (MFQ) found 314 (35%) of students exhibited symptoms of depression at baseline. Eighty percent of students reported low wellbeing on the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) suggesting that although the overall sample mean is below the cut-off for depression, the self-referral approach used in this study supports distressed students in coming forward. CONCLUSION: The BESST study will continue to follow up participants to collect outcome data and results will be analysed once all the data have been collected. TRIAL REGISTRATION: ISRCTN registry ISRCTN90912799. Registered on 28 May 2020.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Incidence of adverse cardiovascular events in patients with insomnia: A systematic review and meta-analysis of real-world data.

Insomnia is a prevalent sleeping disorder associated with increasing cardiovascular (CV) mortality and morbidity. However, data incorporating recent clinical studies evaluating these outcomes is scarce. Hence, we aimed to investigate the association of insomnia with CV mortality, myocardial infarction (MI), all-cause mortality, and incidence of CV disease by conducting the first-ever meta-analysis of real-world data evaluating these CV outcomes. MEDLINE and Scopus databases were queried till August 2022 to identify studies comparing prespecified outcomes in patients with and without insomnia. The primary outcomes were CV mortality and myocardial infarction, while secondary outcomes included all-cause mortality, and CV-disease incidence. All data were pooled using an inverse-variance weighted random-effects model, and results were reported as relative risks (RRs) and p-values. 21 studies were analyzed. Risks for CV mortality and MI were significantly higher in patients with insomnia (RR 1.53, p<0.01, and RR 1.48, p = 0.03, respectively). The risk for all-cause mortality and CV disease incidence was also significantly higher in insomnia patients (RR 1.14, p = 0.03, and RR 1.31, p<0.01, respectively). Individuals with insomnia experience a higher risk of long-term mortality, MI, and incidence of CV disease.

Crafting a Blueprint for MicroRNA in Cardiovascular Diseases (CVDs).

Cardiovascular diseases (CVDs) encompass a range of disorders, from congenital heart malformation, cardiac valve, peripheral artery, coronary artery, cardiac muscle diseases, and arrhythmias, ultimately leading to heart failure. Despite therapeutic advancements, CVDs remain the primary cause of global mortality, highlighting the need for a thorough knowledge of CVDs at the level of molecular structure. Gene and microRNA (miRNA) expression variations significantly influence cellular pathways, impacting an organism's physiology. MiRNAs, in particular, serve as regulators of gene expression, playing critical roles in essential cellular pathways and influencing the development of various diseases, including CVD. A wealth of evidence supports the involvement of miRNAs in CVD progression. These findings highlight the potential of miRNAs as valuable diagnostic biomarkers and open new avenues for their therapeutic application in CVDs. This study focuses on the latest advancements in identifying and characterizing microRNAs, exploring their manipulation and clinical application, and discussing future perspectives.

Taurine as a potential anti-ageing therapy: the key to reversing the ageing process? Short communication.

Taurine supplementation may be a viable solution to the problem of our cells manufacturing potentially hazardous by-products known as 'free radicals'. Some of these chemicals serve crucial biological activities, but excessive amounts can harm internal cell structures, reducing the cells' capacity to operate. The regulatory systems that contribute to maintaining a healthy balance of reactive oxygen species in the body deteriorate with age. Thus, in this article, we examine how the amino acid taurine could be used in anti-ageing therapy, as well as its mechanism of action, consequences and suggestions.

Comprehensive overview of human monkeypox: epidemiology, clinical features, pathogenesis, diagnosis and prevention.

Monkeypox (MPX) is a zoonotic disease caused by the monkeypox virus (MPXV), belonging to the orthopoxvirus genus with a presentation resembling smallpox making it historically challenging to distinguish the disease from smallpox clinically. Since a British citizen brought MPX into the country on 6 May 2022, there have been concerns about the re-emergence of the human MPXV. Since then, the WHO has reported 92 confirmed cases and 28 suspected cases in 13 nations where MPXV was not endemic. WHO declared MPX a 'public health emergency of international concern' on 23 July 2022. MPXV can spread either through human-human contact or animal-human contact. Respiratory droplets, direct contact with bodily fluids, contaminated patient surroundings or objects, and skin sores from an infected person have all been linked to the disease's transmission from one person to another. Fever, headache, lethargy, asthenia, enlargement of the lymph nodes, weariness, back pain, and myalgia are some of the symptoms that last from 2 to 5 weeks. It can be diagnosed using a range of diagnostic methods, including electron microscopy, Immunoglobulin M, enzyme-linked immunosorbent assay, polymerase chain reactions, histological analysis, immunofluorescent antibody testing, virus isolation, etc. Smallpox immunization before infection may lessen clinical symptoms and is around 85% effective in protecting from the MPXV.

The devastating earthquake that struck Turkey and Syria: Post-traumatic stress disorder and mental health issues among the victims.

Natural catastrophes like earthquakes have the potential to be fatal by claiming lives and harming infrastructure, the environment, and mental health. Victims may experience symptoms such as anxiety, despondency, and post-traumatic stress disorder. Recent earthquakes in Turkey and Syria caused enormous destruction and a high number of fatalities, which is growing by the day. The past examples of earthquakes in China, South Asia, and Turkey imply that there is a possibility that the victims may feel isolated and under psychological stress. Our article outlines the high strategies to minimise the risk of mental health problems among victims of Turkey and Syria.

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.

Urban flooding and risk of leptospirosis; Pakistan on the verge of a new disaster: A call for action.

Leptospirosis is an overlooked zoonotic and waterborne disease that is emerging as a global public threat due to morbidity and mortality observed in both animals and humans. The outbreaks are typically related to floods and hurricanes following monsoon rains, during which Leptospiras are washed off in contaminated soil and often settle in water bodies. Wildlife trapping for scientific purposes, industrial animal employment, water-intensive crop farming, sewage work, and open-water swimming are one of the major risk factors contributing to the rapid spread of disease. Occasionally, outbreaks are linked to higher-than-average precipitation and exposure to contaminated floodwaters that may have contributed to a sudden spike in leptospirosis cases in New Caledonia, Fiji, Vanuatu, and Tanzania. This amplifies the risk of leptospirosis in Pakistan and other nations with urban floods. Therefore, it is of paramount importance to address this health emergency considering the recent surge in leptospirosis cases.

Impact of prolonged flooding in Pakistan: In the middle of unexpected health emergency.

Floods are the most frequent disaster risk factor, and they have significantly increased morbidity and mortality globally. However, the health effects of a specific flood depend on the surrounding circumstances and the current situation in Pakistan indicates that it is leading to a serious health crisis. The immediate health effects of flooding include waterborne and vector-transmitted diseases. The evacuation of patients, loss of medical personnel, and destruction of critical medical supplies and equipment are also overburdening the Pakistani healthcare system. The indirect effects of flooding include infected wounds, poisoning, poor mental health, infectious infections, and famine. Long-term consequences could include starvation, chronic illness, disability, poor mental health, and diseases linked to poverty. In this letter to the editor, we discussed the challenges, efforts, and recommendations that can facilitate the system.

Types of T-cell lymphoma-a cytogenetic perspective.

T cell lymphoma, a type of non-Hodgkin lymphomas is a rare form of malignancy with poor outcomes. TCLS are a heterogeneous group of lymphoid malignancies that occur in nodal and extranodal sites. There are two main types of TCLs namely T-lymphoblastic lymphoma/leukemia and Peripheral T-cell lymphomas classified based on clinical manifestations and cytogenetic mutations. The use of advance technology like karyotyping, fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH) has allowed us to study TCLs in detail and to observe a different biochemical change that occurs in different TCLs allowing us to classify and treat them differently. This review focuses on the different mutations occurring in different TCLs and how they help us distinguish one type from another.

The impact of substance use on health care utilization, treatment, and outcomes in patients with non-small cell lung cancer.

Background: Mortality from non-small cell lung cancer (NSCLC) has improved with screening and novel treatments. The substance use epidemic has threatened health outcomes in a variety of diseases, but little is known about how it is associated with NSCLC outcomes. Methods: We performed a retrospective cohort study of 211 patients with NSCLC treated at a safety-net hospital. Sociodemographic data and clinical outcomes were extracted via review of electronic medical records. Patients were stratified based on substance use status. Comparative and multivariable analyses were performed to evaluate baseline characteristics and lung cancer outcomes including survival. Results: Among 193 patients (91.5%) with information available on substance use, 24.9% reported substance use; specifically, alcohol, marijuana, and illicit substances. Patients with substance use were more likely to have increased health care utilization and poor social determinants of health, including safe housing, stable employment, and social support. There were no significant differences in treatment adherence. Only 6.3% of patients with substance use did not receive guideline concordant care (GCC) compared to 24.8% of patients without substance use; due to poor performance status, increased comorbidities, or loss to follow up. On univariable analysis, patients with substance use experienced inferior median overall survival (OS) if they had metastatic disease (0.40 vs. 1.03 years, P=0.01). However, in the multivariable analysis, substance use did not predict for survival. Independent predictors of mortality were sex (male HR, 1.67; 95% CI: 1.04-2.68; P=0.04), smoking status (current smoking HR, 2.63; 95% CI: 1.14-6.08; P=0.02), and stage (stage IV HR, 14.96; 95% CI: 6.28-35.63; P=0.008). Conclusions: Substance use is associated with poor social determinants of health and increased health care utilization. On multivariable analysis, substance use was not independently associated with OS once guideline-concordant care was used. Future studies should focus on improving our understanding of these associations, delineating potential mechanisms, and developing evidence-based strategies to reduce health care utilization and overcome challenges related to poor social determinants of health.

Olumniant (Baricitinib) oral tablets: An insight into FDA-approved systemic treatment for Alopecia Areata.

Olumniant (Barcitinib) has gained swift approval by the Food and Drug Administration (FDA) as a promising medication for the treatment of adults with severe Alopecia Areata. This drug has proven to be effective for various conditions including Covid-19 and Rheumatoid Arthritis as well as being found to be less costly and minimally invasive, with no need for post-operative management. However, its use has some considerable potential implications before its prescription can be made commonplace. Therefore, more trials need to be conducted to establish a more rigid safety profile.

FDA approves Ruxolitinib (Opzelura) for Vitiligo Therapy: A breakthrough in the field of dermatology.

The Food and Drug Administration (FDA) has authorized Ruxolitinib (Opzelura), as first at-home treatment for non-segmental vitiligo, an autoimmune condition that causes spots and patches of paler skin. Previously, it was used to treat atopic dermatitis, myelofibrosis, essential thrombocythemia, and polycythemia vera. It functions by lowering an individual's enhanced immune response, gradually promoting the development of new, healthy skin cells, and ultimately reintroducing pigment to the afflicted area. Using this topical lotion twice daily can not only produce even skin tones but also boost patients' self-esteem because vitiligo can be physically and psychologically upsetting. It is comparatively more efficacious and has a better safety profile than the oral forms of this medicine, although adverse effects such acne, redness, and itching at the application site, inflammation of the throat and nasal passages, headaches and fever have been observed, necessitating the need for observational studies and randomized controlled trials to demonstrate its efficacy and safety.

Prognostic value of the veterans affairs frailty index in older patients with non-small cell lung cancer.

BACKGROUND: Older patients with non-small cell lung cancer (NSCLC) are a heterogeneous population with varying degrees of frailty. An electronic frailty index such as the Veterans Affairs Frailty Index (VA-FI) can potentially help identify vulnerable patients at high risk of poor outcomes. METHODS: NSCLC patients ≥65 years old and diagnosed in 2002-2017 were identified using the VA Central Cancer Registry. The VA-FI was calculated using administrative codes from VA electronic health records data linked with Medicare and Medicaid data. We assessed associations between the VA-FI and times to mortality, hospitalization, and emergency room (ER) visit following diagnosis by Kaplan-Meier analysis and multivariable stratified Cox models. We also evaluated the change in discrimination and calibration of reference prognostic models after adding VA-FI. RESULTS: We identified a cohort of 42,204 older NSCLC VA patients, in which 55.5% were classified as frail (VA-FI >0.2). After adjustment, there was a strong association between VA-FI and the risk of mortality (HR = 1.23 for an increase of four deficits or, equivalently, an increase of 0.129 on VA-FI, p < 0.001), hospitalization (HR = 1.16 for four deficits, p < 0.001), and ER visit (HR = 1.18 for four deficits, p < 0.001). Adding VA-FI to baseline prognostic models led to statistically significant improvements in time-dependent area under curves and did not have a strong impact on calibration. CONCLUSION: Older NSCLC patients with higher VA-FI have significantly elevated risks of mortality, hospitalizations, and ER visits following diagnosis. An electronic frailty index can serve as an accessible tool to identify patients with vulnerabilities to inform clinical care and research.

Treatment of Rectal Cancer in Older Adults.

PURPOSE OF REVIEW: Rectal cancer is predominantly a disease of older adults but current guidelines do not incorporate the associated specific challenges leading to wide variation in the delivery of cancer care to this subset of population. Here, we will review the current data available regarding the management of rectal cancer in older adults. RECENT FINDINGS: The greatest challenge arises in the management of stage II/III disease as it involves tri-modality treatment that can be harder to tolerate by frail older patients. Response to neoadjuvant treatment is being used as a new marker to tailor further therapy and possibly avoid surgery. Oxaliplatin can be omitted from the adjuvant treatment without compromising outcomes. Physicians should perform geriatric assessment utilizing many validated tools available to help predict treatment tolerability and outcomes in older adults that can help personalize subsequent management. Most older adults can undergo standard therapy for stages I, II, or III rectal cancer with curative intent. Increasing evidence suggests that patients with a clinical complete response to neoadjuvant treatment may be observed closely with the possibility of avoiding surgery. Studies are evaluating alternate systemic treatments for advanced metastatic disease with the hope of maintaining quality of life without compromising cancer outcomes.

CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target.

CK2 genes are overexpressed in many human cancers, and most often overexpression is associated with worse prognosis. Site-specific expression in mice leads to cancer development (e.g., breast, lymphoma) indicating the oncogenic nature of CK2. CK2 is involved in many key aspects of cancer including inhibition of apoptosis, modulation of signaling pathways, DNA damage response, and cell cycle regulation. A number of CK2 inhibitors are now available and have been shown to have activity against various cancers in vitro and in pre-clinical models. Some of these inhibitors are now undergoing exploration in clinical trials as well. In this review, we will examine some of the major cancers in which CK2 inhibition has promise based on in vitro and pre-clinical studies, the proposed cellular and signaling mechanisms of anti-cancer activity by CK2 inhibitors, and the current or recent clinical trials using CK2 inhibitors.