E-cigarette Use and Severe Coronavirus Disease 2019 (COVID-19) Outcomes: A Meta-Analysis.

E-cigarettes have been known to cause varied poor health outcomes prior to coronavirus disease 2019 (COVID-19), but after the impact of COVID-19, evidence came out that was, in some instances, not as expected regarding the severity of COVID-19 among e-cigarette users (vapers). A meta-analysis was performed on the available evidence to comprehensively find the effect of COVID-19 on existing or past e-cigarette users (vapers). The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were used to perform this meta-analysis. PubMed was searched for observational studies that described outcomes after COVID-19 positivity from December 1, 2019, to December 2023. Medical Subject Headings (MeSH) keywords were used for searching the relevant studies highlighting the relationship between COVID-19 and e-cigarette users. Calculations for pooled prevalence, 95% confidence interval (95% CI), weights for current e-cigarette users and vapers, and outcomes (events) were made. To analyze the data, Review Manager V.5.4 was used. The I² statistic was used to assess statistical heterogeneity. The I² statistic of >50% was considered significant heterogeneity. The "leave-one-out" method was used for sensitivity analysis. Out of 3231 studies, four studies reported data on vaping and non-vaping status and composite outcomes, resulting in a sample size of 653 COVID-19-positive cases. The pooled prevalence of being COVID-19 positive, having symptoms, or visiting an emergency room was 7.78% (653/8392). COVID-19 patients with current vaping status had decreased odds of poor outcomes compared to non-smokers, with a pooled odds ratio (OR) of 0.09 (95% CI 0.00-2.42; p>0.05) with heterogeneity between studies (I²=99%, p=0.15). Because of difficulties related to data collection and other factors, this meta-analysis was unable to conclusively establish the correlation between e-cigarette usage and severe COVID-19 outcomes such as hospitalization, admission to the intensive care unit, and fatality. Additional research using more detailed data is necessary to fully understand this correlation.

Phase I study of temsirolimus in combination with cetuximab in patients with advanced solid tumours.

BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m2, until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways. Paired biopsies were optional to evaluate pathway modulation. RESULTS: Among 39 patients enrolled, three experienced dose-limiting toxicities (DLTs): pulmonary embolism (C200 + T20), stomatitis (C250 + T20) and acneiform rash (C250 + T25). The weekly C 250 mg/m2 and T 25 mg dose level was selected as the MTD. The most common treatment-related adverse events were: acneiform rash (97%), oral mucositis (82%), fatigue (59%), nausea (41%) and diarrhoea (36%). The median progression-free survival (PFS) and overall survival (OS) were respectively 2.0 months [95% CI: 1.8, 3.5] and 7.5 months [95% CI: 5.5, 11.9]. Among all patients, partial responses (PRs) and stable diseases (SDs) were observed in 2 (5.1%) and 18 patients (46.2%), respectively. The objective response rate (ORR) in patients with a molecular aberration was 2/14 (14%), versus 0/24 in those without molecular aberration. CONCLUSIONS: Combination of T + C showed significant but manageable toxicities. Due to modest clinical activity, further evaluation is not recommended. Molecular selection could potentially increase the objective response rate and should be implemented during drug development.

Seeking the driver in tumours with apparent normal molecular profile on comparative genomic hybridization and targeted gene panel sequencing: what is the added value of whole exome sequencing?

BACKGROUND: Molecular tumour profiling technologies have become increasingly important in the era of precision medicine, but their routine use is limited by their accessibility, cost, and tumour material availability. It is therefore crucial to assess their relative added value to optimize the sequence and combination of such technologies. PATIENTS AND METHODS: Within the MOSCATO-01 trial, we investigated the added value of whole exome sequencing (WES) in patients that did not present any molecular abnormality on array comparative genomic hybridization (aCGH) and targeted gene panel sequencing (TGPS) using cancer specific panels. The pathogenicity potential and actionability of mutations detected on WES was assessed. RESULTS: Among 420 patients enrolled between December 2011 and December 2013, 283 (67%) patients were analysed for both TGPS and aCGH. The tumour sample of 25 (8.8%) of them presented a flat (or low-dynamic) aCGH profile and no pathogenic mutation on TGPS. We selected the first eligible 10 samples-corresponding to a heterogeneous cohort of different tumour types-to perform WES. This allowed identifying eight mutations of interest in two patients: FGFR3, PDGFRB, and CREBBP missense single-nucleotide variants (SNVs) in an urothelial carcinoma; FGFR2, FBXW7, TP53, and MLH1 missense SNVs as well as an ATM frameshift mutation in a squamous cell carcinoma of the tongue. The FGFR3 alteration had been previously described as an actionable activating mutation and might have resulted in treatment by an FGFR inhibitor. CREBBP and ATM alterations might also have suggested a therapeutic orientation towards epigenetic modifiers and ataxia-telangectasia and Rad3-related inhibitors, respectively. CONCLUSION: The therapeutic added value of performing WES on tumour samples that do not harbour any genetic abnormality on TGPS and aCGH might be limited and variable according to the histotype. Alternative techniques, including RNASeq and methylome analysis, might be more informative in selected cases.

Antitumor activity in advanced cancer patients with thymic malignancies enrolled in early clinical drug development programs (Phase I trials) at Gustave Roussy.

OBJECTIVES: Thymic epithelial neoplasms (TENs) represent a rare entity with poor prognosis and limited systemic treatment options. The aim of this study was to assess the clinical benefit, the efficacy and toxicities of agents for patients with TEN enrolled in Phase I trials. MATERIALS AND METHODS: We reviewed retrospectively patients with advanced TEN enrolled in Phase I trials at Gustave Roussy (DITEP) between 1994 and 2012. Efficacy was assessed using RECIST version 1.1. RESULTS: Twenty-two treated patients were enrolled (15 with thymic carcinoma, 7 with thymoma). The median number of prior systemic therapies was 2 (0-8). The median age was 50 years (range 23-72), and 4 females were treated. Treatments received encompassed mTOR inhibitor (mTORi) in 4 of patients, antiangiogenic agents (AA) in 11 patients, and other targeted therapies in 7 patients. 18% had grade 3-4 toxicity, 85% all grade toxicity and no toxic death was reported. One patient experienced a complete response (CR) and 3 a partial response (PR); 16 patients had stable disease (median 6.6 months; range 1.0-30.7) and 2 had a progressive disease. The median overall survival was 54.5 months (95% CI 25-75.50). The median progression free survival (PFS) was 6.6 months (95% CI 1.35-11.59). Median PFS was 11.6 months for mTORi, 6.9 for AA, and 6.6 for other targeted therapies. CONCLUSION: Phase I trials appear as a sound therapeutic option in TENs pts progressing after standard treatments. Use of AA and mTORi seem to yield a good clinical response and warrant further investigation.

Who dies from prostate cancer?

BACKGROUND: During the last 30 years, there has been a major shift in initial staging in prostate cancer (CaP) in Western countries, with the incidence of metastases at diagnosis decreasing from over 50% in the 1970s to currently less than 10%. Yet, CaP is still the second cause of cancer death in men. We used two monthly curated databases of patients with castration-resistant prostate cancer (CRPC) to describe the natural history of patients dying of CaP in the modern era. METHODS: The outcome of 190 men with metastatic CRPC treated from 2008 to 2011 was studied. The characteristics of the patients who died from CaP (n = 113 patients, 61%) were analyzed. RESULTS: All 113 patients who died of CaP were assessable for the presence of metastases at diagnosis. Sixty-three patients (56%) had detectable metastases at diagnosis: 67%, 11% and 43% had bone, visceral and lymph node metastases, respectively. The median time to CRPC was 16 months and median overall survival (OS) was 5.2 years.Among the patients with localized CaP at diagnosis (n = 50, 44%), 46% had T stage ⩾ 3 and 38% had a Gleason score ⩾ 8. Overall, 64% of patients were classified as having a high-risk CaP. Only 26% who died from CaP had a Gleason score ⩽ 6. Median OS was 8.8 years. CONCLUSIONS: In the modern era, approximately half of the patients who die from CaP have metastases at diagnosis. The paradigm of progression from localized disease to metastasis and eventually death is only represented in the other half, although possible initial screening and staging errors ought to be taken into consideration. More efforts are needed to conduct trials in patients with newly diagnosed metastatic CaP.

Diferencias relacionadas con la salud de mujeres y hombres adultos mayores / Elderly Men and Women Health Related Differences

La humanidad se enfrenta a la elevación del número de ancianos as. Cuba no es una excepción. La salud en ancianos as es diferente, debido a los factores biológicos, psicológicos y culturales a que están expuestos a lo largo de la vida, de ahí la necesidad de su estudio. Objetivos: identificar las diferencias relacionadas con la salud de mujeres y hombres adultos mayores en el área de salud Cuatro Caminos, durante el año 2009. Métodos: se realizó una investigación descriptiva y transversal. El universo estuvo constituido por los 1 562 ancianos 761 mujeres y 801 hombres residentes en el área de salud Cuatro Caminos. La información se recolectó a través de los registros de adultos mayores, hojas de cargo de los consultorios médicos de la familia, y una entrevista semiestructurada aplicada a la totalidad del universo. Resultados: las edades más representadas para ambos sexos estuvieron entre 60 y 79 años. Tanto mujeres como hombres padecían enfermedades crónicas, destacándose la hipertensión arterial. Las féminas fueron más frecuentes en los ancianos frágiles y en estado de necesidad. Los ancianos solos fueron mayoritariamente hombres. Las mujeres se realizaron más los exámenes periódicos de salud y recibieron atención domiciliaria. Conclusiones. la salud, las actividades que realizan y la atención geriátrica son diferentes en mujeres y hombres adultos mayores...

Mankind faces the increase in the number of elderly. Cuba is no exception. Health in the elderly is different due to the biological, psychological and cultural factors they are exposed through life, hence the need to study. Objective: to identify the differences related to elderly men and women health in Cuatro Caminos area in 2009. Methods: a descriptive cross-sectional study was conducted. The universe consisted of the 1 562 elderly 761 women and 801 men living in the health area of Cuatro Caminos. Information was collected from the records of elderly, daily record of care in family practices, and a semi-structured interview applied to the whole universe.Results: the most represented age for both sexes were between 60 and 79 years. Both women and men suffered from chronic diseases, mainly hypertension. Women were more common in the frail and in need elderly category. Elderly men were mostly living along. In comparison, women had their health periodic reviews more systematically and received home care than men. Conclusions: health, their activities and geriatric care are different in elderly men and women...

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100).

BACKGROUND: Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown. PATIENTS AND METHODS: We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide. Clinical data were retrospectively analysed for prostate-specific antigen (PSA) and RECIST responses, clinical benefit and survival. RESULTS: Thirty-eight patients were included in the analysis. The median age was 71 years (range 52-84); metastatic sites included bone disease in 37 patients (97%), lymph nodes in 15 patients (39%) and visceral disease in 10 patients (26%). Abiraterone was well tolerated. Three patients (8%) attained a PSA response, defined as ≥50% decline in PSA confirmed after ≥4 weeks, while seven patients (18%) had a ≥30% PSA decline. The median progression-free survival (PFS) was 2.7 months (95% CI 2.3-4.1). Of the 12 patients assessable radiologically, only 1 (8%) attained a confirmed partial response. CONCLUSION: Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.

La formación avanzada de investigadores en el ámbito de la atención primaria de salud, una necesidad impostergable / Advanced training of researches in health primary care is an unpostponable need

La investigación constituye un elemento decisivo para el desarrollo de los diferentes contextos sociales, de ahí que se precise su inclusión en los planes de estudios de las universidades médicas cubanas. En el trabajo se realiza un análisis crítico de la situación actual de la enseñanza de la investigación en las universidades médicas, y en la residencia de Medicina General Integral, que sirven de base a la propuesta de estrategia para la formación de investigadores para la Atención Primaria de Salud cubana eslabón fundamental del Sistema Nacional de Salud a través de un proyecto que transitará por varias etapas. Lo integra un grupo multidisciplinario de profesores e investigadores de la Escuela Nacional de Salud Pública y se extenderá desde 2007 hasta 2012.

Research is a decisive element for development of different social contexts, thus, its inclusion is necessary in study plans of Cuban medical universities. In present paper we make a critical analysis of present situation of research teaching in medical universities, and in residency of Integral General Medicine laying the foundations for strategy proposal for the researchers training in Health Primary Care, through a project of some stages. It includes a multidisciplinary group of professors and researchers of National School of Public health extending from 2007 to 2012 years.

Enfoque de género en salud: su importancia y aplicación en la APS / Gender approach in health care: its importance and application in the Primary Health Care

El enfoque de género en salud permite visualizar las iniquidades entre mujeres y hombres, y por tanto realizar intervenciones en correspondencia con las necesidades de cada sexo. Se realizó un análisis documental que permitió explicar la fundamentación teórica y la socialización de género, así como también cómo se manifiesta de acuerdo con las distintas etapas de la vida y las condiciones en que viven los hombres. Se expuso además la utilidad del uso de indicadores que permiten identificar las diferencias entre los sexos, y otros procederes usados para este fin

Tratamiento con mioterapia colectiva a escolares de primaria afectados con labios cortos e incompetentes y/o lengua protractil / Collective exercise therapy for primary school children presenting with short and incompetent lips and/or protactil tongue

Se realizó un estudio a 500 niños de escuela primarias en los municipios Habana Vieja, Playa y 10 de Octubre, en el cual resultaron como normales 100 niños y 400 afectados, los que presentaron unos el labio superior corto e incompetente, otros tenían el hábito deformante de lengua protráctil y un tercer grupo estaba doblemete afectado, pues mostraba el labio superior corto e incompetente y el hábito de lengua protráctil; este grupo se denominó "mixto". El objetivo fundamental del estudio consistió en el tratamiento con la mioterapia colectiva realizado diariamente en las aulas con ejercicios de tipo físicos y mecánicos, los cuales se supervisaron por la auxiliar pedagógica y mensualemtne por el ortodoncista; éstos destacaron resultados positivos al haber recuperado su función el tejido muscular y la deglución su normalidad, e interceptar maloclusiones incipientes; también se comprobó que la mioterapia colectiva es más eficaz que la orientada individualmente

Pirogenicidade de soluçoes de grande volume para uso endovenoso / Pirogenicity of large volume endovenous solutions

Foram estudadas 352 amostras de soluçoes de grande volume compreendendo soluçoes de: glicose a 5%, fisiológica, glicofisiológica, Ringer,Ringer com lactato e manitol. Tais soluçoes foram analisadas quanto à presença de pirogênio nas mesmas. Destas soluçoes, 67 estavam impróprias para utilizaçäo por apresentarem pirogênio com a agravante de que 27 dessas amostras estavam contaminadas com crescimento evidente de fungos e bolores.

Efeitos da esterilizaçäo sobre categutes simples: estudo comparativo entre radiaçäo do Co60 e soluçoes químicas / Effects of sterilization on simple catguts: comparative study between radiation of Co60 and chemical solutions

Foram analisadas 360 amostras de categutes simples esterilizados por radiaçäo gama do Co60, a fim de veificar o efeito da radiaçäo após um período de estocagem superior a dois anos, em termos de degradaçäo protéica. Comparativamente foram estudadas 360 amostras de categutes esterilizados por soluçoes químicas e verificados os seguintes resultados: todas as amostras estavam estéreis, porém, as esterilizadas por radiaçäo liberaram resíduos de degradaçäo protéica

Métodos para controle físico e biológico de categutes simples. Observação sobre o efeito do glioxal / Methods to physical and biological control of simple catgut samples: observation on the effect of glyoxal

Foram desenvolvidos, no Instituto Adolfo Lutz, São Paulo, um processo físico e um processo de digestão enzima tica para verificar se a torção das fitas de colágeno, que constituem o categute, foi perfeita, pois a torção imperfeita diminui a resistência à tração e à digestão. O processo físico substitui com vantagens o método do tensiômetro, pois realiza nós cirúrgicos em placa de borracha mole, de preferência de cor preta, previamente tratada, de consistência semelhante à do tecido muscular estriado. Os categutes, antes de passagem pelo exame físico, também sofreram tratamento (em solução salina a 7%). Este método é usado para verificar a qualidade do categute nas análises de orientação requeri das pelas empresas fabricantes, hospitais e para análises fiscais, que utilizam esse tipo de material cirúrgico. O controle de digestão enzimática de categutes, também desenvolvido no Instituto, tem por objetivo verificar se substâncias estranhas aos conservantes comuns são utilizadas nos categutes, a fim de aumentar sua resistência à tração e à digestibilidade (AU).