Feasibility of a hybrid clinical trial for respiratory virus detection in toddlers during the influenza season.

BACKGROUND: Traditional clinical trials are conducted at investigator sites. Participants must visit healthcare facilities several times for the trial procedures. Decentralized clinical trials offer an interesting alternative. They use telemedicine and other technological solutions (apps, monitoring devices or web platforms) to decrease the number of visits to study sites, minimise the impact on daily routine, and decrease geographical barriers for participants. Not much information is available on the use of decentralization in randomized clinical trials with vaccines. METHODS: A hybrid clinical trial may be assisted by parental recording of symptoms using electronic log diaries in combination with home collected nasal swabs. During two influenza seasons, children aged 12 to 35 months with a history of recurrent acute respiratory infections were recruited in 12 primary health centers of the Valencia Region in Spain. Parents completed a symptom diary through an ad hoc mobile app that subsequently assessed whether it was an acute respiratory infection and requested collection of a nasal swab. Feasibility was measured using the percentage of returned electronic diaries and the validity of nasal swabs collected during the influenza season. Respiratory viruses were detected by real-time PCR. RESULTS: Ninety-nine toddlers were enrolled. Parents completed 10,476 electronic diaries out of the 10,804 requested (97%). The mobile app detected 188 potential acute respiratory infections (ARIs) and requested a nasal swab. In 173 (92%) ARI episodes a swab was taken. 165 (95.4%) of these swabs were collected at home and 144 (87.3%) of them were considered valid for laboratory testing. Overall, 152 (81%) of the ARIs detected in the study had its corresponding valid sample collected. CONCLUSIONS: Hybrid procedures used in this clinical trial with the influenza vaccine in toddlers were considered adequate, as we diagnosed most of the ARI cases on time, and had a valid swab in 81% of the cases. Hybrid clinical trials improve participant adherence to the study procedures and could improve recruitment and quality of life of the participants and the research team by decreasing the number of visits to the investigator site. This report emphasises that the conduct of hybrid CTs is a valid alternative to traditional CTs with vaccines. This hybrid CT achieved high adherence of participant to the study procedures. TRIAL REGISTRATION: 2019-001186-33 (EudraCT).

Failure mode and effect analysis for linear accelerator-based paraspinal stereotactic body radiotherapy.

INTRODUCTION: Paraspinal stereotactic body radiotherapy (SBRT) involves risks of severe complications. We evaluated the safety of the paraspinal SBRT program in a large academic hospital by applying failure modes and effects analysis. METHODS: The analysis was conducted by a multidisciplinary committee (two therapists, one dosimetrist, four physicists, and two radiation oncologists). The paraspinal SBRT workflow was segmented into four phases (simulation, treatment planning, delivery, and machine quality assurance (QA)). Each phase was further divided into a sequence of sub-processes. Potential failure modes (PFM) were identified from each subprocess and scored in terms of the frequency of occurrence, severity and detectability, and a risk priority number (RPN). High-risk PFMs were identified based on RPN and were studied for root causes using fault tree analysis. RESULTS: Our paraspinal SBRT process was characterized by eight simulations, 11 treatment planning, nine delivery, and two machine QA sub-processes. There were 18, 29, 19, and eight PFMs identified from simulation, planning, treatment, and machine QA, respectively. The median RPN of the PFMs was 62.9 for simulation, 68.3 for planning, 52.9 for delivery, and 22.0 for machine QA. The three PFMs with the highest RPN were: previous radiotherapy outside the institution is not accurately evaluated (RPN: 293.3), incorrect registration between diagnostic magnetic resonance imaging and simulation computed tomography causing incorrect contours (273.0), and undetected patient movement before ExacTrac baseline (217.8). Remedies to the high RPN failures were implemented, including staff education, standardized magnetic resonance imaging acquisition parameters, and an image fusion process, and additional QA on beam steering. CONCLUSIONS: A paraspinal SBRT workflow in a large clinic was evaluated using a multidisciplinary and systematic risk analysis, which led to feasible solutions to key root causes. Treatment planning was a major source of PFMs that systematically affect the safety and quality of treatments. Accurate evaluation of external treatment records remains a challenge.

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Dermatomicosis

Las dermatomicosis comprenden un amplio espectro de enfermedades que afectan la capa superficial de la piel y la córnea, y atacan principalmente el cabello, la piel y las uñas. Estas enfermedades son consideradas como las micosis más comunes en nuestro medio y a diferencia de la candida y la malassezia que son endógenos, todos los otros hongos tienen hábitat exógeno. El diagnóstico de dichas enfermedades por el laboratorio es relativamente sencillo. El examen directo con KOH es un método sensible, económico y rápido que permite confirmar la presencia del hongo. De otra parte, el cultivo, aunque en algunas enfermedades se puede prescindir de él, es estrictamente necesario para identificar el agente causal, como ocurre en las dermatofitosis y candidiasis. Hasta el momento son estos dos métodos los aceptados y utilizados para el diagnóstico de las dermatomicosis en los laboratorios de refencia de micología, sin embargo, nuevas alternativas diagnósticas, entre ellas la PCR, podrían agilizar el proceso de identificación de los hongos.

[Evolution of stomach cancer mortality in Spain (1951-1985)]. / Evolución de la mortalidad por cáncer de estómago en España (1951-1985).

A descriptive study was made of the trend of the stomach cancer mortality rate in Spain over the period 1951-1985. An upward trend was observed until 1963, and from that time on it gradually decreased in both sexes, though the male population always had a higher rate. By age, the mortality rate showed a clear increase in the fifties, in both sexes. A cohort effect was also clearly evident, the mortality rate was gradually lower in the most recent generations and among the different age groups, which is in keeping with the gradual decrease of the "Potential years in life lost" throughout the time period investigated. The above descriptive data would doubtless be of interest should analytical studies be undertaken.

[Comparative epidemiologic study of mortality caused by leukemia in Spain and the U.S.A. (1951-1983)]. / Estudio epidemiológico comparativo de la mortalidad por leucemias en España y en EE.UU. (1951-1983).

A study of the mortality due to leukaemias in Spain between 1951 and 1983 was performed. A clearly increasing trend was appreciated, with progressive higher affectation of males in the last four years, the mortality rates being constantly higher for this sex. When cytological types of the leukaemias, sex, and the different age groups were taken into account, and after comparing these findings with data reported from the United States of America, it was found that our mortality rates are in general much lower than those of the USA. Although the clinical course of the disease is similar for both countries as regards the four major groups of leukaemias, a striking increase of mortality in childhood (5-9 years) was found here in acute lymphoblastic leukaemia, which suggests, in accordance with our previous reports, high affectation of children in Spain. It seems advisable to improve the techniques and means of treating and preventing complications, especially infectious ones, in childhood.

[Epidemiologic study of mortality caused by cancer of the larynx in Spain, from 1951 to 1983]. / Estudio epidemiológico de la mortalidad por cáncer de laringe en España, período 1951-1983.

We have reviewed the mortality from laryngeal cancer in Spain (1951-1983). An evident increase of the tendency for males has been observed, while an stabilization in females, with lower rates, has been appreciated. It is reflected in the increase of the sex ratio along the studied period, specially since 1970. Concerning the morbidity, through hospital diagnostic data in Spain, as much the absolute numbers as the corresponding morbidity rates have been clearly increasing in males, specially during the last years of our study (1977-1985).

[Investigation of various risk factors associated with colorectal cancer by studying cases and controls]. / Investigación de diversos factores de riesgo asociados al cáncer colorrectal mediante un estudio de casos y controles.

A retrospective study was made of cases of colorectal cancer and controls using 571 cases from various hospitals in Valencia (Spain) and 1,497 controls from the general population with similar sex, age and residence. The relative risks (RR) and levels of statistical significance of various "risk factors" presumably linked to this cancer were calculated. It was associated with: smoking, the Quetelet index (which relates weight and height), chronic constipation and, possibly, sedentary life style, previous cholecystectomy and biliary lithiasis. No association was observed with: civil status, weight, coffee and alcohol intake, or professional status.

[Bladder cancer: study of mortality in Spain (1968-1982)]. / Cáncer de vejiga: Estudio de la mortalidad en España (1968-1982).

In review of the rising bladder cancer mortality rate in Spain and its involvement in connection with other "risk factors", according to recent contributions, we proceeded to review these factors involved and to carry out an epidemiological study describing its mortality from 1968 to 1982, through specific mortality rates per hundred thousand in males and females, as well as the study by age groups from 50 upwards, concentrating on more highly affected ages. We also carried out transverse studies for the three years 1968, 1975 and 1982 and reviewed the evolution of mortality in accordance with the chorts of births. On the whole, we observe a continual rise in mortality due to this cancer, at a much higher level in the masculine sex, and we make interpretation as to its association with "risk factors" connected with life style.