PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study . von Rueden , U. , Gosch , A. , Rajmil , L. , Bisegger , C. , Ravens-Sieberer , U. , the European KIDSCREEN group ( 2006 ) Journal of Epidemiology and Community Health , 60 , 130 – 135 .     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.     

Necrotizing soft tissue infections

Necrotizing soft tissue infections (NSTI) represent a spectrum of diseases characterized by extensive rapidly progressive necrosis that may involve the skin, subcutaneous tissues, fascia or muscle. Their progress is extremely fast, leading often to sepsis and septic shock that ends up in multiple organ failure with abrupt and high mortality. A variety of classification systems have been developed based on parameters such as anatomic location of the disease or microbiology. There are a number of factors that predispose to the spread of these soft tissue infections, such as delays in recognition, immune suppression, diabetes mellitus and advanced age. The use of broad‐spectrum antibiotics tends to mask the severity of the underlying infection, modulates the clinical presentation, and even delays hospital admission. The most important factor affecting outcome in NSTI is early diagnosis and aggressive radical surgical treatment. The medical records of 13 patients who had been treated for NSTI from 1996 to 2005 were reviewed, retrospectively. There were eight men (61.5%) and five (38.5%) women. Mean age was 56 years (range 27–73). Seven cases of infection involved the perineal region (54%), two the lower limb, one the upper limb and three the abdominal wall/trunk. The most common associated comorbidity was diabetes mellitus in five patients (38.5%). A single organism was identified in two (15%) and multiple organisms in 11 (85%) patients. Necrotizing aponeurositis Type I was the most common of the polymicrobial necrotizing infections. Overall survival was 85%, and the mean hospital stay for survivors was 35 days (range 17–92).     

Critical trust: understanding lay perceptions of health and safety risk regulation

The binary opposition of trusting or not trusting is inadequate to understand the often ambiguous and contradictory ideas people possess about risk regulators, particularly when knowledge and experience of such institutions is limited. The paper reports qualitative and quantitative data from a major study of public perceptions (n?=?30 focus groups) of UK risk regulators. We compare the complex and widely different ‘trust profiles’ of two regulatory organisations which are institutionally related (the Health and Safety Executive and the Railways Inspectorate) but very separate in the minds of our participants. The paper develops the notion of critical trust to interrogate the various ways in which people make sense of such organisations, as well as discussing the modes of reasoning that people deploy. The paper argues that views of participants are the outcome of a reconciliation of diverse perceptions concerning the role of the organisation, structural factors and the nature of the regulated risk.     

Skin protection against methylmethacrylate

Ordinary surgical rubber gloves are penetrated by methylmethacrylate monomer (MMA) in less than 1 minute, as demonstrated by gas chromatographic measurements. A three-layered PVP glove, 0.07 mm thick - consisting of an outer layer of polyethylene, an intermediary layer of ethylene vinyl alcohol copolymer, and an inner layer of polyethylene - was impervious for 20 minutes, whereas a viton-butyl rubber glove, 0.27 mm thick, was impervious for 15 minutes.

The PVP glove is recommended to orthopedic surgeons, nurses, and other handling acrylic bone cements to avoid sensitization, and is especially recommended to persons with known contact allergy to MMA.