Background Septic shock is the most severe form of sepsis, in which profound underlying abnormalities in circulatory and cellular/metabolic parameters lead to substantially increased mortality. A clear understanding and up-to-date assessment of the burden and epidemiology of septic shock are needed to help guide resource allocation and thus ultimately improve patient care. The aim of this systematic review and meta-analysis was therefore to provide a recent evaluation of the frequency of septic shock in intensive care units (ICUs) and associated ICU and hospital mortality. Methods We searched MEDLINE, Embase, and the Cochrane Library from 1 January 2005 to 20 February 2018 for observational studies that reported on the frequency and mortality of septic shock. Four reviewers independently selected studies and extracted data. Disagreements were resolved via consensus. Random effects meta-analyses were performed to estimate pooled frequency of septic shock diagnosed at admission and during the ICU stay and to estimate septic shock mortality in the ICU, hospital, and at 28 or 30 days. Results The literature search identified 6291 records of which 71 articles met the inclusion criteria. The frequency of septic shock was estimated at 10.4% (95% CI 5.9 to 16.1%) in studies reporting values for patients diagnosed at ICU admission and at 8.3% (95% CI 6.1 to 10.7%) in studies reporting values for patients diagnosed at any time during the ICU stay. ICU mortality was 37.3% (95% CI 31.5 to 43.5%), hospital mortality 39.0% (95% CI 34.4 to 43.9%), and 28-/30-day mortality 36.7% (95% CI 32.8 to 40.8%). Significant between-study heterogeneity was observed. Conclusions Our literature review reaffirms the continued common occurrence of septic shock and estimates a high mortality of around 38%. The high level of heterogeneity observed in this review may be driven by variability in defining and applying the diagnostic criteria, as well as differences in treatment and care across settings and countries. Electronic supplementary material The online version of this article (10.1186/s13054-019-2478-6) contains supplementary material, which is available to authorized users.

Purpose To investigate the relationship between chromosomal radiosensitivity and early-onset cancer under age 35 years and to examine the heritability of chromosomal radiosensitivity. Materials and methods Peripheral blood lymphocytes were cultured for 72 hours prior to being irradiated with 0.5 Gy, 300 kV X-rays. Colcemid was added to cultures 30 minutes post-irradiation. Cultures were harvested 90 minutes post-irradiation and analysed for chromatid gaps and breaks. Heritability was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software and by segregation analysis. Results Elevated radiosensitivity was seen for 7 out of 29 (24.1%) cancer survivors, 3 out of 29 (10.3%) partners and 10 out of 53 (20.8%) offspring. Although the proportion of individuals displaying enhanced radiosensitivity was twice as high in both the cancer survivor and offspring groups than the partner controls, neither reached statistical significance. Heritability analysis of the radiosensitive phenotype suggested 57.9 – 78.0% of the variance could be attributed to genetic factors. Conclusions An association between G2 chromosomal radiosensitivity and childhood and young adult cancer is suggested but was not statistically significant. In contrast, there is strong evidence for heritability of the radiosensitive phenotype. The cancer survivors included a broad range of malignancies and future studies should focus on specific cancers with known or likely faults in deoxyribonucleic acid (DNA) damage recognition and repair mechanisms.

A multicolored FISH (mFISH) technique was used to characterize the cytogenetic damage associated with exposure to α-particle radiation with particular emphasis on the quality and quantity that is likely to be transmitted through cell division to descendant cells. Peripheral blood lymphocytes were irradiated in vitro with (238)Pu α particles with a range of mean doses up to 936 mGy and were cultured for 47 h. The dose responses for total aberrant cells, stable and unstable cells, and cells with one simple chromosome aberration and multiple chromosome aberrations were predominantly linear for doses that resulted in cell nuclei receiving a single α-particle traversal. However, there was a decrease per unit dose in aberrant cells of all types at higher doses because of cells increasingly receiving multiple traversals. The proportion of radiation-induced aberrant cells containing multiple aberrations ranged from 48 to 74% with little evidence of dose dependency. Ninety-one percent of all cells with multiple aberrations were classified as unstable. Resolving the chromosome rearrangements into simple categories resulted in a linear dose response for dicentrics of 24.9 ± 3.3 × 10(-2) per Gy. The predominant aberration in stable transmissible cells was a single translocation with a dose response for predominantly single hit cell nuclei of 4.1 ± 1.3 × 10(-2) per Gy. Thus, translocations are the most likely aberration to be observed in peripheral blood lymphocytes from individuals with incorporated α-emitting radionuclides resulting in long-term chronic exposure.

ObjectiveAlthough Markov cohort models represent one of the most common forms of decision-analytic models used in health care decision-making, correct implementation of such models requires reliable estimation of transition probabilities. This study sought to identify consensus statements or guidelines that detail how such transition probability matrices should be estimated.MethodsA literature review was performed to identify relevant publications in the following databases: Medline, Embase, the Cochrane Library, and PubMed. Electronic searches were supplemented by manual-searches of health technology assessment (HTA) websites in Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and the UK. One reviewer assessed studies for eligibility.ResultsOf the 1,931 citations identified in the electronic searches, no studies met the inclusion criteria for full-text review, and no guidelines on transition probabilities in Markov models were identified. Manual-searching of the websites of HTA agencies identified ten guidelines on economic evaluations (Australia, Belgium, Canada, France, Germany, Ireland, Norway, Portugal, Sweden, and UK). All identified guidelines provided general guidance on how to develop economic models, but none provided guidance on the calculation of transition probabilities. One relevant publication was identified following review of the reference lists of HTA agency guidelines: the International Society for Pharmacoeconomics and Outcomes Research taskforce guidance. This provided limited guidance on the use of rates and probabilities.ConclusionsThere is limited formal guidance available on the estimation of transition probabilities for use in decision-analytic models. Given the increasing importance of cost-effectiveness analysis in the decision-making processes of HTA bodies and other medical decision-makers, there is a need for additional guidance to inform a more consistent approach to decision-analytic modeling. Further research should be done to develop more detailed guidelines on the estimation of transition probabilities.

Aim: Management of cutaneous melanoma (CM) is continually evolving with adjuvant treatment of earlier stage disease. The aim of this review was to identify published epidemiological data for stages II–III CM. Materials & methods: Systematic searches of Medline and Embase were conducted to identify literature reporting country/region-specific incidence, prevalence, survival or mortality outcomes in stage II and/or III CM. Screening was carried out by two independent reviewers. Results & conclusion: Of 41 publications, 14 described incidence outcomes (incidence rates per stage were only reported for US and Swedish studies), 33 reported survival or mortality outcomes and none reported prevalence data. This review summarizes relevant data from published literature and highlights an overall paucity of epidemiological data in stages II and III CM.