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BACKGROUND: Interest in hereditary lung cancer is increasing, in particular germline mutations in the Epidermal Growth Factor Receptor (EGFR) gene. We review the current literature on this topic, discuss risk of developing lung cancer, treatment and screening options and describe a family of 3 sisters with lung cancer and their unaffected mother all with a rare EGFR germline mutation (EGFR p.R776H). METHODS: We searched PubMed, Medline, Embase, the Cochrane Library, Google Scholar and scanned reference lists of articles. Search terms included "EGFR germline" and "familial lung cancer" or "EGFR familial lung cancer". We also describe our experience of managing a family with rare germline EGFR mutant lung cancer. RESULTS: Although the numbers are small, the described cases in the literature show several similarities. The patients are younger and usually have no or light smoking history. 50% of the patients were treated with a tyrosine kinase inhibitor (TKIs) with OS over six months. CONCLUSION: Although rare, germline p.R776H EGFR lung cancer mutations are over-represented in light or never smoking female patients who often also possess an additional somatic EGFR mutation. Treatment with TKIs appears suitable but further research is needed into the appropriate screening regime for unaffected carriers or light/never smokers.
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Receptores ErbB , Mutação em Linhagem Germinativa , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptores ErbB/genética , Feminino , Pessoa de Meia-Idade , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Predisposição Genética para Doença , Linhagem , Masculino , Idoso , MutaçãoRESUMO
Extracorporeal Cardiopulmonary Resuscitation (ECPR) has potential benefits compared to conventional Cardiopulmonary Resuscitation (CCPR) in children. Although no randomised trials for paediatric ECPR have been conducted, there is extensive literature on survival, neurological outcome and risk factors for survival. Based on current literature and guidelines, we suggest recommendations for deployment of paediatric ECPR emphasising the requirement for protocols, training, and timely intervention to enhance patient outcomes. Factors related to outcomes of paediatric ECPR include initial underlying rhythm, CCPR duration, quality of CCPR, medications during CCPR, cannulation site, acidosis and renal dysfunction. Based on current evidence and experience, we provide an approach to patient selection, ECMO initiation and management in ECPR regarding blood and sweep flow settings, unloading of the left ventricle, diagnostics whilst on ECMO, temperature targets, neuromonitoring as well as suggested weaning and decannulation strategies.
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Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Reanimação Cardiopulmonar/métodos , Criança , Pré-Escolar , Lactente , Masculino , FemininoRESUMO
While healthcare should not be compared to other high reliability organisations (HROs), many lessons, attitudes, and transferable practices can be applied and adapted from them to improve patient safety and team morale. Despite briefings improving both patient safety and effective team working, some in healthcare have not valued or actively engaged with them, deeming them to be irrelevant. In this pilot study we explored the experiences of, and attitudes to, briefings using a 10-question Survey Monkey. This was promoted during a human factors session at the 2023 Association of Surgeons in Training Conference (ASiT) and at a large NHS trust. Questions were asked about the number of briefings per day, attitudes, engagement, and respondents' attitudes to them. In total, 109 responses were received. A total of 85% reported at least one briefing on a normal operating day, 65% felt them to be interactive, 67% reported that briefings were led by the most senior surgical team member, and 58% lasted four minutes or more. Eighteen per cent of respondents felt they were of little benefit, and 56% did not routinely de-brief at the end of the day. This study has highlighted variable attitudes to team briefings, with some colleagues still seeing them as a 'tick box' exercise. While culture has changed following the introduction of the WHO checklist, the importance of active engagement and education to improve the delivery and value of effective briefings cannot be overestimated. It is also an opportunity to create a 'safe space' for team members and to confirm zero tolerance for any inappropriate behaviour, including sexual misconduct.
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Salas Cirúrgicas , Cirurgiões , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Equipe de Assistência ao PacienteRESUMO
Clear communication is paramount for achieving the safest and best patient outcomes, for maximising time efficiency, and lowering clinician workload. Multiple factors contribute to communication efficacy, including knowledge of topics between those communicating, interpersonal familiarity, and available time. Information exchange is growing faster and more frequent due to evolving communication technology, and communication is expanding as a response to increasing workloads. The number of referrals between specialties and the general practitioner (GP) is rising. The use of abbreviations has expanded in clinical communications and is likely to lead to misunderstanding, increased workload, and worse patient outcomes. In this article, we explore the use of abbreviations in the clinical setting.
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Clínicos Gerais , Segurança do Paciente , Humanos , Comunicação , Encaminhamento e Consulta , Carga de TrabalhoRESUMO
AIMS: To evaluate oncological and renal function outcomes of stereotactic body radiotherapy (SBRT) for medically inoperable patients with localised renal cell carcinoma. MATERIALS AND METHODS: Consecutive patients treated with curative intent SBRT (30-45 Gy in five fractions or 42 Gy in three fractions) were included. Data on local control (Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), distant metastasis, impact on estimated glomerular filtration rate (eGFR) and proportional ipsilateral and contralateral renal functions (measured through renal scans) were collected. Univariate and multivariable analyses were conducted to determine association of variables with oncological and renal function outcomes. RESULTS: Seventy-four patients were analysed. The median follow-up was 27.8 months (interquartile range 17.6-41.7). Fifty-seven per cent had tumours ≥ T1b. One-, 2- and 4-year cumulative incidence of local failure was 5.85, 7.77 and 7.77%, respectively. The cumulative incidence of distant metastasis at 2 years was 4.24%. On multivariable analysis, a lower planning target volume (PTV) mean dose (P = 0.019) and a larger PTV (P = 0.005) were significantly associated with the risk of developing local failure. A lower PTV maximum dose (P = 0.039) was significantly associated with the risk of developing distant metastasis. The median change in global eGFR (ml/min) from pre-SBRT levels was -7.0 (interquartile range -14.5 to -1.0) at 1 year and -11.5 (interquartile range -19.5 to -4.0) at 2 years. The proportion of ipsilateral (differential) renal function decreased over time from 47% of overall renal function pre-SBRT to 36% at 2 years, whereas the proportion of contralateral renal function correspondingly improved. On multivariable analysis, a higher volume of uninvolved renal cortex (P < 0.0001) was significantly associated with a smaller decrease in eGFR over time. CONCLUSION: In this large institutional cohort, oncological outcomes of renal cell carcinoma treated with SBRT were favourable and a longitudinal decline in renal function in the ipsilateral kidney and compensatory increase in the contralateral kidney were observed. Clinical and dosimetric factors were significantly associated with oncological and renal function outcomes.
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Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma de Células Renais/radioterapia , Radiocirurgia/efeitos adversos , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Rim/fisiologia , Rim/patologia , Estudos Retrospectivos , Neoplasias Pulmonares/patologiaRESUMO
While healthcare should not be compared to aviation or indeed other high reliability organisations (HROs), many lessons, attitudes, and transferable practices can be applied and, more importantly, adapted from them to improve patient safety and team morale. The team brief before any interventional list is one such process that can have a significant effect on the delivery and safety of patient care and effective team working. Due to NHS pressures and the perception by some in healthcare that the time taken to conduct a full team briefing has little importance, it can sometimes be rushed or regarded as a 'tick box' process that delays a list. However, when used appropriately, the briefing is a chance to lower authority gradients and thereby improve patient safety. It also reduces the likelihood of medical errors, builds and improves situational awareness by considering various 'what-if' scenarios and how they will be dealt with, and considers wider issues including potential distractions. An important outcome is its effect on team morale through empowerment, and it is an opportunity for learning. In this article, which has been written following a unique opportunity to observe a full team brief on an Airbus A380 flight deck, we consider how, through the thorough use of checklists, briefings can be used to best advantage for interventional teams. We raise the question 'would you engage differently with the briefing if your own life or procedure depended on it?'
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Salas Cirúrgicas , Equipe de Assistência ao Paciente , Humanos , Reprodutibilidade dos Testes , Segurança do Paciente , Erros Médicos/prevenção & controleRESUMO
The Critically Endangered southern corroboree frog Pseudophryne corroboree is dependent upon captive assurance colonies for its continued survival. Although the captive breeding programme for this species has largely been successful, embryonic mortality remains high (40-90% per year). This study aimed to investigate the causes of mortality in P. corroboree embryos in the captive collection at Melbourne Zoo. During the 2021 breeding season, we investigated 108 abnormal embryos to determine the impact of infections and anatomical deformities on survival and used culture and molecular methods to identify microbes. Overall, 100% of abnormal embryos had fungal infections, and of these, 41.6% also had anatomical deformities. The mortality rate in abnormal embryos was 89.8%; however, we detected no difference in survival in any of the 3 observed fungal growth patterns or between deformed and non-deformed embryos. Sanger sequencing of the ITS region identified fungal isolates belonging to the genus Ilyonectria, the first record in a vertebrate host, and another as a Plectosphaerella sp., which is the first record of infection in an embryo. Dominant bacteria identified were of the genera Herbaspirillum and Flavobacterium; however, their role in the mortality is unknown. Fungal infection and deformities have a significant impact on embryo survival in captive-bred P. corroboree. In a species which relies on captive breeding, identifying and reducing the impacts of embryonic mortality can inform conservation efforts and improve reintroduction outcomes.
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Anuros , Flavobacterium , Animais , Estações do AnoRESUMO
In the geometric optics approximation, an image formed by an objective lens replicates the distribution of intensity at the front focal plane of the objective. Although this fact represents a fundamental optical principle, its application to analysis of bright-field microscopic images was developed only recently and has not been tested experimentally. In this paper, we applied simple ray tracing to compute an image of a glass cylinder at various positions of the objective and to compare it to the experiment. We obtained a close match between theory and observation, except for a slight underestimation of the intensity in the middle part of the cylinder. The likely reason for this minor difference was constructive interference due to lens-like properties of a cylinder, which could not be accounted for by geometric approximation. We expect that such artefacts would be negligible in imaging of live cells, and the geometric approach would successfully complement the existing quantitative phase methods.
It has become customary to analyse microscopic images in terms of diffraction theory. However, when one is not interested in resolving fine details of an image, a much simpler and more intuitive geometric analysis based on ray tracing can be adequate. We applied geometric approach to analysis of bright-field images of a small glass cylinder at different positions of the objective. Such an object would be very difficult to analyse using diffraction theory because of its high refractive index and steep boundaries. However, ray tracing produced a good match between theory and experiment. It can become a promising approach in bright-field applications, such as quantitative phase imaging.
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The N-acylhydrazone subunit is considered a privileged structure in medicinal chemistry for its importance in pharmaceutical research. Also, alternative methods to deliver these molecules have a great pharmaceutical interest. Therefore, the objective of this work was to encapsulate JR19, an N-acyl hydrazone subunit, into chitosan films and evaluate several properties relevant for transdermal delivery, including biocompatibility using in vitro tests. CHI + JR19 film demonstrates greater strength, flexibility, water absorption capacity, low contact angle and higher surface roughness when compared to CHI. Agar diffusion and 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay show the absence of cytotoxicity and the higher cell viability for CHI + JR19 films. Therefore, the addition of JR19 in the system positively influenced mechanical properties and granted better compatibility with biological environments, showing the potential to treat skin inflammation.
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Quitosana , Preparações Farmacêuticas , Administração Cutânea , Sobrevivência Celular , Química Farmacêutica , Propriedades de SuperfícieRESUMO
Great efforts have been made over the years to assess the effectiveness of air pollution controls in place in the metropolitan area of São Paulo (MASP), Brazil. In this work, the community multiscale air quality (CMAQ) model was used to evaluate the efficacy of emission control strategies in MASP, considering the spatial and temporal variability of fine particle concentration. Seven different emission scenarios were modeled to assess the relationship between the emission of precursors and ambient aerosol concentration, including a baseline emission inventory, and six sensitivity scenarios with emission reductions in relation to the baseline inventory: a 50% reduction in SO2 emissions; no SO2 emissions; a 50% reduction in SO2, NOx, and NH3 emissions; no sulfate (PSO4) particle emissions; no PSO4 and nitrate (PNO3) particle emissions; and no PNO3 emissions. Results show that ambient PM2.5 behavior is not linearly dependent on the emission of precursors. Variation levels in PM2.5 concentrations did not correspond to the reduction ratios applied to precursor emissions, mainly due to the contribution of organic and elemental carbon, and other secondary organic aerosol species. Reductions in SO2 emissions are less likely to be effective at reducing PM2.5 concentrations at the expected rate in many locations of the MASP. The largest reduction in ambient PM2.5 was obtained with the scenario that considered a reduction in 50% of SO2, NOx, and NH3 emissions (1 to 2 µg/m3 on average). It highlights the importance of considering the role of secondary organic aerosols and black carbon in the design of effective policies for ambient PM2.5 concentration control.
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Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Política Ambiental , Aerossóis/análise , Poluição do Ar/análise , Poluição do Ar/legislação & jurisprudência , Poluição do Ar/estatística & dados numéricos , Brasil , Carbono/análise , Monitoramento Ambiental/métodos , Óxidos de Nitrogênio/análise , Material Particulado/análise , Fuligem/análiseRESUMO
Gastric cancers are highly prevalent in both the East and the West, although they differ in aetiology and prognostic outcome. Management of gastric cancer from screening to definitive treatment varies substantially between Eastern and Western countries and regions, owing to numerous factors, including government incentives to carry out population-wide screening programmes to detect early disease, differences in clinical and biological tumour behaviours and responsiveness to treatment, patient accessibility to effective treatment, etc. This review highlights and contrasts the differences in tumour aetiology and histology, as well as the management approaches between the East and the West, which gives important insights and inspirations on future international multicentre research collaboration to combat this dreadful malignancy.
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Neoplasias Gástricas , Humanos , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapiaRESUMO
AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.
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Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Idoso , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The understanding of why air accidents occur and all the factors involved with them has been a strong and constantly evolving driver for improving flight safety. While they are diverse professions, there are many similarities between flying commercial aircraft and surgery, particularly in relation to minimising risk and managing potentially fatal or catastrophic complications. Safety developments in the operating theatre seem to have lagged behind other High Risk Organisations (HROs). A 2018 Quality Care Commission report stated that never events are wholly preventable and expressed the need to learn from other industries. In this article we discuss various transferable lessons and procedures advocated from aviation that could be applied to OMFS in an attempt to improve team culture and safety for our patients.
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Aviação/métodos , Erros Médicos/prevenção & controle , Segurança do Paciente , Cirurgia Bucal/métodos , Humanos , Relações Interprofissionais , Salas Cirúrgicas , Equipe de Assistência ao Paciente/organização & administraçãoRESUMO
Metropolitan areas may suffer with increase of air pollution due to the growth of urbanization, transportation, and industrial sectors. The Metropolitan Area of Vitória (MAV) in Brazil is facing air pollution problems, especially because of the urbanization of past years and of having many industries inside the metropolitan area. Developing air quality system is crucial to understand the air pollution mechanism over these areas. However, having a good input dataset for applying on photochemical models is hard and requires quite of research. One input file for air quality modeling which can play a key role on results is the lateral boundary conditions (LBC). This study aimed to investigate the influence of LBC over CMAQ simulation for particulate matter and ozone over MAV by applying four different methods as LBC during August 2010. The first scenario (M1) is based on a fixed, time-independent boundary conditions with zero concentrations for all pollutants; the second scenario (M2) used a fixed, time-independent concentration values, with average values from local monitoring stations; the third CMAQ nesting scenario (M3) used the nested boundary conditions varying with time from a previous simulation with CMAQ over a larger modeling domain, centered on MAV; and finally, the fourth GEOS-Chem scenario (M4) used the boundary conditions varying with time from simulations of global model GEOS-Chem. All scenarios runs are based on the same meteorology conditions and pollutant emissions. The air quality simulations were made over a domain 61 × 79 km centered on coordinates - 20.25° S, - 40.28° W with a resolution of 1 km. The results were evaluated with the measured data from the local monitoring stations. Overall, significant differences on concentrations and number of chemical species between the LBC scenarios are shown across all LBC scenarios. The M3 and M4 dynamic LBC scenarios showed the best performances over ozone estimates while M1 and M2 had poor performance. Although no LBC scenarios do not seem to have a great influence on total PM10 and PM2.5 concentrations, individual PM2.5 species like Na, NO3-, and NH4+concentrations are influenced by the dynamic LBC approach, since those hourly individual PM2.5 species from CMAQ nesting approach (M3) and GEOS-Chem model (M4) were used as an input to LBC.
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Poluição do Ar/análise , Modelos Teóricos , Ozônio/análise , Poluentes Atmosféricos/análise , Brasil , Cidades , Monitoramento Ambiental/métodos , Desenvolvimento Industrial , Meteorologia/métodos , Material Particulado/análise , Processos FotoquímicosRESUMO
Diuraphis noxia (Kurdjumov), Russian wheat aphid, is one of the world's most invasive and economically important agricultural pests of wheat and barley. In May 2016, it was found for the first time in Australia, with further sampling confirming it was widespread throughout south-eastern regions. Russian wheat aphid is not yet present in New Zealand. The impacts of this pest if it establishes in New Zealand, could result in serious control problems in wheat- and barley-growing regions. To evaluate whether D. noxia could establish populations in New Zealand we used the climate modelling software CLIMEX to locate where potential viable populations might occur. We re-parameterised the existing CLIMEX model by Hughes and Maywald (1990) by improving the model fit using currently known distribution records of D. noxia, and we also considered the role of irrigation into the potential spread of this invasive insect. The updated model now fits the current known distribution better than the previous Hughes and Maywald CLIMEX model, particularly in temperate and Mediterranean areas in Australia and Europe; and in more semi-arid areas in north-western China and Middle Eastern countries. Our model also highlights new climatically suitable areas for the establishment of D. noxia, not previously reported, including parts of France, the UK and New Zealand. Our results suggest that, when suitable host plants are present, Russian wheat aphid could establish in these regions. The new CLIMEX projections in the present study are useful tools to inform risk assessments and target surveillance and monitoring efforts for identifying susceptible areas to invasion by Russian wheat aphid.
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Distribuição Animal , Afídeos , Clima , Modelos Biológicos , Irrigação Agrícola , Animais , Nova ZelândiaRESUMO
There is increasing evidence that treatment beyond second line provides significant survival benefit for selected advanced oesophageal and gastric adenocarcinoma patients, and important randomised controlled trials of both chemotherapy, targeted therapy and immunotherapy have recently been reported in this space. Despite this growing evidence base there are presently no formal guidelines for third line treatment available to clinicians, and as these agents move into routine clinical practice patient selection and rational sequencing of treatment will become an increasingly relevant clinical challenge. This review critically appraises the current evidence base for third line treatment and discusses patient selection, potential predictive biomarkers and future directions for third line treatment in this challenging condition.
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Biomarcadores Tumorais/análise , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Antígeno B7-H1/análise , Antígeno B7-H1/metabolismo , Neoplasias Esofágicas/mortalidade , Humanos , Imunoterapia/métodos , Metanálise como Assunto , Terapia de Alvo Molecular/métodos , Seleção de Pacientes , Neoplasias Gástricas/mortalidadeRESUMO
BACKGROUND: The clinical care of psychiatric patients is often guided by perceptions of suicide risk. The aim of this study was to examine the methods and results of studies reporting high-risk models for inpatient suicide. METHODS: We conducted a registered meta-analysis according to PRISMA guidelines. We searched for relevant peer-reviewed cohort and controlled studies indexed in Medline, EMBASE and PsychINFO. RESULTS: The pooled odds ratio (OR) among 18 studies reporting high-risk models for inpatient suicide was 7.1 [95% confidence interval (CI) 4.2-12.2]. Between-study heterogeneity in ORs was very high (range 0-94.8, first quartile 3.4, median 8.8, third quartile 26.1, prediction interval 0.80-63.1, I2 = 88.1%). The meta-analytically derived sensitivity was 53.1% (95% CI 38.2-67.5%, I2 = 95.9%) and specificity was 84.2% (95% CI 71.6-91.9%, I2 = 99.9%) with an associated meta-analytic area under the curve of 0.83. The positive predictive value of risk categorization among six cohort studies was 0.43% (95% CI 0.014-1.3%, I2 = 95.9%). A history of suicidal behavior and depressive symptoms or affective disorder was included in the majority of high-risk models. CONCLUSIONS: Despite the strength of the pooled association between high-risk categorization and suicide, the very high degree of observed heterogeneity indicates uncertainty about our ability to meaningfully distinguish inpatients according to suicide risk. The limited sensitivity and low positive predictive value of risk categorization suggest that suicide risk models are not a suitable basis for clinical decisions in inpatient settings.