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The management of sepsis has substantially improved over the past 15 years. In this study, early, goal-directed therapy, which focuses on the initial resuscitation efforts, was compared with usual care for the management of severe sepsis in the United Kingdom. The incidence of severe sepsis and septic shock in adults is estimated to range from 56 to 91 per 100,000 population per year. 1 Affected patients have high rates of death, complications, and resource utilization. 2 – 5 Since 2002, the Surviving Sepsis Campaign (SSC) has promoted best practice, including early recognition, source control, appropriate and timely antibiotic administration, and resuscitation with intravenous fluids and vasoactive drugs. 6 – 8 Resuscitation guidance is largely based on a 2001 single-center, proof-of-concept study by Rivers et al., which indicated that protocolized delivery of 6 hours of early, goal-directed therapy (EGDT) to patients presenting to the emergency department . . .

Published evidence on treatment costs of breast cancer varies widely in methodology and a global systematic review is lacking. This study aimed to conduct a systematic review to compare treatment costs of breast cancer by stage at diagnosis across countries at different levels of socio-economic development, and to identify key methodological differences in costing approaches. MEDLINE, EMBASE, and NHS Economic Evaluation Database (NHS EED) before April 2018. Studies were eligible if they reported treatment costs of breast cancer by stage at diagnosis using patient level data, in any language. Study characteristics and treatment costs by stage were summarised. Study quality was assessed using the Drummond Checklist, and detailed methodological differences were further compared. Twenty studies were included, 15 from high-income countries and five from low- and middle-income countries. Eleven studies used the FIGO staging system, and the mean treatment costs of breast cancer at Stage II, III and IV were 32%, 95%, and 109% higher than Stage I. Five studies categorised stage as in situ, local, regional and distant. The mean treatment costs of regional and distant breast cancer were 41% and 165% higher than local breast cancer. Overall, the quality of studies ranged from 50% (lowest quality) to 84% (highest). Most studies used regression frameworks but the choice of regression model was rarely justified. Few studies described key methodological issues including skewness, zero values, censored data, missing data, and the inclusion of control groups to estimate disease-attributable costs. Treatment costs of breast cancer generally increased with the advancement of the disease stage at diagnosis. Methodological issues should be better handled and properly described in future costing studies.

In this trial, critically ill children were randomly assigned to either tight glycemic control or conventional glycemic control. There was no significant between-group difference in major clinical outcomes, although hypoglycemia was more common with tight glycemic control. Hyperglycemia is a common complication in critical illness and is associated with adverse outcomes. 1 – 5 Single-center, randomized trials have shown that reduction of blood glucose to normal levels with the use of insulin reduces morbidity and mortality among adults in surgical intensive care units (ICUs), 6 with similar effects on morbidity but not on mortality among adults in nonsurgical ICUs. 7 However, two meta-analyses 8 , 9 have failed to show a benefit, and a large, international, multicenter trial showed that tight glycemic control increased mortality. 10 Data on tight glucose control with the use of insulin in critically ill children have been lacking. One . . .

Bullying, aggression, and violence among children and young people are some of the most consequential public mental health problems. We tested the Learning Together intervention, which involved students in efforts to modify their school environment using restorative practice and by developing social and emotional skills. We did a cluster randomised trial, with economic and process evaluations, of the Learning Together intervention compared with standard practice (controls) over 3 years in secondary schools in south-east England. Learning Together consisted of staff training in restorative practice; convening and facilitating a school action group; and a student social and emotional skills curriculum. Primary outcomes were self-reported experience of bullying victimisation (Gatehouse Bullying Scale; GBS) and perpetration of aggression (Edinburgh Study of Youth Transitions and Crime (ESYTC) school misbehaviour subscale) measured at 36 months. We analysed data using intention-to-treat longitudinal mixed-effects models. This trial was registered with the ISRCTN registry (10751359). We included 40 schools (20 in each group); no schools withdrew. 6667 (93·6%) of 7121 students participated at baseline and 5960 (83·3%) of 7154 at 36 months. Mean GBS bullying score at 36 months was 0·34 (SE 0·02) in the control group versus 0·29 (SE 0·02) in the intervention group, with a significant adjusted mean difference (−0·03, 95% CI −0·06 to −0·001; adjusted effect size −0·08). Mean ESYTC score at 36 months was 4·33 (SE 0·20) in the control group versus 4·04 (0·21) in the intervention group, with no evidence of a difference between groups (adjusted difference −0·13, 95% CI −0·43 to 0·18; adjusted effect size −0·03). Costs were an additional £58 per pupil in intervention schools than in control schools. Learning Together had small but significant effects on bullying, which could be important for public health, but no effect on aggression. Interventions to promote student health by modifying the whole-school environment are likely to be one of the most feasible and efficient ways of addressing closely related risk and health outcomes in children and young people. National Institute for Health Research, Educational Endowment Foundation.

Background COVID-19 has caused substantial mortality worldwide, with significant economic consequences. In countries with segmented labour markets, such as Kuwait—where most citizens work in the public sector and most non-Kuwaitis occupy high-exposure essential jobs—the economic impact of premature mortality could be considerably high and these losses may differ across population groups. No prior study in the Gulf region has quantified these losses using established valuation methods. Methods We conducted a retrospective analysis of all confirmed COVID-19 deaths in Kuwait between 2020 and 2022. Years of Potential Life Lost (YPLL) was calculated to measure the epidemiological burden of premature mortality. The economic cost of premature mortality was estimated from a societal perspective using three approaches: the Value of Statistical Life (VSL), the Human Capital Approach (HCA), and the Friction Cost Approach (FCA). Consumption, wage, and employment parameters were drawn from national 2021 surveys, and all estimates were expressed in 2021 international dollars (PPP$). Sensitivity analyses assessed the influence of key assumptions for each method. Results A total of 2,891 COVID-19 deaths occurred during the study period, resulting in approximately 68,000 YPLL, of which 61% were among non-Kuwaitis. Mortality among non-Kuwaiti males was concentrated in working ages, while Kuwaiti deaths occurred primarily in older adults. The total economic burden of premature mortality was estimated at 10.4 billion PPP$ using VSL, 548 million PPP$ using HCA, and 33 million PPP$ using FCA. Kuwaitis accounted for a larger share of VSL and HCA losses, whereas non-Kuwaitis bore the greatest share of YPLL and HCA losses in working ages. Sensitivity analyses showed that VSL results were most affected by discount rate and risk aversion, HCA by age-at-death and wage assumptions, and FCA by vacancy multipliers and friction periods; however, the relative ranking of the methods remained consistent. Conclusions Premature COVID-19 deaths in Kuwait generated a significant economic burden, falling most heavily on non-Kuwaiti working-age men. The findings highlight the need for improved occupational protections, stronger support for migrant workers, and targeted preparedness strategies in countries with similar dual labour-market systems.

The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practiced, but has been associated with harm in paediatric patients. We aimed to evaluate whether conservative oxygenation would reduce duration of organ support or incidence of death compared to standard care. Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in 15 UK paediatric intensive care units (PICUs). Children admitted as an emergency, who were older than 38 weeks corrected gestational age and younger than 16 years receiving invasive ventilation and supplemental oxygen were randomly allocated in a 1:1 ratio via a concealed, central, web-based randomisation system to conservative peripheral oxygen saturations ([SpO2] 88–92%) or liberal (SpO2 >94%) targets. The primary outcome was the duration of organ support at 30 days following random allocation, a rank-based endpoint with death either on or before day 30 as the worst outcome (a score equating to 31 days of organ support), with survivors assigned a score between 1 and 30 depending on the number of calendar days of organ support received. The primary effect estimate was the probabilistic index, a value greater than 0·5 indicating more than 50% probability that conservative oxygenation is superior to liberal oxygenation for a randomly selected patient. All participants in whom consent was available were included in the intention-to-treat analysis. The completed study was registered with the ISRCTN registry (ISRCTN92103439). Between Sept 1, 2020, and May 15, 2022, 2040 children were randomly allocated to conservative or liberal oxygenation groups. Consent was available for 1872 (92%) of 2040 children. The conservative oxygenation group comprised 939 children (528 [57%] of 927 were female and 399 [43%] of 927 were male) and the liberal oxygenation group included 933 children (511 [56%] of 920 were female and 409 [45%] of 920 were male). Duration of organ support or death in the first 30 days was significantly lower in the conservative oxygenation group (probabilistic index 0·53, 95% CI 0·50–0·55; p=0·04 Wilcoxon rank-sum test, adjusted odds ratio 0·84 [95% CI 0·72–0·99]). Prespecified adverse events were reported in 24 (3%) of 939 patients in the conservative oxygenation group and 36 (4%) of 933 patients in the liberal oxygenation group. Among invasively ventilated children who were admitted as an emergency to a PICU receiving supplemental oxygen, a conservative oxygenation target resulted in a small, but significant, greater probability of a better outcome in terms of duration of organ support at 30 days or death when compared with a liberal oxygenation target. Widespread adoption of a conservative oxygenation saturation target (SpO2 88–92%) could help improve outcomes and reduce costs for the sickest children admitted to PICUs. UK National Institute for Health and Care Research Health Technology Assessment Programme.

Unselected multigene testing for all women with breast cancer (BC) identifies more cancer susceptibility gene (CSG) carriers who can benefit from precision prevention compared with family history (FH)/clinical-criteria-based guidelines. Very little CSG testing is undertaken in middle-income countries such as China, and its cost-effectiveness remains unaddressed. We aimed to estimate cost-effectiveness and population impact of multigene testing for all Chinese BC patients. Data from 8085 unselected BC patients recruited to a Peking University Cancer Hospital study were used for microsimulation modeling, comparing three strategies in the Chinese setting: all BC women undergo BRCA1/BRCA2/PALB2 genetic testing, only BC women fulfilling FH/clinical criteria undergo BRCA testing, and no genetic testing. Prophylactic mastectomy and salpingo-oophorectomy would be adopted where appropriate. Societal and payer perspectives with a lifetime horizon along with sensitivity analyses were presented. Incremental cost-effectiveness ratio (ICER): incremental cost per quality-adjusted life-year (QALY) gained is compared to the USD 10,260/QALY (one-times GDP per capita) willingness-to-pay threshold. BC incidence, ovarian cancer (OC) incidence, and related deaths were also estimated. FH/clinical-criteria-based BRCA testing was ruled out on the principle of extensive dominance. Compared with no genetic testing, multigene testing for all BC patients had an ICER = USD 4506/QALY (societal perspective) and USD 7266/QALY (payer perspective), well below our threshold. Probabilistic sensitivity analysis showed unselected multigene testing remained cost-effective for 94.2%/86.6% of simulations from the societal and payer perspectives. One year’s unselected multigene testing could prevent 7868 BC/OC cases and 5164 BC/OC deaths in China. Therefore, unselected multigene testing is extremely cost-effective and should be offered to all Chinese women with BC.

Abstract The Syrian conflict has caused enormous displacement of a population with a high non-communicable disease (NCD) burden into surrounding countries, overwhelming health systems’ NCD care capacity. Médecins sans Frontières (MSF) developed a primary-level NCD programme, serving Syrian refugees and the host population in Irbid, Jordan, to assist the response. Cost data, which are currently lacking, may support programme adaptation and system scale up of such NCD services. This descriptive costing study from the provider perspective explored financial costs of the MSF NCD programme. We estimated annual total, per patient and per consultation costs for 2015–17 using a combined ingredients-based and step-down allocation approach. Data were collected via programme budgets, facility records, direct observation and informal interviews. Scenario analyses explored the impact of varying procurement processes, consultation frequency and task sharing. Total annual programme cost ranged from 4 to 6 million International Dollars (INT$), increasing annually from INT$4 206 481 (2015) to INT$6 739 438 (2017), with costs driven mainly by human resources and drugs. Per patient per year cost increased 23% from INT$1424 (2015) to 1751 (2016), and by 9% to 1904 (2017), while cost per consultation increased from INT$209 to 253 (2015–17). Annual cost increases reflected growing patient load and increasing service complexity throughout 2015–17. A scenario importing all medications cut total costs by 31%, while negotiating importation of high-cost items offered 13% savings. Leveraging pooled procurement for local purchasing could save 20%. Staff costs were more sensitive to reducing clinical review frequency than to task sharing review to nurses. Over 1000 extra patients could be enrolled without additional staffing cost if care delivery was restructured. Total costs significantly exceeded costs reported for NCD care in low-income humanitarian contexts. Efficiencies gained by revising procurement and/or restructuring consultation models could confer cost savings or facilitate cohort expansion. Cost effectiveness studies of adapted models are recommended.

Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper–middle income countries/UMIC) and India (low–middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER =$−5639/QALY; USA-ICER = $ −4018/QALY; Netherlands-ICER =$−11,433/QALY), and it appears cost-effective in UMIC (China-ICER = $ 18,066/QALY; Brazil-ICER =$13,579/QALY), but it is not cost-effective in LMIC (India-ICER = $ 23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER =$21,191/QALY, USA-ICER = $ 16,552/QALY, Netherlands-ICER =$25,215/QALY), and it is cost-effective in UMIC (China-ICER = $ 23,485/QALY, Brazil−ICER =$20,995/QALY), but it is not cost-effective in LMIC (India-ICER = $ 32,217/QALY). BRCA testing costs below$172/test (ICER = $ 19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases.

Background COVID – 19 has had a profound impact on the economy, health systems within countries, and individuals around the world. To provide insight that may enhance the preparedness for future pandemics, a comprehensive cost assessment is vital. This study aims to estimate the direct cost of illness (CoI), as well as the national burden of treating hospitalised COVID-19 patients. Methods This study is prevalence-based retrospective study containing all patients admitted to a single designated hospital in Kuwait for the treatment of COVID-19. Micro (bottom-up) and macro (top-down) costing methods were used to evaluate direct medical CoI from a hospital perspective. Cost components were grouped as consumables, equipment, and human resources, and sensitivity analysis was used to account for uncertainty of inputs. The cost per admission was reported in local currency and international dollars (PPP$). Results Data on 7569 patients was analysed, 52.8% of whom were male, 69.2% were above 41 years, 22% had previously vaccinated for COVID-19, 22% were admitted to the ICU, and 18% had ≥ 3 pre-existing comorbidities. The mean CoI per admission was 12,063 PPP$, with overheads accounting for 45% of this figure, while consumables, human resources, and equipment accounted for 30%, 19%, and 7%, respectively. The sensitivity analysis demonstrated that overall cost uncertainty was primarily driven by variations in human resource costs rather than by uncertainties related to personal protective equipment (PPE) or ventilator use. Conclusion The substantial economic impact of COVID-19 on Kuwait’s healthcare system has emphasised the significant role human resource costs has on overall expenditure. These findings provide valuable insights for future pandemic preparedness.