Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and ...uncertainty about its effectiveness remains.
We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days.
We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval CI, 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%.
In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).
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.
Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear.
We randomly assigned children (≤16 years of age) who were admitted to the ...pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4.0 to 7.0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12.0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services.
A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0.36 days (95% confidence interval CI, -0.42 to 1.14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter 2.0 mmol per liter) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7.3% vs. 1.5%, P<0.001). Overall, the mean 12-month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12-month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: -$13,120 (95% CI, -$24,682 to -$1,559).
This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U.K. National Health Service; CHiP Current Controlled Trials number, ISRCTN61735247.).
Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat ...patients with ARDS during the 2009 influenza A(H1N1) pandemic.
To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO.
A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching).
Survival to hospital discharge analyzed according to the intention-to-treat principle.
Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk RR, 0.45 95% CI, 0.26-0.79; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 95% CI, 0.31-0.81; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 95% CI, 0.31-0.72; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated.
For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.
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.
Malnutrition is a common problem in critically ill patients in UK NHS critical care units. Early nutritional support is therefore recommended to address deficiencies in nutritional state and related ...disorders in metabolism. However, evidence is conflicting regarding the optimum route (parenteral or enteral) of delivery.
To estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year. Secondary objectives were to compare the route of early nutritional support on duration of organ support; infectious and non-infectious complications; critical care unit and acute hospital length of stay; all-cause mortality at critical care unit and acute hospital discharge, at 90 days and 1 year; survival to 90 days and 1 year; nutritional and health-related quality of life, resource use and costs at 90 days and 1 year; and estimated lifetime incremental cost-effectiveness.
A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation.
Adult general critical care units in 33 NHS hospitals in England.
2400 eligible patients.
Five days of early nutritional support delivered via the parenteral (n = 1200) and enteral (n = 1200) route.
All-cause mortality at 30 days after randomisation and incremental net benefit (INB) (at £20,000 per quality-adjusted life-year) at 1 year.
By 30 days, 393 of 1188 (33.1%) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 (34.2%) assigned to the enteral route had died p = 0.57; absolute risk reduction 1.15%, 95% confidence interval (CI) -2.65 to 4.94; relative risk 0.97 (0.86 to 1.08). At 1 year, INB for the parenteral route compared with the enteral route was negative at -£1320 (95% CI -£3709 to £1069). The probability that early nutritional support via the parenteral route is more cost-effective - given the data - is < 20%. The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia (p = 0.006) and of vomiting (p < 0.001) was significantly lower than in the enteral group. There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups.
Blinding of nutritional support was deemed to be impractical and, although the primary outcome was objective, some secondary outcomes, although defined and objectively assessed, may have been more vulnerable to observer bias.
There was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in England. On average, costs were higher for the parenteral route, which, combined with similar survival and quality of life, resulted in negative INBs at 1 year.
Nutritional support is a complex combination of timing, dose, duration, delivery and type, all of which may affect outcomes and costs. Conflicting evidence remains regarding optimum provision to critically ill patients. There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area.
Current Controlled Trials ISRCTN17386141.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 28. See the NIHR Journals Library website for further project information.
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.
In low and middle‐income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China ...launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost‐effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non‐screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one‐way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality‐adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost‐effectiveness ratio (ICER) of $‐916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost‐effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.
What's new?
Whilst breast cancer incidence is lower among women in rural areas, mortality is higher due to lower access to screening, diagnosis, and treatment. China thus launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. This study aimed to analyse the cost‐effectiveness of breast cancer screening compared with no screening. The findings reveal overall reduction in health‐related quality of life due to false‐positives, with breast cancer screening doing more harm than good. Priority should be given to offering symptomatic women proper access to early diagnosis and treatment.
Background
Understanding the health care activity and associated hospital costs of caring for people living with HIV is an important component of assessing the cost effectiveness of new technologies ...and for budget planning.
Methods
Data collected between 2010 and 2017 from an English HIV treatment centre were combined with national reference costs to estimate the rate of hospital attendances and costs per quarter year, according to demographic and clinical factors. The final dataset included records for 1763 people living with HIV, which was analysed using negative binomial regression models and general estimating equations.
Results
People living with HIV experienced an unadjusted average of 0.028 (standard deviation SD 0.20) inpatient episodes per quarter, equivalent to one every 9 years, and 1.85 (SD 2.30) outpatient visits per quarter. The unadjusted mean quarterly cost per person with HIV (excluding antiretroviral drug costs) was £439 (SD 604). Outpatient appointments and inpatient episodes accounted for 88% and 6% of total costs, respectively. In adjusted models, low CD4 count was the strongest predictor of inpatient stays and outpatient visits. Low CD4 count and new patient status (having a first visit at the Trust in the last 6 months) were the factors that most increased estimated costs. Associations were weaker or less consistent for demographic factors (age, sex/sexual orientation/ethnicity). Sensitivity analyses suggest that the findings were generally robust to alternative parameter and modelling assumptions.
Conclusion
A number of factors predicted hospital activity and costs, but CD4 cell count and new patient status were the strongest. The study results can be incorporated into future economic evaluations and budget impact assessments of HIV‐related technologies.
Background In China, breast cancer is the most frequently diagnosed cancer in women. Marked disparities between urban and rural populations have been reported for breast cancer incidence and ...survival. In 2009, China launched a breast cancer screening programme for women living in rural areas who were aged 35–64 years and at average risk. The programme used ultrasound combined with clinical breast examination as the primary screening tool. In 2012, breast cancer screening was done by use of ultrasound, and was followed by mammography among women living in urban areas aged 40–69 years, who were high risk and were identified through risk assessment questionnaires. To date, economic evidence is still scarce. This study aimed to analyse the cost-effectiveness of breast cancer screening compared with no screening among women in rural and urban China. Methods We developed a Markov model to estimate the lifetime costs and effects, from a societal perspective, for the general population-based cohorts, both in urban China with high incidence of breast cancer and rural China with low incidence of breast cancer. Analyses were done for women in rural areas aged 35 years and women in urban areas aged 40 years. Women who were asymptomatic in the intervention arm were screened every 3 years. Breast cancer in the non-screening arm could only be diagnosed on presentation of symptoms. The main outcome measure was cost per quality-adjusted life-year (QALY) gained with a 3% annual discount. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Findings Compared with no screening, the rural breast cancer screening programme cost US$186·72 more and led to a loss of 0·20 QALYs because of disutility from false positives. Breast cancer screening among women in rural China is more expensive, with an incremental cost-effectiveness ratio (ICER) of $-916 per QALY, compared with no screening. In urban areas, the breast cancer screening programme cost $84·99 and gained 0·01 QALYs, with an ICER of $6671 per QALY, well below the willingness-to-pay threshold of $23 050 per QALY at three times GDP per capita (2014) in China. The results are shown to be robust through the sensitivity analyses. Interpretation In a rural setting, which has low breast cancer incidence, screening for asymptomatic disease among the general population using current screening tools is not cost-effective. Priority should be given to ensure that women who are symptomatic have access to diagnosis and treatment at an early stage. In urban China, a high-risk population-based screening method for breast cancer is very likely to be cost-effective compared with no screening. Funding National Natural Science Foundation of China (71273016 and 71673004).
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