Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries : a prospective, international, multicentre cohort study

Background Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p<0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p<0·001). Interpretation Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Essay 1 : integrating multiple sources of evidence : a Bayesian perspective

Policies and interventions in the health-care system may have a wide range of effects on multiple patient outcomes and operate through many clinical processes. This presents a challenge for their evaluation, especially when the effect on any one patient is small. In this essay, we explore the nature of the health-care system and discuss how the empirical evidence produced within it relates to the underlying processes governing patient outcomes. We argue for an evidence synthesis framework that first models the underlying phenomena common across different health-care settings and then makes inferences regarding these phenomena from data. Bayesian methods are recommended. We provide the examples of electronic prescribing and increased consultant provision at the weekend

Qualitative methods: An alternative view

Are qualitative and quantitative research really based on different philosophies? John Paley and Richard Lilford argue that the idea that qualitative research is constructivist should not be allowed to diffuse into medical literature unopposed

Headroom approach to device development: Current and future directions

OBJECTIVES: The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach. METHODS: Health economic modelling in the supply-side development cycle for new products. RESULTS: The headroom can be used: initially as a 'reality check' on the viability of the device in the healthcare market; to support product development decisions using a real options approach; and to contribute to a pricing policy which respects uncertainties in the reimbursement outlook. CONCLUSIONS: The headroom provides a unifying thread for business decisions along the development cycle for a new product. Over the course of the cycle attitudes to uncertainty will evolve, based on the timing and manner in which new information accrues. Within this framework the developmental value of new information can justify the costs of clinical trials and other evidence-gathering activities. Headroom can function as a simple shared tool to parties in commercial negotiations around individual products or groups of products. The development of similar approaches in other contexts holds promise for more rational planning of service provision

Estimating changes in overall survival using progression-free survival in metastatic breast and colorectal cancer

Objectives: In clinical trials of new cancer drugs, reliable data for progression-free survival will often become available far sooner than reliable data for overall survival. The aim of this study was to determine how many months it would be expected that any given new drug for metastatic breast or colorectal cancer will add to overall survival times given that the number of months the drug adds to progression-free survival times relative to a standard drug is roughly already known.Methods: A literature search was conducted over Medline for randomized controlled trials (RCTs) published between January 1980 and August 2008 that assessed the effect of a drug treatment in comparison to an alternative drug treatment on patients with either metastatic breast or metastatic colorectal cancer.Results: The literature search found 95 and 74 RCTs for metastatic breast and colorectal cancer, respectively, that satisfied the study's inclusion criteria. The results from these trials are consistent, in the case of each of these two metastatic cancers, with gains in time to disease progression being generally associated with no gains or with very slight gains or losses in post-progression survival (i.e., the time between disease progression and death).Conclusions: It would appear that drugs for metastatic breast or colorectal cancer that extend, by a given amount, the time period between the start of treatment and disease progression (i.e., time to progression) have a strong tendency to extend, by roughly the same amount, the period between the start of treatment and death (i.e., overall survival).</jats:p

Stepped-wedge cluster randomised controlled trials : a generic framework including parallel and multiple-level designs

Stepped-wedge cluster randomised trials (SW-CRTs) are being used with increasing frequency in health service evaluation. Conventionally, these studies are cross-sectional in design with equally spaced steps, with an equal number of clusters randomised at each step and data collected at each and every step. Here we introduce several variations on this design and consider implications for power. One modification we consider is the incomplete cross-sectional SW-CRT, where the number of clusters varies at each step or where at some steps, for example, implementation or transition periods, data are not collected. We show that the parallel CRT with staggered but balanced randomisation can be considered a special case of the incomplete SW-CRT. As too can the parallel CRT with baseline measures. And we extend these designs to allow for multiple layers of clustering, for example, wards within a hospital. Building on results for complete designs, power and detectable difference are derived using a Wald test and obtaining the variance–covariance matrix of the treatment effect assuming a generalised linear mixed model. These variations are illustrated by several real examples. We recommend that whilst the impact of transition periods on power is likely to be small, where they are a feature of the design they should be incorporated. We also show examples in which the power of a SW-CRT increases as the intra-cluster correlation (ICC) increases and demonstrate that the impact of the ICC is likely to be smaller in a SW-CRT compared with a parallel CRT, especially where there are multiple levels of clustering. Finally, through this unified framework, the efficiency of the SW-CRT and the parallel CRT can be compared

Comparison of direct and indirect methods of estimating health state utilities for resource allocation: review and empirical analysis

Background and objective Utilities (values representing preferences) for healthcare priority setting are typically obtained indirectly by asking patients to fill in a quality of life questionnaire and then converting the results to a utility using population values. We compared such utilities with those obtained directly from patients or the public

Assessment of publication bias and outcome reporting bias in systematic reviews of health services and delivery research:A meta-epidemiological study

Strategies to identify and mitigate publication bias and outcome reporting bias are frequently adopted in systematic reviews of clinical interventions but it is not clear how often these are applied in systematic reviews relating to quantitative health services and delivery research (HSDR). We examined whether these biases are mentioned and/or otherwise assessed in HSDR systematic reviews, and evaluated associating factors to inform future practice. We randomly selected 200 quantitative HSDR systematic reviews published in the English language from 2007-2017 from the Health Systems Evidence database (www.healthsystemsevidence.org). We extracted data on factors that may influence whether or not authors mention and/or assess publication bias or outcome reporting bias. We found that 43% (n = 85) of the reviews mentioned publication bias and 10% (n = 19) formally assessed it. Outcome reporting bias was mentioned and assessed in 17% (n = 34) of all the systematic reviews. Insufficient number of studies, heterogeneity and lack of pre-registered protocols were the most commonly reported impediments to assessing the biases. In multivariable logistic regression models, both mentioning and formal assessment of publication bias were associated with: inclusion of a meta-analysis; being a review of intervention rather than association studies; higher journal impact factor, and; reporting the use of systematic review guidelines. Assessment of outcome reporting bias was associated with: being an intervention review; authors reporting the use of Grading of Recommendations, Assessment, Development and Evaluations (GRADE), and; inclusion of only controlled trials. Publication bias and outcome reporting bias are infrequently assessed in HSDR systematic reviews. This may reflect the inherent heterogeneity of HSDR evidence and different methodological approaches to synthesising the evidence, lack of awareness of such biases, limits of current tools and lack of pre-registered study protocols for assessing such biases. Strategies to help raise awareness of the biases, and methods to minimise their occurrence and mitigate their impacts on HSDR systematic reviews, are needed

Stakeholder views on publication bias in health services research

Objectives: While the presence of publication bias in clinical research is well documented, little is known about its role in the reporting of health services research. This paper explores stakeholder perceptions and experiences with regard to the role of publication and related biases in quantitative research relating to the quality, accessibility and organization of health services. Methods: We present findings from semi-structured interviews with those responsible for the funding, publishing and/or conduct of quantitative health services research, primarily in the UK. Additional data collection includes interviews with health care decision makers as ‘end users’ of health services research, and a focus group with patient and service user representatives. The final sample comprised 24 interviews and eight focus group participants. Results: Many study participants felt unable to say with any degree of certainty whether publication bias represents a significant problem in quantitative health services research. Participants drew broad contrasts between externally funded and peer reviewed research on the one hand, and end user funded quality improvement projects on the other, with the latter perceived as more vulnerable to selective publication and author over-claiming. Multiple study objectives, and a general acceptance of ‘mess and noise’ in the data and its interpretation was seen to reduce the importance attached to replicable estimates of effect sizes in health services research. The relative absence of external scrutiny, either from manufacturers of interventions or health system decision makers, added to this general sense of ‘low stakes’ of health services research. As a result, while many participants advocated study pre-registration and using protocols to pre-identify outcomes, others saw this as an unwarranted imposition. Conclusions: This study finds that incentives towards publication and related bias are likely to be present, but not to the same degree as in clinical research. In health services research, these were seen as being offset by other forms of ‘novelty’ bias in the reporting and publishing of research findings