Development and temporal validation of a prognostic model for 1-year clinical outcome after decompression surgery for lumbar disc herniation.

PURPOSE: Surgeons need tools to provide individualised estimates of surgical outcomes and the uncertainty surrounding these, to convey realistic expectations to the patient. This study developed and validated prognostic models for patients undergoing surgical treatment of lumbar disc herniation, to predict outcomes 1 year after surgery, and implemented these models in an online prediction tool. METHODS: Using the data of 1244 patients from a large spine unit, LASSO and linear regression models were fitted with 90% upper prediction limits, to predict scores on the Core Outcome Measures Index, and back and leg pain. Candidate predictors included sociodemographic factors, baseline symptoms, medical history, and surgeon characteristics. Temporal validation was conducted on 364 more recent patients at the same unit, by examining the proportion of observed outcomes exceeding the threshold of the 90% upper prediction limit (UPL), and by calculating mean bias and other calibration measures. RESULTS: Poorer outcome was predicted by obesity, previous spine surgery, and having basic obligatory (rather than private) insurance. In the validation data, fewer than 12% of outcomes were above the 90% UPL. Calibration plots for the model validation showed values for mean bias < 0.5 score points and regression slopes close to 1. CONCLUSION: While the model accuracy was good overall, the prediction intervals indicated considerable predictive uncertainty on the individual level. Implementation studies will assess the clinical usefulness of the online tool. Updating the models with additional predictors may improve the accuracy and precision of outcome predictions. These slides can be retrieved under Electronic Supplementary Material.

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis.

Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source: Emergency Care Foundation.

Reversibility of nerve root sedimentation sign in lumbar spinal stenosis patients after decompression surgery.

PURPOSE: The nerve root sedimentation sign (SedSign) is a magnetic resonance imaging (MRI) sign for the diagnosis of lumbar spinal stenosis (LSS). It is included in the assessment of LSS to help determine whether decompression surgery is indicated. Assessment of the reversibility of the SedSign after surgery may also have clinical implications for the decision about whether or not a secondary operation or revision is needed. This study investigated if lumbar decompression leads to a reversal of the SedSign in patients with LSS and a positive SedSign pre-operatively; and if a reversal is associated with more favourable clinical outcomes. If reversal of the SedSign is usual after sufficient decompression surgery, a new positive SedSign could be used as an indicator of new stenosis in previously operated patients. METHODS: A prospective cohort study of 30 LSS patients with a positive pre-operative SedSign undergoing decompression surgery with or without instrumented fusion was undertaken to assess the presence of nerve root sedimentation (=negative SedSign) on MRI at 3 months post-operation. Functional limitation (Oswestry Disability Index, ODI), back and leg pain (Visual Analogue Scale, VAS), and treadmill walking distance were also compared pre- and 3 months post-operatively. The short follow-up period was chosen to exclude adjacent segment disease and the potential influence of surgical technique on clinical outcomes at longer follow-up times. RESULTS: 30 patients [median age 73 years (interquartile range (IQR) 65-79), 16 males] showed a median pre-operative ODI of 66 (IQR 52-78), a median VAS of 8 (IQR 7-9), and a median walking distance of 0 m (IQR 0-100). Three months post-operation 27 patients had a negative SedSign. In this group, we found improved clinical outcomes at follow-up: median post-operative ODI of 21 (IQR 12-26), median VAS of 2 (IQR 2-4), and median walking distance of 1000 m (IQR 500-1000). These changes were all statistically significant (p < 0.001). Three patients had a positive SedSign at 3-month follow-up due to epidural fat (n = 2) or a dural cyst following an intra-operative dural tear (n = 1), but also showed improvements in clinical outcomes for ODI, VAS and walking distance. CONCLUSION: The reversibility of a pre-operative positive SedSign was demonstrated after decompression of the affected segmental level and associated with an improved clinical outcome. A persisting positive SedSign could be the result of incomplete decompression or surgical complications. A new positive SedSign after sufficient decompression surgery could be used as an indicator of new stenosis in previously operated patients.

Monitoring of urinary calcium and phosphorus excretion in preterm infants: comparison of 2 methods.

OBJECTIVES: Premature babies require supplementation with calcium (Ca) and phosphorus (P) to prevent metabolic bone disease of prematurity. To guide mineral supplementation, 2 methods of monitoring urinary excretion of Ca and P are used: urinary Ca or P concentration and Ca/creatinine (Crea) or P/Crea ratios. We compare these 2 methods in regards to their agreement on the need for mineral supplementation. METHODS: Retrospective chart review of 230 premature babies with birth weight <1500 g, undergoing screening of urinary spot samples from day 21 of life and fortnightly thereafter. Hypothetical cutoff values for urine Ca or P concentration (1 mmol/L) and urine Ca/Crea ratio (0.5 mol/mol) or P/Crea ratio (4 mol/mol) were applied to the sample results. The agreement on whether to supplement the respective minerals based on the results with the 2 methods was compared. Multivariate general linear models sought to identify patient characteristics to predict discordant results. RESULTS: A total of 24.8% of cases did not agree on the indication for Ca supplementation, and 8.8% for P. Total daily Ca intake was the only patient characteristic associated with discordant results. CONCLUSIONS: With the intention to supplement the respective mineral, comparison of urinary mineral concentration with mineral/Crea ratio is moderate for Ca and good for P. The results do not allow identifying superiority of either method on the decision as to which babies require Ca and/or P supplements.

Increased intraoperative epidural pressure in lumbar spinal stenosis patients with a positive nerve root sedimentation sign.

PURPOSE: The sedimentation sign (SedSign) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). The purpose of this study was to compare the pressure values associated with LSS versus non-LSS and discuss whether a positive SedSign may be related to increased epidural pressure at the level of the stenosis. METHODS: We measured the intraoperative epidural pressure in five patients without LSS and a negative SedSign, and in five patients with LSS and a positive SedSign using a Codman(™) catheter in prone position under radioscopy. RESULTS: Patients with a negative SedSign had a median epidural pressure of 9 mmHg independent of the measurement location. Breath and pulse-synchronous waves accounted for 1-3 mmHg. In patients with monosegmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (median 8-9 mmHg). At the level of the stenosis the median epidural pressure was 22 mmHg. A breath and pulse-synchronous wave was present cranial to the stenosis, but absent below. These findings were independent of the cross-sectional area of the spinal canal at the level of the stenosis. CONCLUSIONS: Patients with LSS have an increased epidural pressure at the level of the stenosis and altered pressure wave characteristics below. We argue that the absence of sedimentation of lumbar nerve roots to the dorsal part of the dural sac in supine position may be due to tethering of affected nerve roots at the level of the stenosis.

Using patient management as a surrogate for patient health outcomes in diagnostic test evaluation.

BACKGROUND: Before a new test is introduced in clinical practice, evidence is needed to demonstrate that its use will lead to improvements in patient health outcomes. Studies reporting test accuracy may not be sufficient, and clinical trials of tests that measure patient health outcomes are rarely feasible. Therefore, the consequences of testing on patient management are often investigated as an intermediate step in the pathway. There is a lack of guidance on the interpretation of this evidence, and patient management studies often neglect a discussion of the limitations of measuring patient management as a surrogate for health outcomes. METHODS: We discuss the rationale for measuring patient management, describe the common study designs and provide guidance about how this evidence should be reported. RESULTS: Interpretation of patient management studies relies on the condition that patient management is a valid surrogate for downstream patient benefits. This condition presupposes two critical assumptions: the test improves diagnostic accuracy; and the measured changes in patient management improve patient health outcomes. The validity of this evidence depends on the certainty around these critical assumptions and the ability of the study design to minimise bias. Three common designs are test RCTs that measure patient management as a primary endpoint, diagnostic before-after studies that compare planned patient management before and after testing, and accuracy studies that are extended to report on the actual treatment or further tests received following a positive and negative test result. CONCLUSIONS: Patient management can be measured as a surrogate outcome for test evaluation if its limitations are recognised. The potential consequences of a positive and negative test result on patient management should be pre-specified and the potential patient benefits of these management changes clearly stated. Randomised comparisons will provide higher quality evidence about differences in patient management using the new test than observational studies. Regardless of the study design used, the critical assumption that patient management is a valid surrogate for downstream patient benefits or harms must be discussed in these studies.

Linking the evidence: intermediate outcomes in medical test assessments.

OBJECTIVES: The aim of this study is to review how health technology assessments (HTA) of medical tests incorporate intermediate outcomes in conclusions about the effectiveness of tests on improving health outcomes. METHODS: Systematic review of English-language test assessments in the HTA database from January 2005 to February 2010, supplemented by a search of the Web sites of International Network of Agencies for Health Technology Assessment (INAHTA) members. RESULTS: A total of 149 HTAs from eight countries were assessed. Half evaluated tests for screening or diagnosis, a third for disease classification (including staging, prognosis, monitoring), and a fifth for multiple purposes. In seventy-one HTAs (48 percent) only diagnostic accuracy was reported, while in seventeen (11 percent) evidence of health outcomes was reported in addition to accuracy. Intermediate outcomes, mainly the impact of test results on patient management, were considered in sixty-one HTAs (41 percent). Of these, forty-seven identified randomized trials or observational studies reporting intermediate outcomes. The validity of these intermediate outcomes as a surrogate for health outcomes was not consistently discussed; nor was the quality appraisal of this evidence. Clear conclusions about whether the test was effective were included in approximately 60 percent of HTAs. CONCLUSIONS: Intermediate outcomes are frequently assessed in medical test HTAs, but interpretation of this evidence is inconsistently reported. We recommend that reviewers explain the rationale for using intermediate outcomes, identify the assumptions required to link intermediate outcomes and patient benefits and harms, and assess the quality of included studies.

Total hip arthroplasty: leg length inequality impairs functional outcomes and patient satisfaction.

BACKGROUND: Leg length inequality (LLI) was identified as a problem of total hip arthroplasty soon after its introduction. Leg lengthening is the most common form of LLI. Possible consequences are limping, neuronal dysfunction and aseptic component loosening. LLI can result in an increased strain both on the contralateral hip joint and on the abductor muscles. We assessed the influence of leg lengthening and shortening on walking capacity, hip pain, limping and patient satisfaction at 2-year follow-up. METHODS: 478 cases with postoperative lengthening and 275 with shortening were identified, and matched with three controls each. Rigorous adjustment for potential differences in baseline patient characteristics was performed by propensity-score matching of covariates. The arbitrarily defined desired outcomes were a walking capacity >60 minutes, no hip pain, no limping, and excellent patient satisfaction. Differences in not achieving the desired outcomes between the groups were expressed as odds ratios. RESULTS: In the lengthened case group, the odds ratio for not being able to walk for an hour was 1.70 (95% CI 1.28-2.26) for cases compared to controls, and the odds ratio for having hip pain at follow-up was 1.13 (95% CI 0.78-1.64). The odds ratio for limping was 2.08 (95% CI 1.55-2.80). The odds ratio for not achieving excellent patient satisfaction was 1.67 (95% CI 1.23-2.28). In the shortening case group, the odds ratio for not being able to walk for an hour was 1.23 (95% CI 0.84-1.81), and the odds ratio for having hip pain at follow-up was 1.60 (95% CI 1.05-2.44). The odds ratio for limping for cases was 2.61 (95% CI 1.78-3.21). The odds ratio for not achieving excellent patient satisfaction was 2.15 (95% CI 1.44-3.21). CONCLUSIONS: Walking capacity, limping and patient satisfaction were all significantly associated with leg lengthening, whereas pain alleviation was not. In contrast, hip pain, limping and patient satisfaction were all significantly associated with leg shortening, whereas walking capacity was not.

Point-of-care prothrombin time testing in paediatric intensive care: an observational study of the ease of use of two devices.

BACKGROUND: Two major difficulties arise when taking blood samples in children: the challenge of venous access and the comparatively large amount of blood required. OBJECTIVE: To assess the value of point-of-care prothrombin time testing in paediatric intensive care patients. We evaluated two point-of-care devices, CoaguChek XS Plus and CoaLine, assessing ease of use in clinical practice and correlation with the standard prothrombin time measurement of the haematology laboratory. DESIGN: Single-centre observational study. SETTING: Between October 2007 and March 2008, patients in an interdisciplinary paediatric ICU of a tertiary centre were analysed. PATIENTS OR OTHER PARTICIPANTS: Thirty-eight patients, 22 female and 16 male (58 and 42%), aged between 0 and 13 years, participated in the study. The intention was to evaluate the ease of use of the devices in daily clinical practice, and no exclusion criteria were applied. MAIN OUTCOME MEASURES: The usefulness of the two point-of-care devices in the paediatric setting was evaluated. Measurements of point-of-care and standard laboratory prothrombin time were compared in terms of agreement and correlation. RESULTS: CoaguChek XS Plus had a failure rate of 2%, CoaLine 17% and the laboratory standard 4%. CoaguChek XS Plus received a better ease of use rating than CoaLine by the study personnel. Compared with the laboratory standard, there was considerable variability of the observed measurements with both devices. The measurements of CoaguChek XS Plus and the standard had a correlation coefficient r of being 0.79. CoaLine and the standard had a correlation coefficient r value of 0.72. CONCLUSION: CoaguChek XS Plus showed 'good' agreement, whereas CoaLine showed 'moderate' agreement compared with prothrombin time values using the standard method. The fast availability of results and the reduction of the required blood volume are advantages of point-of-care tests in the paediatric setting.

Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol.

INTRODUCTION: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity.

INTRODUCTION: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER: CRD42020177408.

High incidence of medication documentation errors in a Swiss university hospital due to the handwritten prescription process.

BACKGROUND: Medication errors have been reported to be a leading cause of death in hospitalized patients. In this study we focused on identifying and quantifying errors in the handwritten drug ordering and dispensing documentation processes which could possibly lead to adverse drug events. METHODS: We studied 1,934 ordered agents (165 consecutive patients) retrospectively for medication documentation errors. Errors were categorized into: Prescribing errors, transcription errors and administration documentation errors on the nurses' medication lists. The legibility of prescriptions was analyzed to explore its possible influence on the error rate in the documentation process. RESULTS: Documentation errors occurred in 65 of 1,934 prescribed agents (3.5%). The incidence of patient charts showing at least one error was 43%. Prescribing errors were found 39 times (37%), transcription errors 56 times (53%), and administration documentation errors 10 times (10%). The handwriting readability was rated as good in 2%, moderate in 42%, bad in 52%, and unreadable in 4%. CONCLUSIONS: This study revealed a high incidence of documentation errors in the traditional handwritten prescription process. Most errors occurred when prescriptions were transcribed into the patients' chart. The readability of the handwritten prescriptions was generally bad. Replacing the traditional handwritten documentation process with information technology could potentially improve the safety in the medication process.

Diagnostic Accuracy of Infection Markers to Diagnose Infections in Neonates and Children Receiving Extracorporeal Membrane Oxygenation.

BACKGROUND: Infections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO. METHODS: Retrospective single center observational study including neonates and children <18 years treated with ECMO in 2015 and 2016. Daily data on PCT, CRP and WCC were assessed in relation to microbiologically confirmed, and clinically suspected infection on ECMO using operating characteristics (ROC) curves. RESULTS: Sixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66-0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61-0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59-0.81) for confirmed and AUC of 0.66 (0.57-0.75) for confirmed and suspected infections. PCT was non-discriminatory. CONCLUSION: The diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO.

Simultaneous bilateral hip replacement reveals superior outcome and fewer complications than two-stage procedures: a prospective study including 1819 patients and 5801 follow-ups from a total joint replacement registry.

BACKGROUND: Total joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period. METHODS: The study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years. RESULTS: Whereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III. CONCLUSIONS: From the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.

Is perioperative point-of-care prothrombin time testing accurate compared to the standard laboratory test?

There is no accepted way of measuring prothrombin time without time loss for patients undergoing major surgery who are at risk of intraoperative dilution and consumption coagulopathy due to bleeding and volume replacement with crystalloids or colloids. Decisions to transfuse fresh frozen plasma and procoagulatory drugs have to rely on clinical judgment in these situations. Point-of-care devices are considerably faster than the standard laboratory methods. In this study we assessed the accuracy of a Point-of-care (PoC) device measuring prothrombin time compared to the standard laboratory method. Patients undergoing major surgery and intensive care unit patients were included. PoC prothrombin time was measured by CoaguChek XS Plus (Roche Diagnostics, Switzerland). PoC and reference tests were performed independently and interpreted under blinded conditions. Using a cut-off prothrombin time of 50%, we calculated diagnostic accuracy measures, plotted a receiver operating characteristic (ROC) curve and tested for equivalence between the two methods. PoC sensitivity and specificity were 95% (95% CI 77%, 100%) and 95% (95% CI 91%, 98%) respectively. The negative likelihood ratio was 0.05 (95% CI 0.01, 0.32). The positive likelihood ratio was 19.57 (95% CI 10.62, 36.06). The area under the ROC curve was 0.988. Equivalence between the two methods was confirmed. CoaguChek XS Plus is a rapid and highly accurate test compared with the reference test. These findings suggest that PoC testing will be useful for monitoring intraoperative prothrombin time when coagulopathy is suspected. It could lead to a more rational use of expensive and limited blood bank resources.

Imaging correlates of the blood-brain barrier disruption in HIV-associated neurocognitive disorder and therapeutic implications.

OBJECTIVE: HIV-associated neurocognitive disorders (HANDs) in the context of suppressive combination antiretroviral therapy (cART) still occur. We explored the role of blood-brain barrier (BBB) disruption in the pathogenesis of HAND in the context of fully suppressive cART using dynamic contrast enhanced perfusion (DCE-P) MRI. DCE-P is a new MRI technique that measures capillary permeability as an indicator for BBB integrity. We hypothesized that virally suppressed incident HAND would be associated with an impaired BBB as determined by DCE-P. DESIGN: A cross sectional study. METHODS: K-trans, a metric derivative of DCE-P, was obtained from different regions of the brain in a cohort of 20 patients with HAND who were virally suppressed in both cerebrospinal fluid (CSF) and blood compared with CSF and blood markers of neuroinflammation as well as with neurometabolites derived from magnetic resonance (MR) spectroscopy. RESULTS: The K-trans data showed significantly impaired BBB in HAND patients when compared with the controls in the regions of the basal ganglia and anterior frontal white matter (both P < 0.0001). CSF neopterin and CSF/serum albumin ratio correlated positively with K-trans but not with blood levels. CONCLUSION: This study indicates that HAND in the context of viral suppression is associated with BBB disruption and the DCE MR derived K-trans metric is a very sensitive parameter to identify the BBB disruption. The finding of region-specific BBB disruption rather than globally and the lack of correlation with blood markers of neuroinflammation suggest that HIV and not systemic inflammation is driving the BBB disturbance and that the BBB disruption is a consequence of HIV already in the brain as opposed to HIV first causing BBB disruption then brain disease.

Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol.

BACKGROUND: There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study. METHODS: This study aims to examine if1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP. This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study. Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data. CONCLUSION: This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.

The Effectiveness and Cost-Effectiveness of Screening for and Vaccination Against Hepatitis B Virus among Migrants in the EU/EEA: A Systematic Review.

Migrants from hepatitis B virus (HBV) endemic countries to the European Union/European Economic Area (EU/EEA) comprise 5.1% of the total EU/EEA population but account for 25% of total chronic Hepatitis B (CHB) infection. Migrants from high HBV prevalence regions are at the highest risk for CHB morbidity. These migrants are at risk of late detection of CHB complications; mortality and onwards transmission. The aim of this systematic review is to evaluate the effectiveness and cost-effectiveness of CHB screening and vaccination programs among migrants to the EU/EEA. We found no RCTs or direct evidence evaluating the effectiveness of CHB screening on morbidity and mortality of migrants. We therefore used a systematic evidence chain approach to identify studies relevant to screening and prevention programs; testing, treatment, and vaccination. We identified four systematic reviews and five additional studies and guidelines that reported on screening and vaccination effectiveness. Studies reported that vaccination programs were highly effective at reducing the prevalence of CHB in children (RR 0.07 95% CI 0.04 to 0.13) following vaccination. Two meta-analyses of therapy for chronic HBV infection found improvement in clinical outcomes and intermediate markers of disease. We identified nine studies examining the cost-effectiveness of screening for CHB: a strategy of screening and treating CHB compared to no screening. The median acceptance of HB screening was 87.4% (range 32.3⁻100%). Multiple studies highlighted barriers to and the absence of effective strategies to ensure linkage of treatment and care for migrants with CHB. In conclusion, screening of high-risk children and adults and vaccination of susceptible children, combined with treatment of CHB infection in migrants, are promising and cost-effective interventions, but linkage to treatment requires more attention.

Interventions to Improve Vaccination Uptake and Cost Effectiveness of Vaccination Strategies in Newly Arrived Migrants in the EU/EEA: A Systematic Review.

Newly arrived migrants to the EU/EEA (arrival within the past five years), as well as other migrant groups in the region, might be under-immunised and lack documentation of previous vaccinations, putting them at increased risk of vaccine-preventable diseases circulating in Europe. We therefore performed a systematic review conforming to PRISMA guidelines (PROSPERO CRD42016045798) to explore: (i) interventions that improve vaccine uptake among migrants; and (ii) cost-effectiveness of vaccination strategies among this population. We searched MEDLINE, Embase, CINAHL, and Cochrane Database of Systematic Reviews (CDSR) between 1 January 2006 to 18 June 2018. We included three primary intervention studies performed in the EU/EEA or high-income countries and one cost effectiveness study relevant to vaccinations in migrants. Intervention studies showed small but promising impact only on vaccine uptake with social mobilization/community outreach, planned vaccination programs and education campaigns. Targeting migrants for catch-up vaccination is cost effective for presumptive vaccination for diphtheria, tetanus, and polio, and there was no evidence of benefit of carrying out pre-vaccination serological testing. The cost-effectiveness is sensitive to the seroprevalence and adherence to vaccinations of the migrant. We conclude that scarce but direct EU/EEA data suggest social mobilization, vaccine programs, and education campaigns are promising strategies for migrants, but more research is needed. Research should also study cost effectiveness of strategies. Vaccination of migrants should continue to be a public heath priority in EU/EEA.