The Effectiveness of Interventions for the Prevention or Treatment of Paternal Perinatal Anxiety: A Systematic Review.

Background: The worldwide prevalence of paternal perinatal anxiety (PPA) ranges between 3.4% and 25.0% antenatally, and 2.4% and 51.0% postnatally. Experiencing PPA can adversely impact the individual, partners, and infants. Research concerning PPA is lagging and fragmented compared to research for new mothers. Objectives: To establish the effectiveness of prevention or treatment interventions for PPA in adults identifying as male. Data sources: We completed searches of Medline, EMBASE, PsycINFO and Web of Science from inception to 2 December 2021, as well as hand searches of references from relevant papers. Search selection and data extraction: Randomised controlled trials delivering prevention or treatment interventions and reporting anxiety outcomes for new/expectant fathers in the perinatal mental health period were included. Our review follows the PRISMA reporting guidelines. One reviewer independently screened 5170 titles/abstracts; second reviewers screened 50%. Two reviewers independently screened full text, extracted data, and conducted risk of bias assessments. Synthesis: Cochrane's collaboration tool 2 was used to assess quality. Primarily results are synthesised narratively, a post-hoc sub-group analysis was completed on four studies using the same outcome measure. Main results: Twelve of the 5170 studies fulfilled the inclusion criteria. Studies used psychoeducational or practical skills interventions. Interventions mostly involved couple-dyads and three studies assessed PPA as a primary outcome. Included interventions were prevention-based; no treatment interventions were found. Father-only interventions consistently reported a significant reduction of PPA. Conclusions: Systematic searching yielded no treatment interventions, highlighting a substantial gap in the evidence base. Within a limited and heterogenous sample, no studies targeted diagnosed PPA. Evidence suggested father-focused interventions may be effective in preventing PPA, regardless of the intervention delivery mode or intervention content. However, consistency between study design and options within the field are lacking compared to interventions available for mothers.

Cost-effectiveness of testing for latent tuberculosis infection in people with HIV.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of screening strategies for predicting LTBI that progresses to active tuberculosis (TB) in people with HIV. DESIGN: We developed a decision-analytical model that constituted a decision tree covering diagnosis of LTBI and a Markov model covering progression to active TB. The model represents the lifetime experience following testing for LTBI, and discounting costs, and benefits at 3.5% per annum in line with UK standards. We undertook probabilistic and one-way sensitivity analyses. SETTING: UK National Health Service and Personal Social Service perspective in a primary care setting. PARTICIPANTS: Hypothetical cohort of adults recently diagnosed with HIV. INTERVENTIONS: Interferon-gamma release assays and tuberculin skin test. MAIN OUTCOME MEASURE: Cost per quality-adjusted life year (QALY). RESULTS: All strategies except T-SPOT.TB were cost-effective at identifying LTBI, with the QFT-GIT-negative followed by TST5mm strategy being the most costly and effective. Results indicated that there was little preference between strategies at a willingness-to-pay threshold of £20 000. At thresholds above £40 000 per QALY, there was a clear preference for the QFT-GIT-negative followed by TST5mm, with a probability of 0.41 of being cost-effective. Results showed that specificity for QFT-GIT and TST5mm were the main drivers of the economic model. CONCLUSION: Screening for LTBI has important public health and clinical benefits. Most of the strategies are cost-effective. These results should be interpreted with caution because of the paucity of studies included in the meta-analysis of test accuracy studies. Additional high-quality primary studies are needed to have a definitive answer about, which strategy is the most effective.

Creation and observation of Hopfions in magnetic multilayer systems.

Among topological solitons, magnetic skyrmions are two-dimensional particle-like objects with a continuous winding of the magnetization, and magnetic Hopfions are three-dimensional objects that can be formed from a closed loop of twisted skyrmion strings. Theoretical models suggest that magnetic Hopfions can be stabilized in frustrated or chiral magnetic systems, and target skymions can be transformed into Hopfions by adapting their perpendicular magnetic anisotropy, but their experimental verification has been elusive so far. Here, we present an experimental study of magnetic Hopfions that are created in Ir/Co/Pt multilayers shaped into nanoscale disks, known to host target skyrmions. To characterize three-dimensional spin textures that distinguish Hopfions from target skyrmions magnetic images are recorded with surface-sensitive X-ray photoemission electron microscopy and bulk-sensitive soft X-ray transmission microscopy using element-specific X-ray magnetic circular dichroism effects as magnetic contrast. These results could stimulate further investigations of Hopfions and their potential application in three-dimensional spintronics devices.

Mobile Clinical Decision Support System for the Management of Diabetic Patients With Kidney Complications in UK Primary Care Settings: Mixed Methods Feasibility Study.

BACKGROUND: Attempts to utilize eHealth in diabetes mellitus (DM) management have shown promising outcomes, mostly targeted at patients; however, few solutions have been designed for health care providers. OBJECTIVE: The purpose of this study was to conduct a feasibility project developing and evaluating a mobile clinical decision support system (CDSS) tool exclusively for health care providers to manage chronic kidney disease (CKD) in patients with DM. METHODS: The design process was based on the 3 key stages of the user-centered design framework. First, an exploratory qualitative study collected the experiences and views of DM specialist nurses regarding the use of mobile apps in clinical practice. Second, a CDSS tool was developed for the management of patients with DM and CKD. Finally, a randomized controlled trial examined the acceptability and impact of the tool. RESULTS: We interviewed 15 DM specialist nurses. DM specialist nurses were not currently using eHealth solutions in their clinical practice, while most nurses were not even aware of existing medical apps. However, they appreciated the potential benefits that apps may bring to their clinical practice. Taking into consideration the needs and preferences of end users, a new mobile CDSS app, "Diabetes & CKD," was developed based on guidelines. We recruited 39 junior foundation year 1 doctors (44% male) to evaluate the app. Of them, 44% (17/39) were allocated to the intervention group, and 56% (22/39) were allocated to the control group. There was no significant difference in scores (maximum score=13) assessing the management decisions between the app and paper-based version of the app's algorithm (intervention group: mean 7.24 points, SD 2.46 points; control group: mean 7.39, SD 2.56; t37=-0.19, P=.85). However, 82% (14/17) of the participants were satisfied with using the app. CONCLUSIONS: The findings will guide the design of future CDSS apps for the management of DM, aiming to help health care providers with a personalized approach depending on patients' comorbidities, specifically CKD, in accordance with guidelines.

Colonies of threaded rings in excitable media.

A thring is a recent addition to the zoo of spiral wave phenomena found in excitable media and consists of a scroll ring that is threaded by a pair of counter-rotating scroll waves. This arrangement behaves as a particle that swims through the medium. Here, we present results on the dynamics, interaction, and collective behavior of several thrings via numerical simulation of the reaction-diffusion equations that model thrings created in chemical experiments. We reveal an attraction between two thrings that leads to a stable bound pair that thwarts their individual locomotion. Furthermore, such a pair emits waves at a higher frequency than a single thring, which protects the pair from the advances of any other thring and rules out the formation of a triplet bound state. As a result, the long-term evolution of a colony of thrings ultimately yields an unusual frozen nonequilibrium state consisting of a collection of pairs accompanied by isolated thrings that are inhibited from further motion by the waves emanating from the pairs.

Comparison of health technology assessment for new medicines in France and England: an example based on ixazomib for patients with relapsed or refractory multiple myeloma.

Introduction: The appraisal of medicines is often a complex and iterative process. We compared the health technology assessment (HTA) process in England and France taking as a case study the example of ixazomib for multiple myeloma. Methods: We undertook an analysis of eight relevant published documents identifed from the websites of the French and English HTA bodies (HAS and NICE, respectively). We analyse patients' availability of ixazomib resulting in the different stages of the appraisal process. Results: We identified differences in the assessment, one of these being the use of an appraisal scope in England allowing the differentiation of populations and comparators according to previously approved treatments. Ixazomib became available earlier in France as part of an early access programme, but the availability was soon discontinued for newly eligible patients following an HAS determination that Ixazomib yielded no additional benefit. This opinion resulted in long pricing discussions. In England, despite the absence of an early access programme and following a process that included cost-effectiveness evaluation combined with pricing discussions, the medicine was fairly rapidly recommended for use. Conclusions: Differences in the HTA process may result in appreciable differences in time from marketing authorisation to health service adoption of newly licensed drugs.

Threaded Rings that Swim in Excitable Media.

Cardiac tissue and the Belousov-Zhabotinsky reaction provide two notable examples of excitable media that support scroll waves, in which a filament core is the source of spiral waves of excitation. Here we consider a novel topological configuration in which a closed filament loop, known as a scroll ring, is threaded by a pair of counterrotating filaments that are perpendicular to the plane of the ring and end on the boundary of a thin medium. We simulate the dynamics of this threaded ring (thring) in the photosensitive Belousov-Zhabotinsky excitable medium, using the modified Oregonator reaction-diffusion equations. These computations reveal that the threading topology induces an exotic motion in which the thring swims in the plane of the ring. We propose a light templating protocol to create a thring in the photosensitive Belousov-Zhabotinsky medium and provide experimental confirmation that this protocol indeed yields a thring.

Skyrmions and Clustering in Light Nuclei.

One of the outstanding problems in modern nuclear physics is to determine the properties of nuclei from the fundamental theory of the strong force, quantum chromodynamics (QCD). Skyrmions offer a novel approach to this problem by considering nuclei as solitons of a low energy effective field theory obtained from QCD. Unfortunately, the standard theory of Skyrmions has been plagued by two significant problems: (1) It yields nuclear binding energies that are an order of magnitude larger than experimental nuclear data, and (2) it predicts intrinsic shapes for nuclei that fail to match the clustering structure of light nuclei. Here we show that extending the standard theory of Skyrmions, by including the next lightest subatomic meson particles traditionally neglected, dramatically improves both of these aspects. We find Skyrmion clustering that now agrees with the expected structure of light nuclei, with binding energies that are much closer to nuclear data.

A randomised controlled trial of the impact of structured written and verbal advice by community pharmacists on improving hypertension education and control in patients with high blood pressure.

PURPOSE: This study was aimed to determine whether structured written and verbal education provided to patients by community pharmacists about high blood pressure (BP) and its treatment would be (a) better retained and (b) be associated with improved BP control as compared to patients receiving verbal advice only. METHODS: The study was designed as a randomised controlled trial and was conducted in the West Midlands, UK, between January 2014 and June 2014. The primary outcome measures were differences in systolic and diastolic BP from baseline and retention of information about high BP assessed with a questionnaire at 2-, 4- and 26-week follow-up points. RESULTS: A total of 64 adults were included in the study. At the week 26 follow-up, compared to participants in the control group, there was a significant improvement in the knowledge of intervention participants about the risks associated with high BP (p < 0.001) and awareness about potential adverse effects of the new BP medicine (p < 0.001). Similarly, there was a greater and more significant reduction in systolic BP in favour of the intervention group 8 mmHg (95% CI 2.1-13.3 p = 0.009) compared to 6 mmHg (95% CI 0.6-11.7 p = 0.02) in the control group at the week 4 follow-up. However, this greater effect of an intervention on BP was not sustained at the 26-week follow-up. For diastolic BP, there was no added effect of the intervention. CONCLUSION: This randomised controlled trial suggests that although written advice provided by community pharmacists in comparison to verbal advice was more effective in improving knowledge and understanding of patients about hypertension and its treatment, it did not lead to better blood pressure control.

Effectiveness and impact of networked communication interventions in young people with mental health conditions: A rapid review.

OBJECTIVE: To describe the latest evidence of effectiveness and impact of networked communication interventions for young people with mental health conditions. METHODS: Searching five databases from 2009 onwards, we included studies of any design investigating two-way communication interventions for the treatment of young people (mean age 12-25) with a chronic mental health disorder. The data were synthesised using narrative summary. RESULTS: Six studies met the inclusion criteria, covering a range of mental health conditions (depression, psychosis, OCD). Interventions included an online chat room (n = 2), videoconferencing (n = 3) and telephone (n = 1). Where studies compared two groups, equivalence or a statistically significant improvement in symptoms was observed compared to control. Views of patients and clinicians included impact on the patient-clinician interaction. Clinicians did not feel it hindered their diagnostic ability. CONCLUSION: Networked communication technologies show promise in the treatment of young people with mental health problems but the current available evidence remains limited and the evidence base has not advanced much since the previous inception of this review in 2011. PRACTICE IMPLICATIONS: Although the available research is generally positive, robust evidence relating to the provision of care for young persons via these technologies is lacking and healthcare providers should be mindful of this.

Digital Clinical Communication for Families and Caregivers of Children or Young People With Short- or Long-Term Conditions: Rapid Review.

BACKGROUND: The communication relationship between parents of children or young people with health conditions and health professionals is an important part of treatment, but it is unclear how far the use of digital clinical communication tools may affect this relationship. OBJECTIVE: The objective of our study was to describe, assess the feasibility of, and explore the impact of digital clinical communication between families or caregivers and health professionals. METHODS: We searched the literature using 5 electronic databases. We considered all types of study design published in the English language from January 2009 to August 2015. The population of interest included families and caregivers of children and young people aged less than 26 years with any type of health condition. The intervention was any technology permitting 2-way communication. RESULTS: We included 31 articles. The main designs were randomized controlled trials (RCTs; n=10), cross-sectional studies (n=9), pre- and postintervention uncontrolled (pre/post) studies (n=7), and qualitative interview studies (n=2); 6 had mixed-methods designs. In the majority of cases, we considered the quality rating to be fair. Many different types of health condition were represented. A breadth of digital communication tools were included: videoconferencing or videoconsultation (n=14), and Web messaging or emails (n=12). Health care professionals were mainly therapists or cognitive behavioral therapists (n=10), physicians (n=8), and nurses (n=6). Studies were very heterogeneous in terms of outcomes. Interventions were mainly evaluated using satisfaction or acceptance, or outcomes relating to feasibility. Clinical outcomes were rarely used. The RCTs showed that digital clinical communication had no impact in comparison with standard care. Uncontrolled pre/post studies showed good rates of satisfaction or acceptance. Some economic studies suggested that digital clinical communication may save costs. CONCLUSIONS: This rapid review showed an emerging body of literature on the use of digital clinical communication to improve families' and caregivers' involvement in the health management of children or young people. Further research with appropriate study designs and longer-term outcome measures should be encouraged. TRIAL REGISTRATION: PROSPERO CRD42016035467; http://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42016 035467(Archived by WebCite at http://www.webcitation.org/6vpgZU1FU).

Barriers to reporting of adverse drugs reactions: a cross sectional study among community pharmacists in United Kingdom.

BACKGROUND: Adverse Drug Reactions (ADRs) are a major public health problem. Prompt reporting of suspected ADRs is fundamental in the post-marketing surveillance of medicines and helps in ensuring medicine safety. However, fewer ADRs are reported in general and in particular by community pharmacists. There is limited knowledge about the factors which are preventing community pharmacists in the UK from reporting an ADR. OBJECTIVES: To identify the barriers to ADR reporting among community pharmacists practicing in the UK. METHODS: A cross sectional study using a 25-items questionnaire (both online and paper based) including 10 barriers to ADR reporting was conducted from 1st April 2012 to September 2012. Community pharmacists practicing in the West Midlands, UK, were approached for the participation in this study. Chi-Square and regression were applied to identify covariates for the barriers to ADR reporting. A significant value of 0.05 was assigned for analysis. RESULTS: Of the 230 invited community pharmacists, 138 pharmacists responded (response rate 60%). The median age of respondents was 31 years. All pharmacists reported that they would report both serious and mild ADRs from drugs with black triangle among children as well as adults. About 95% (n=131) of the pharmacists were familiar with the paper based ADR reporting system. Store-based pharmacists were more likely to be more confident about which ADRs to report [0.680, 95% Confidence Interval 0.43-3.59]. Lack of time 46.4% (n=64), and pharmacists perception that ADR is not serious enough to report (65.2%; n=90) were identified as barriers to ADR reporting. Majority 63.0% (n=87) of the pharmacists identified training and information about what to report and access to Information Technology (IT) (For example access to internet connection) 61.6% (n=85) as facilitators to ADR reporting process. CONCLUSION: Lack of time and ADRs considered not serious enough by pharmacists to report were barriers to ADR reporting. Further training and education about the types of ADRs to be reported can help to improve the reporting of ADRs.

Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review.

BACKGROUND: Tyrosinemia type 1 (TYR1) is a rare autosomal recessive disorder of amino acid metabolism that is fatal without treatment. With medication (nitisinone) and dietary restrictions outcomes are improved. We conducted a systematic review to investigate if treatment with nitisinone following screening provides better long-term outcomes than treatment with nitisinone following symptomatic detection. METHODS: We searched Web of Science, Medline, Pre-Medline, and Embase up to 23rd September 2016 for journal articles comparing clinical outcomes of TYR1 patients receiving earlier versus later nitisinone treatment. Two reviewers independently screened titles and abstracts, assessed full texts, and appraised study quality. Data extraction was performed by a single reviewer and checked by a second. RESULTS: We included seven articles out of 470 unique records identified by our search. The seven articles included four studies (three cohort studies and one cross-sectional study). Study sample sizes ranged from 17 to 148. There is consistent evidence that nitisinone is an effective treatment for TYR1, and some evidence that earlier treatment with nitisinone and dietary restrictions within the first one or 2 months of life is associated with reduced need for liver transplantation, lower rates of renal dysfunction, fewer neurological crises, and fewer, shorter hospital admissions compared to later treatment. However, study quality was moderate to weak, with high risk of confounding and applicability concerns to the screening context. We conducted post hoc analyses to address these issues. Results suggested an association between earlier treatment and fewer liver transplants (earlier treatment: 0% of 10-24 patients; later treatment: 25-60% of 4-15 patients), but no impact on neurological crises. We found no effect of treatment timing on mortality in either the primary or post hoc analyses. Post hoc analyses of other health-related outcomes were not possible because of sample size or reporting. CONCLUSIONS: There is some evidence from observational studies that earlier treatment with nitisinone might be beneficial but this is subject to bias. The applicability of our findings to the screening context or clinical practice is limited as not all early-treated patients were identified by screening and late-treated groups included patients born prior to the availability of nitisinone.

Barriers to reporting of adverse drugs reactions: a cross sectional study among community pharmacists in United Kingdom

Background: Adverse Drug Reactions (ADRs) are a major public health problem. Prompt reporting of suspected ADRs is fundamental in the post-marketing surveillance of medicines and helps in ensuring medicine safety. However, fewer ADRs are reported in general and in particular by community pharmacists. There is limited knowledge about the factors which are preventing community pharmacists in the UK from reporting an ADR. Objectives: To identify the barriers to ADR reporting among community pharmacists practicing in the UK. Methods: A cross sectional study using a 25-items questionnaire (both online and paper based) including 10 barriers to ADR reporting was conducted from 1st April 2012 to September 2012. Community pharmacists practicing in the West Midlands, UK, were approached for the participation in this study. Chi-Square and regression were applied to identify covariates for the barriers to ADR reporting. A significant value of 0.05 was assigned for analysis. Results: Of the 230 invited community pharmacists, 138 pharmacists responded (response rate 60%). The median age of respondents was 31 years. All pharmacists reported that they would report both serious and mild ADRs from drugs with black triangle among children as well as adults. About 95% (n=131) of the pharmacists were familiar with the paper based ADR reporting system. Store-based pharmacists were more likely to be more confident about which ADRs to report [0.680, 95% Confidence Interval 0.43-3.59]. Lack of time 46.4% (n=64), and pharmacists perception that ADR is not serious enough to report (65.2%; n=90) were identified as barriers to ADR reporting. Majority 63.0% (n=87) of the pharmacists identified training and information about what to report and access to Information Technology (IT) (For example access to internet connection) 61.6% (n=85) as facilitators to ADR reporting process. Conclusion: Lack of time and ADRs considered not serious enough by pharmacists to report were barriers to ADR reporting. Further training and education about the types of ADRs to be reported can help to improve the reporting of ADRs (AU)

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Comparison of a full systematic review versus rapid review approaches to assess a newborn screening test for tyrosinemia type 1.

BACKGROUND: Rapid reviews are increasingly used to replace/complement systematic reviews to support evidence-based decision-making. Little is known about how this expedited process affects results. OBJECTIVES: To assess differences between rapid and systematic review approaches for a case study of test accuracy of succinylacetone for detecting tyrosinemia type 1. METHODS: Two reviewers conducted an "enhanced" rapid review then a systematic review. The enhanced rapid review involved narrower searches, a single reviewer checking 20% of titles/abstracts and data extraction, and quality assessment using an unadjusted QUADAS-2. Two reviewers performed the systematic review with a tailored QUADAS-2. Post hoc analysis examined rapid reviewing with a single reviewer (basic rapid review). RESULTS: Ten papers were included. Basic rapid reviews would have missed 1 or 4 of these (dependent on which reviewer). Enhanced rapid and systematic reviews identified all 10 papers; one paper was only identified in the rapid review through reference checking. Two thousand one hundred seventy-six fewer title/abstracts and 129 fewer full texts were screened during the enhanced rapid review than the systematic review. The unadjusted QUADAS-2 generated more "unclear" ratings than the adjusted QUADAS-2 [29/70 (41.4%) versus 16/70 (22.9%)], and fewer "high" ratings [22/70 (31.4%) versus 42/70 (60.0%)]. Basic rapid reviews contained important inaccuracies in data extraction, which were detected by a second reviewer in the enhanced rapid and systematic reviews. CONCLUSIONS: Enhanced rapid reviews with 20% checking by a second reviewer may be an appropriate tool for policymakers to expeditiously assess evidence. Basic rapid reviews (single reviewer) have higher risks of important inaccuracies and omissions.

Test accuracy of drug and antibody assays for predicting response to antitumour necrosis factor treatment in Crohn's disease: a systematic review and meta-analysis.

OBJECTIVE: To present meta-analytic test accuracy estimates of levels of antitumour necrosis factor (anti-TNF) and antibodies to anti-TNF to predict loss of response or lack of regaining response in patients with anti-TNF managed Crohn's disease. METHODS: MEDLINE, Embase, the Cochrane Library and Science Citation Index were searched from inception to October/November 2014 to identify studies which reported 2×2 table data of the association between levels of anti-TNF or its antibodies and clinical status. Hierarchical/bivariate meta-analysis was undertaken with the user-written 'metandi' package of Harbord and Whiting using Stata V.11 software, for infliximab, adalimumab,anti-infliximab and anti-adalimumab levels as predictors of loss of response. Prevalence of Crohn's disease in included studies was meta-analysed using a random effects model in MetaAnalyst software to calculate positive and negative predictive values. The search was updated in January 2017. RESULTS: 31 studies were included in the review. Studies were heterogeneous with respect to the type of test used, criteria for establishing response and loss of response, population examined and results. Meta-analytic summary point estimates for sensitivity and specificity were 65.7% and 80.6% for infliximab trough levels and 56% and 79% for antibodies to infliximab, respectively. Pooled results for adalimumab trough levels and antibodies to adalimumab were similar. Pooled positive and negative predictive values ranged between 70% and 80% implying that between 20% and 30% of both positive and negative test results may be incorrect in predicting loss of response. CONCLUSION: The available evidence suggests that these tests have modest predictive accuracy for clinical status; direct test accuracy comparisons in the same population are needed. More clinical trial evidence from test-treat studies is required before the clinical utility of the tests can be reliably evaluated.

Skyrmion Knots in Frustrated Magnets.

A magnetic Skyrmion is a stable two-dimensional nanoparticle describing a localized winding of the magnetization in certain magnetic materials. Skyrmions are the subject of intense experimental and theoretical investigation and have potential technological spintronic applications. Here we show that numerical computations of frustrated magnets predict that Skyrmions can be tied into knots to form new stable three-dimensional nanoparticles. These stable equilibria of twisted loops of Skyrmion strings have an integer-valued topological charge, known as the Hopf charge, that counts the number of particles. Rings are formed for low values of this charge, but for higher values it is energetically favorable to form links and then knots. This computational study provides a novel impetus for future experimental work on these nanoknots and an exploration of the potential technological applications of three-dimensional nanoparticles encoding knotted magnetization.

Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis: systematic review and meta-analysis.

BACKGROUND: Timely and accurate identification of people with latent tuberculosis infection (LTBI) is important for controlling Mycobacterium tuberculosis (TB). There is no gold standard for diagnosis of LTBI. Screening tests such as interferon gamma release assays (IGRAs) and tuberculin skin test (TST) provide indirect and imperfect information. This systematic review compared two types of IGRAs QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT.TB with TST for identification of LTBI by predicting progression to a diagnosis of active TB in three subgroups: children, immunocompromised people, and those recently arrived from countries with high TB burden. METHODS: Cohort studies were eligible for inclusion. We searched MEDLINE, EMBASE, the Cochrane Library and other databases from December 2009 to June 2015. One reviewer screened studies, extracted data, and assessed risk of bias with cross checking by a second reviewer. Strength of association between test results and incidence of TB was summarised using cumulative incidence ratios (CIRs with 95% CIs). Summary effect measures: the ratio of CIRs (R-CIR) with 95% CIs. R-CIRs, were pooled using a random-effects model. Heterogeneity was assessed using Chi-squared and I2 statistics. RESULTS: Seventeen studies, mostly of moderate or high risk of bias (five in children, 10 in immunocompromised people, and two in those recently arrived) were included. In children, while in two studies, there was no significant difference between QFT-GIT and TST (≥5 mm) (pooled R-CIR = 1.11, 95% CI: 0.71, 1.74), two other studies showed QFT-GIT to outperform TST (≥10 mm) in identifying LTBI. In immunocompromised people, IGRA (T-SPOT.TB) was not significant different from TST (≥10 mm) for identifying LTBI, (pooled R-CIR = 1.01, 95% CI: 0.65, 1.58). The forest plot of two studies in recently arrived people from countries with high TB burden demonstrated inconsistent findings (high heterogeneity; I2 = 92%). CONCLUSIONS: Prospective studies comparing IGRA testing against TST on the progression from LTBI to TB were sparse, and these results should be interpreted with caution due to uncertainty, risk of bias, and unexplained heterogeneity. Population-based studies with adequate sample size and follow-up are required to adequately compare the performance of IGRA with TST in people at high risk of TB.

Newborn screening for Tyrosinemia type 1 using succinylacetone - a systematic review of test accuracy.

BACKGROUND: Tyrosinemia type 1 is an autosomal recessive disorder of amino acid metabolism. Without treatment, death in childhood is common. Treatment with nitisinone and dietary restrictions are associated with improved outcomes; some studies suggest better outcomes when treatment begins at an asymptomatic stage. Newborn screening allows for earlier identification, but there is uncertainty regarding the test accuracy of the current method: succinylacetone measurement in dried blood spots using tandem mass spectrometry. METHODS: We conducted a systematic review of literature published up to January 2016. Two reviewers independently assessed titles, abstracts, full texts, and conducted quality appraisals. A single reviewer extracted data, which was checked by a second reviewer. RESULTS: Ten studies provided test accuracy data: five studies reporting screening experiences and five case-control studies. Sensitivity (29 cases in total) and specificity (34,403 controls in total) were 100% in the case-control studies, but could not be calculated in the studies reporting screening experiences due to a lack of follow-up of screen-negative babies. Positive predictive values in the screening experience studies ranged from 66.7% (2 true positive cases, 1 false positive case from ~500,000 people screened) to 100% (8 true positive cases from 856,671 people screened); negative predictive values could not be calculated. Positive and negative predictive values cannot be calculated from case-control studies. CONCLUSIONS: Screening for Tyrosinemia type 1 using tandem mass spectrometry measurement of succinylacetone from dried blood spots appears to be promising. Confirmation of test accuracy data should be obtained from studies that include a two-year follow-up of individuals who screen negative.