Sarah Dawson

Background: Liquid biopsies offer a minimally invasive approach for early glioma detection. However, potential non-blood biomarkers in urine and CSF are under-researched. While urine is easier to sample and has fewer proteins/cells, CSF may yield higher detection rates due to its proximity to the glioma. This systematic review evaluates non-blood liquid biopsy biomarkers (proteins, metabolites, cell-free DNA, and miRNA) in urine and CSF for early glioma detection. Methods: Three electronic databases (MEDLINE, Embase, and BIOSIS) were searched from inception to September 2024. Studies which assessed urine- or CSF-derived biomarkers as a means of identifying glioma patients were included. The primary outcomes of interest were measures of diagnostic test accuracy (specificity, sensitivity, positive predictive value, negative predictive value and area under the ROC curve). QUADAS-2 was used to assess risk of bias in included studies. Results: We extracted data from 20 studies (669 glioma patients and 597 controls) which met the inclusion criteria. Five of the included studies investigated urine-derived biomarkers, and 15 investigated CSF-derived biomarkers. Meta-analysis was not possible due to the heterogeneous nature of biomarkers collected, analysis methods, and differences in patient demographics. Conclusions: Conclusions are limited by the paucity of studies and small sample sizes. These limitations highlight the need for well-designed, adequately powered studies to evaluate the diagnostic utility of urine and CSF for glioma liquid biopsies.

Background: This WHO-commissioned series of systematic reviews synthesised low- and middle-income country (LMIC) evidence on fractures and bone mineral density (BMD): prevalence, risk factors, fracture prevention, adverse effects of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP), in people living with HIV (PLHIV) or needing PrEP. Methods: We searched MEDLINE, Embase, SciELO and WHO Global Index Medicus (to 17-02-2026) for observational studies and RCTs in adults from LMICs. We employed pairwise and network meta-analyses (NMAs), component NMA and meta-regression; assessing heterogeneity, risk of bias; and GRADE evidence certainty. Findings: Thirty-eight studies reported fracture and 24 BMD loss (47,620 participants); most included adults <50 years (79% fracture and 92% BMD). Pooled fracture prevalence was 10%[95%CI 5-16%], with high heterogeneity (20 studies; n=2779, 260 fractures). Meta-regression indicated higher prevalence with radiographic fracture ascertainment (25%[14-39%]), longer HIV duration, and higher GINI coefficients. Associations of HIV (with ART) vs. HIV-negative were: more fractures (OR 2·06[1·17,3·61]; 2 studies, 63 fractures, n=659, low-certainty) and greater BMD loss, varying by ART type, e.g. tenofovir disoproxil fumarate (TDF)-ART vs. HIV-negative: mean difference (MD) -3·50%[-4·06,-2·95%] over 12-months (4 studies; n=577; moderate-certainty). In PLHIV, risk factors for poor bone outcomes included age, smoking, HIV-disease markers, protease inhibitors, and a clear gradient from no-ART to TDF-ART.In trials, TDF-containing PrEP and ART indicated greater fracture/BMD loss vs. placebo and non-TDF-ART, respectively. NMA of ten PrEP RCTs (n=31,651) suggests increased fracture risk for TDF-monotherapy vs placebo (RR 1·27[0·97,1·67]; low-certainty). TDF-PrEP vs. placebo conferred BMD loss: MD −0·74%[-1·28,-0·20%] (3 RCTs, n=929, low-certainty). In PLHIV, TDF-ART vs. non-TDF-ART produced MD -1·69%[-2·16,-1·21%] (6 RCTs, n=2331, moderate-certainty). Interpretation: Fractures are common in PLHIV in LMICs, including younger people. Evidence certainty is sometimes low, especially for fractures, but synthesis across diverse reviews demonstrates consistent associations between TDF-ART and BMD loss/fractures, which should inform global health policy (PROSPERO CRD42024587101).

Antenatal magnesium sulfate (MgSO ₄ ) and antenatal steroids (ANS) are evidence‐based interventions that reduce risk of cerebral palsy and respiratory complications in preterm babies. They are recommended in clinical guidelines internationally. However, we have limited information on how well they are being implemented. The present study is a secondary data analysis and review using routine neonatal data on babies born 24–32 weeks' gestation, from hospitals in the international Vermont Oxford Network (VON) dataset. It is supplemented with UK National Neonatal Research Database data, and a literature review. We describe international use of antenatal MgSO ₄ and ANS, with focus on differences between high (HIC) versus middle‐income (MIC) countries. VON data from 2024 on 45 619 infants across 1111 centers from the UK, Ireland, Austria, Switzerland, Italy, US, UAE, Brazil, South Africa, and India were included. Ireland and the UK had the highest rates of MgSO ₄ administration (>80%); South Africa and the UAE had the lowest (33.6%, 44.5%). There was a significant difference by income status (mean 74.8% in HICs vs. 49.4% in MICs). This disparity does not appear to have reduced over time. ANS were used more, with less variation. The supplementary literature review (10 studies reporting on 288 631 infants) found comparable treatment rates to those reported in VON. Use of antenatal MgSO ₄ and ANS varies considerably across countries. Uptake is significantly lower in these MICs, but variation is high even between these HICs. Further work should prioritize understanding why differences exist, and what can be done to make these key antenatal interventions more globally equitable.

Background: Childhood obesity is a major public health concern worldwide, yet the best way to prevent it remains unknown. Objective(s): To determine what types of intervention strategy are most effective at preventing the development of obesity in children aged 5–18 years, as measured by change in body mass index, and to determine whether interventions work differentially in children with different characteristics associated with inequities. Design: Systematic reviews and statistical evidence syntheses. Eligibility criteria: Randomised controlled trials of dietary and/or activity interventions that aimed to prevent overweight or obesity in children and young people aged 5–18 years and reported outcomes at least 12 weeks after baseline. Non-randomised evidence was identified through an overview of systematic reviews. Sources of inequity of interest were those defined by the PROGRESS (place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital) acronym: place, race/ethnicity, occupation (of parents), gender/sex, religion, education (of parents), socioeconomic status and social capital. Data sources: Updating of an existing Cochrane Review, searching bibliographic databases up to February 2023, including MEDLINE, EMBASE, PsycInfo® (American Psychological Association, Washington, DC, USA) and Cochrane Central Register of Controlled Trials on the Cochrane Library, international trial registers and grey literature databases, and examining reference lists. Results subgrouped by inequity factors were sought directly from trialists. Review methods: Cochrane Reviews followed standard Cochrane procedures. The main statistical synthesis was informed by a novel analytic framework developed iteratively through discussions with children and young people, schoolteachers and public health professionals. Methodology was developed to analyse the data using multilevel metaregression. To examine the impact of inequity factors, we performed a two-stage meta-analysis of interactions, based on subgroup-level aggregate data collected directly from the trialists. We collected available information on intervention costs. Results: We included 172 trials in ages 5–11 and 74 in ages 12–18. In the main synthesis, of 204 trials from both reviews, we found interventions were effective on average (mean difference in standardised body mass index −0.037, 95% credible interval −0.053 to −0.022, which would correspond to a reduction in a proportion of 2.3% with obesity to a proportion of approximately 2.1%). Larger effects were associated with physical activity rather than dietary interventions, after 12 months of follow-up and in the older age group. The overview of non-randomised evidence included 24 systematic reviews, yielding mixed results. The investigation of inequity did not identify substantial differences in effectiveness according to place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital characteristics, and there was very limited information about costs. Limitations: We were able to examine only the interventions that had been evaluated in studies identified for inclusion in the systematic reviews, which does not cover all possible intervention approaches. Conclusions: Interventions to prevent obesity in children aged 5–18 have a small beneficial effect on body mass index on average but with considerable variation. A novel re-analysis of existing randomised trials failed to identify general intervention characteristics driving this variation. No evidence was identified to suggest that interventions increase (or decrease) health inequities. Future work: Future studies of the effects of interventions to prevent childhood obesity should routinely collect baseline characteristics around potential inequities. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131572.

Background and Aims: Cocaine use disorder (CUD) is an increasingly widespread concern worldwide. Various pharmacological treatments have been investigated for CUD, but their efficacy remains unclear, and none have been licensed for treatment. Therefore, we assessed the comparative effectiveness, safety, and acceptability of pharmacological interventions for the treatment of CUD and prevention of relapse. Design: Systematic review and network meta-analyses of double-blind randomized controlled trials (RCTs). PROSPERO (CRD42024596434). We assessed risk of bias using the Cochrane Risk of Bias 2 tool and certainty of evidence was assessed using the Confidence in Network Meta-analysis framework. Setting: Any in/outpatient setting, with no restriction on geographic location. Participants: Adults with diagnosed CUD. Participants with co-occurring substance use disorders and/or common mental health conditions were eligible. Interventions: Pharmacologicalinterventions specifically tested for the treatment of CUD with a minimum follow-up of 4 weeks. Measurements: We assessed 12 effectiveness, three acceptability, and two safety outcomes. Our primary outcomes were continuous abstinence, point abstinence, dropout for any reason, and serious adverse events. We also examined longest duration of continuous abstinence, extent of cocaine use, craving, severity of dependence, dropout due to adverse events, adherence, and mortality. Findings: We included 218 reports of 163 studies (14871 participants) assessing 89 unique medications, grouped into 8 categories. Most study results had some concerns or high risk of bias, and the results of syntheses were generally judged to be very low certainty evidence. As such, the findings ought to be interpreted with caution. No single treatment type showed consistent beneficial effects across all effectiveness outcomes and there was limited evidence that results varied by intervention type or presence of co-occurring comorbidity. Conclusions: Despite continued work in this area, effective pharmacological treatments for CUD remain elusive.

Background: Housebound patients are an under-researched group who face challenges accessing primary health care and have complex needs. There is no consensus definition of ‘housebound’, hindering research. Aim: To develop a definition of housebound. Design & setting: A mixed-methods study using consensus methodology was conducted in the UK. Method: The study had the following parts: (i) a systematic review to examine how housebound was defined within UK literature; (ii) interviews to explore views of housebound people and carers ( n = 12); (iii) a consensus exercise with health and social care professionals ( n = 14) to agree a definition. An evidence summary was developed for each definition, combining review and interview data. A two-stage RAND/UCLA Appropriateness Method was used, with consensus defined as a median score ≥7/9 for clarity and appropriateness. Results: In total, 847 titles and abstracts were screened, and 413 articles underwent full-text review. Fifty-two definitions were identified, grouped under the following five themes: unable to attend the surgery; unable to leave the house; unable to leave the house without assistance; self-report of being housebound; and recorded as housebound on healthcare records. Subcategories of housebound included fully or semi, temporarily or permanently, and blockbound, housebound, chairbound, or bedbound. Six definitions met the top-scoring criteria, and a final definition was agreed: ‘Someone who is unable to leave their home or who requires significant assistance to do so. This may be due to illness, frailty, disability, surgery, mental ill health, or nearing the end of life.’ Conclusion: Our consensus definition can be used in UK research and may help policymakers and providers — within and outside the UK — evaluate and develop healthcare services for housebound patients.

Background: When monitoring long-term conditions, both over- and undertesting can risk patient harm and increase healthcare costs. Aim: To evaluate the evidence base for type 2 diabetes mellitus (T2DM) monitoring tests and develop methods for creating evidence-based testing strategies. Design and setting: Rapid reviews were conducted and a consensus process then used to evaluate the evidence base within primary care settings. Method: The authors identified tests that are recommended or used commonly to monitor T2DM. Filtering questions were created to examine the rationale for use of each test, which were answered by stepwise rapid reviews of evidence cited by guidelines, systematic reviews, and individual studies. A consensus group of patient representatives and clinicians voted whether tests should be included or excluded based on the evidence or whether further evidence was needed. Results: Of 15 tests, only haemoglobin A1c, to monitor disease progression and treatment response, and estimated glomerular filtration rate, to detect chronic kidney disease, have a strong evidence base. Based on available evidence and consensus group feedback, routinely testing for fructosamine to monitor disease progression; thyroid function, vitamin B12, ferritin, folate, clotting, bone profile, C-reactive protein, erythrocyte sedimentation rate, and B-type natriuretic peptide; and liver function for adverse treatment effects of metformin was deemed unnecessary. The study found insufficient evidence for lipids and haemoglobin to screen for secondary conditions, and for vitamin B12 to screen for adverse effects in those taking metformin. Conclusion: The study found that the evidence base for most T2DM monitoring tests is weak or absent. Clinicians should avoid non-evidence-based tests unless there are additional clinical indications for testing. Standardised evidence-based testing panels for T2DM and other long-term conditions could reduce unnecessary testing.

Aim: To evaluate the effectiveness, safety and cost‐effectiveness of psychosocial interventions for cannabis use disorder (CUD).Methods: A systematic review of randomized controlled trials (RCTs; PROSPERO protocol CRD42024553382) of psychosocial interventions for CUD lasting >4 sessions, delivered synchronously, to individuals with CUD aged ≥16 years, in inpatient, outpatient or community‐based settings. We searched databases (MEDLINE/PsycInfo/Cochrane CENTRAL) to 12 June 2024. We assessed results using Risk of Bias 2 and conducted pairwise meta‐analyses. Primary outcomes were continuous‐ and point‐abstinence and withdrawal intensity at the end of treatment, treatment completion and adverse events.Results: We included 22 RCTs (3304 participants). Relative to an inactive/non‐specific comparator, cognitive‐behavioural therapy with motivation enhancement (MET‐CBT) increased point abstinence [odds ratio (OR) = 18.27; 95% confidence interval (9.00−37.07)] and continuous abstinence [OR = 2.72; (1.20−6.19)], but reduced treatment completion [OR = 0.53; (0.35−0.85)]. Dialectical behavioural/acceptance and commitment therapy increased point abstinence versus inactive/non‐specific comparator [OR = 4.34; (1.74−10.80)]. The effect of MET‐CBT plus affect management versus MET‐CBT on point abstinence was OR = 7.85 (0.38−163.52). The effect of MET‐CBT plus abstinence‐based contingency management versus MET‐CBT on point abstinence was OR = 3.78 (0.83−17.25), and on continuous abstinence OR = 1.81 (0.61−5.41). For MET‐CBT plus abstinence‐contingency management versus MET‐CBT plus attendance‐contingency management, the effect on point abstinence was OR = 1.61 (0.72−3.60), and on continuous abstinence OR = 2.04 (0.75−5.58). The effect of community reinforcement on point abstinence was OR = 0.29 (0.04−1.90) versus MET‐CBT, and on continuous abstinence OR = 47.36 (16.00−140.21) versus non‐specific comparator. Interventions other than MET‐CBT may not affect treatment completion. No adverse events were reported. No study reported withdrawal intensity. Two economic evaluations reported higher costs for more complex interventions and contingency management.Conclusions: Cognitive‐behavioural therapy with motivation enhancement and dialectical behavioural/acceptance and commitment therapy may increase abstinence among people with cannabis use disorder relative to an inactive/non‐specific comparator. The conclusions remain tentative due to low‐ to very low‐certainty evidence and the small number of studies.

Main problem: There is substantial UK variation regarding which blood tests people receive for routine monitoring of stage 3 chronic kidney disease (CKD3) in primary care, suggesting that many people are not receiving optimal care. This study aimed to develop evidence-based testing panels for CKD3. Methods: We considered blood tests used commonly or recommended in CKD3 guidelines, identifying the rationale for each test and then applying a series of filtering questions (e.g. ‘can the GP do anything in response to an abnormal result?’) to identify whether tests should be included in the testing panel. Each question was answered by stepwise rapid evidence reviews. A consensus group, consisting of patient representatives and clinicians, voted on whether tests should be included based on the evidence. If tests had insuficient evidence, additional evidence was collected through rapid reviews or routine data analysis and voted on in a second consensus meeting. Results: There was good evidence for, and consensus supporting, routinely testing eGFR, haemoglobin, and HbA1c; and not routinely testing urea, lipids, vitamin B12, ferritin, folate, liver function, potassium, sodium, vitamin D, calcium, thyroid function, clotting, C-reactive protein, erythrocyte sedimentation rate, and B-type natriuretic peptide. Once on stable treatment, patients on statins do not need additional monitoring tests and patients on ACE-1 or ARB only need potassium monitoring. Conclusions: In contrast to current guidelines, our findings suggest that CKD3 patients should only be routinely ofered eGFR, HbA1c and haemoglobin monitoring. Implementing these recommendations could reduce testing variation in CKD3 patients and reduce costs. Lay summary: Patients with chronic kidney disease are often followed up by their GP. At regular monitoring appointments, blood and urine tests are done to determine whether a change in management is needed, such as adjusting medications. However, which tests are needed at these appointments is not standardised and depending on where you live, the tests that you get may difer because of diferences in local practices. Here, we reviewed the evidence for blood tests that are currently used for patients with chronic kidney disease, and we found that for many tests there is little or no evidence that they are beneficial. We only found good evidence for regular testing of eGFR to test renal function, HbA1c to detect diabetes, and haemoglobin to detect anaemia. Avoiding unnecessary tests is important to prevent overdiagnosis, overtreatment, patient anxiety, and to ensure that resources are focused on efective, evidence-based care.

Objective: To assess whether relaxation and stress management techniques are useful in reducing blood pressure in individuals with hypertension and prehypertension. Design: Systematic review and network meta-analysis. Data sources: Medline, PsycInfo, and CENTRAL (Cochrane Central Register of Controlled Trials) from inception to 23 February 2024, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from inception to 27 February 2024. Eligibility criteria for selecting studies: Studies published in English of adults with hypertension (blood pressure ≥140/90 mm Hg) or prehypertension (blood pressure ≥120/80 mm Hg but <140/90 mm Hg). Studies that compared non-pharmacological interventions used to promote relaxation or reduce stress with each other, or with a control group (eg, no intervention, waiting list, or standard care). Where possible, network meta-analysis was used to compare the efficacy of the different interventions. Studies were assessed with the risk of bias 2 tool (RoB2), and those at high risk of bias were excluded from the primary analysis. The certainty of the evidence was assessed with CINeMA (Confidence in Network Meta-Analysis) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: 182 studies were included (166 for hypertension and 16 for prehypertension). Results from a random effects network meta-analysis showed that, at short term follow-up (≤3 months), most relaxation interventions appeared to have a beneficial effect on systolic and diastolic blood pressure for individuals with hypertension. Between study heterogeneity was moderate (τ=2.62-4.73). Compared with a passive comparator (ie, no intervention, waiting list, or usual care), moderate reductions in systolic blood pressure were found for breathing control (mean difference −6.65 mm Hg, 95% credible interval −10.39 to −2.93), meditation (mean difference −7.71 mm Hg, −14.07 to −1.29), meditative movement (including tai chi and yoga, mean difference −9.58 mm Hg, −12.95 to −6.17), mindfulness (mean difference −9.90 mm Hg, −16.44 to −3.53), music (mean difference −6.61 mm Hg, −11.62 to −1.56), progressive muscle relaxation (mean difference −7.46 mm Hg, −12.15 to −2.96), psychotherapy (mean difference −9.83 mm Hg, −16.24 to −3.43), and multicomponent interventions (mean difference −6.78 mm Hg, −11.59 to −1.99). Reductions were also seen in diastolic blood pressure. Few studies conducted follow-up for more than three months, but effects on blood pressure seemed to lessen over time. Limited data were available for prehypertension; only two studies compared short term follow-up of relaxation therapies with a passive comparator, and the effects on systolic blood pressure were small (mean difference −3.84 mm Hg, 95% credible interval −6.25 to −1.43 for meditative movement; mean difference −0.53 mm Hg, −2.03 to 0.97 for multicomponent intervention). The certainty of the evidence was considered to be very low based on the CINeMA framework, owing to the risk of bias in the primary studies, potential publication bias, and imprecision in the effect estimates. Conclusions: The results of the study indicated that relaxation and stress management techniques might have beneficial short term effects on blood pressure for people with hypertension, but the effectiveness of these interventions is still uncertain. Future studies should ensure rigorous methods are used to minimise the risk of bias, and a longer duration of follow-up to establish whether these effects persist. Systematic review registration: PROSPERO CRD42023469128