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PLoS Medicine Mar 2022Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Global HIV treatment programs have sought to lengthen the interval between clinical encounters for people living with HIV (PLWH) who are established on antiretroviral treatment (ART) to reduce the burden of seeking care and to decongest health facilities. The overall effect of reduced visit frequency on HIV treatment outcomes is however unknown. We conducted a systematic review and meta-analysis to evaluate the effect of implementation strategies that reduce the frequency of clinical appointments and ART refills for PLWH established on ART.
METHODS AND FINDINGS
We searched databases between 1 January 2010 and 9 November 2021 to identify randomized controlled trials (RCTs) and observational studies that compared reduced (6- to 12-monthly) clinical consultation or ART refill appointment frequency to 3- to 6-monthly appointments for patients established on ART. We assessed methodological quality and real-world relevance, and used Mantel-Haenszel methods to generate pooled risk ratios (RRs) with 95% confidence intervals for retention, viral suppression, and mortality. We evaluated heterogeneity quantitatively and qualitatively, and overall evidence certainty using GRADE. Searches yielded 3,955 records, resulting in 10 studies (6 RCTs, 3 observational studies, and 1 study contributing observational and RCT data) representing 15 intervention arms with 33,599 adults (≥16 years) in 8 sub-Saharan African countries. Reduced frequency clinical consultations occurred at health facilities, while reduced frequency ART refills were delivered through facility or community pharmacies and adherence groups. Studies were highly pragmatic, except for some study settings and resources used in RCTs. Among studies comparing reduced clinical consultation frequency (6- or 12-monthly) to 3-monthly consultations, there appeared to be no difference in retention (RR 1.01, 95% CI 0.97-1.04, p = 0.682, 8 studies, low certainty), and this finding was consistent across 6- and 12-monthly consultation intervals and delivery strategies. Viral suppression effect estimates were markedly influenced by under-ascertainment of viral load outcomes in intervention arms, resulting in inconclusive evidence. There was similarly insufficient evidence to draw conclusions on mortality (RR 1.12, 95% CI 0.75-1.66, p = 0.592, 6 studies, very low certainty). For ART refill frequency, there appeared to be little to no difference in retention (RR 1.01, 95% CI 0.98-1.06, p = 0.473, 4 RCTs, moderate certainty) or mortality (RR 1.45, 95% CI 0.63-3.35, p = 0.382, 4 RCTs, low certainty) between 6-monthly and 3-monthly visits. Similar to the analysis for clinical consultations, although viral suppression appeared to be better in 3-monthly arms, effect estimates were markedly influence by under-ascertainment of viral load outcomes in intervention arms, resulting in overall inclusive evidence. This systematic review was limited by the small number of studies available to compare 12- versus 6-monthly clinical consultations, insufficient data to compare implementation strategies, and lack of evidence for children, key populations, and low- and middle-income countries outside of sub-Saharan Africa.
CONCLUSIONS
Based on this synthesis, extending clinical consultation intervals to 6 or 12 months and ART dispensing intervals to 6 months appears to result in similar retention to 3-month intervals, with less robust conclusions for viral suppression and mortality. Future research should ensure complete viral load outcome ascertainment, as well as explore mechanisms of effect, outcomes in other populations, and optimum delivery and monitoring strategies to ensure widespread applicability of reduced frequency visits across settings.
Topics: Adult; Anti-Retroviral Agents; Child; HIV Infections; Humans; Time Factors; Treatment Outcome; Viral Load
PubMed: 35316272
DOI: 10.1371/journal.pmed.1003959 -
Therapeutic Advances in Gastroenterology 2022Proton-pump inhibitors (PPIs) are widely prescribed as acid-suppression therapy. Some observational studies suggest that long-term use of PPIs is potentially associated... (Review)
Review
BACKGROUND
Proton-pump inhibitors (PPIs) are widely prescribed as acid-suppression therapy. Some observational studies suggest that long-term use of PPIs is potentially associated with certain adverse kidney outcomes. We conducted a systematic literature review to assess potential bias in non-randomized studies reporting on putative associations between PPIs and adverse kidney outcomes (acute kidney injury, acute interstitial nephritis, chronic interstitial nephritis, acute tubular necrosis, chronic kidney disease, and end-stage renal disease).
METHODS
We searched the medical literature within 10 years of 17 December 2020. Pre-specified criteria guided identification of relevant English language articles for assessment. Risk of bias on an outcome-specific basis was evaluated using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool by two independent reviewers.
RESULTS
Of 620 initially identified records, 26 studies met eligibility criteria and underwent risk of bias assessment. Nineteen studies were judged as having a moderate risk of bias for reported adverse kidney outcomes, while six studies were judged as having a serious risk of bias (mainly due to inadequate control of confounders and selection bias). We were unable to determine the overall risk of bias in two studies (one of which was assessed as having a moderate risk of bias for a different adverse kidney outcome) due to insufficient information presented. Effect estimates for PPIs in relation to adverse kidney outcomes varied widely (0.24-7.34) but associations mostly showed increased risk.
CONCLUSION
Using ROBINS-I, we found that non-randomized observational studies suggesting kidney harm by PPIs have moderate to serious risk of bias, making it challenging to establish causality. Additional high-quality, real-world evidence among generalizable populations are needed to better understand the relation between PPI treatment and acute and chronic kidney outcomes, accounting for the effects of varying durations of PPI treatment, self-treatment with over-the-counter PPIs, and potential critical confounders.
PubMed: 35173802
DOI: 10.1177/17562848221074183 -
Health Technology Assessment... Jan 2022In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In vitro fertilisation is a widely used reproductive technique that can be undertaken with or without intracytoplasmic sperm injection. The endometrial scratch procedure is an in vitro fertilisation 'add-on' that is sometimes provided prior to the first in vitro fertilisation cycle, but there is a lack of evidence to support its use.
OBJECTIVES
(1) To assess the clinical effectiveness, safety and cost-effectiveness of endometrial scratch compared with treatment as usual in women undergoing their first in vitro fertilisation cycle (the 'Endometrial Scratch Trial') and (2) to undertake a systematic review to combine the results of the Endometrial Scratch Trial with those of previous trials in which endometrial scratch was provided prior to the first in vitro fertilisation cycle.
DESIGN
A pragmatic, multicentre, superiority, open-label, parallel-group, individually randomised controlled trial. Participants were randomised (1 : 1) via a web-based system to receive endometrial scratch or treatment as usual using stratified block randomisation. The systematic review involved searching electronic databases (undertaken in January 2020) and clinicaltrials.gov (undertaken in September 2020) for relevant trials.
SETTING
Sixteen UK fertility units.
PARTICIPANTS
Women aged 18-37 years, inclusive, undergoing their first in vitro fertilisation cycle. The exclusion criteria included severe endometriosis, body mass index ≥ 35 kg/m and previous trauma to the endometrium.
INTERVENTIONS
Endometrial scratch was undertaken in the mid-luteal phase of the menstrual cycle prior to in vitro fertilisation, and involved inserting a pipelle into the cavity of the uterus and rotating and withdrawing it three or four times. The endometrial scratch group then received usual in vitro fertilisation treatment. The treatment-as-usual group received usual in vitro fertilisation only.
MAIN OUTCOME MEASURES
The primary outcome was live birth after completion of 24 weeks' gestation within 10.5 months of egg collection. Secondary outcomes included implantation, pregnancy, ectopic pregnancy, miscarriage, pain and tolerability of the procedure, adverse events and treatment costs.
RESULTS
One thousand and forty-eight (30.3%) women were randomised to treatment as usual ( = 525) or endometrial scratch ( = 523) and were followed up between July 2016 and October 2019 and included in the intention-to-treat analysis. In the endometrial scratch group, 453 (86.6%) women received the endometrial scratch procedure. A total of 494 (94.1%) women in the treatment-as-usual group and 497 (95.0%) women in the endometrial scratch group underwent in vitro fertilisation. The live birth rate was 37.1% (195/525) in the treatment-as-usual group and 38.6% (202/523) in the endometrial scratch group: an unadjusted absolute difference of 1.5% (95% confidence interval -4.4% to 7.4%; = 0.621). There were no statistically significant differences in secondary outcomes. Safety events were comparable across groups. No neonatal deaths were recorded. The cost per successful live birth was £11.90 per woman (95% confidence interval -£134 to £127). The pooled results of this trial and of eight similar trials found no evidence of a significant effect of endometrial scratch in increasing live birth rate (odds ratio 1.03, 95% confidence interval 0.87 to 1.22).
LIMITATIONS
A sham endometrial scratch procedure was not undertaken, but it is unlikely that doing so would have influenced the results, as objective fertility outcomes were used. A total of 9.2% of women randomised to receive endometrial scratch did not undergo the procedure, which may have slightly diluted the treatment effect.
CONCLUSIONS
We found no evidence to support the theory that performing endometrial scratch in the mid-luteal phase in women undergoing their first in vitro fertilisation cycle significantly improves live birth rate, although the procedure was well tolerated and safe. We recommend that endometrial scratch is not undertaken in this population.
TRIAL REGISTRATION
This trial is registered as ISRCTN23800982.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 26, No. 10. See the NIHR Journals Library website for further project information.
Topics: Adolescent; Adult; Female; Humans; Pregnancy; Young Adult; Birth Rate; Endometrium; Fertilization in Vitro; Live Birth; Pregnancy Rate
PubMed: 35129113
DOI: 10.3310/JNZT9406 -
Reproduction & Fertility Jan 2021Up to 28% of endometriosis patients do not get pain relief from therapeutic laparoscopy but this subgroup is not defined.
BACKGROUND
Up to 28% of endometriosis patients do not get pain relief from therapeutic laparoscopy but this subgroup is not defined.
OBJECTIVES
To identify any prognostic patient-specific factors (such as but not limited to patients' type or location of endometriosis, sociodemographics and lifestyle) associated with a clinically meaningful reduction in post-surgical pain response to operative laparoscopic surgery for endometriosis.
SEARCH STRATEGY
PubMed, Cochrane and Embase databases were searched from inception to 19 May 2020 without language restrictions. Backward and forward citation tracking was used.
SELECTION CRITERIA DATA COLLECTION AND ANALYSIS
Cohort studies reporting prognostic factors, along with scores for domains of pain associated with endometriosis before and after surgery, were included. Studies that compared surgeries, or laboratory tests, or outcomes without stratification were excluded. Results were synthesised but variation in study designs and inconsistency of outcome reporting precluded us from doing a meta-analysis.
MAIN RESULTS
Five studies were included. Quality assessment using the Newcastle-Ottawa scale graded three studies as high, one as moderate and one as having a low risk of bias. Four of five included studies separately reported that a relationship exists between more severe endometriosis and stronger pain relief from laparoscopic surgery.
CONCLUSION
Currently, there are few studies of appropriate quality to answer the research question. We recommend future studies report core outcome sets to enable meta-analysis.
LAY SUMMARY
Endometriosis is a painful condition caused by displaced cells from the lining of the womb, causing inflammation and scarring inside the body. It affects 6-10% of women and there is no permanent cure. Medical and laparoscopic surgical treatments are available, but about 28% of patients do not get the hoped-for pain relief after surgery. Currently, there is no way of predicting who gets better and who does not. We systematically searched the world literature to establish who may get better, in order to improve counselling when women choose treatment options. We identified five studies of variable quality showing: More complex disease (in specialist hands) responds better to surgery than less, but more studies needed.
Topics: Endometriosis; Female; Humans; Laparoscopy; Pelvic Pain; Uterus
PubMed: 35128434
DOI: 10.1530/RAF-20-0057 -
Antimicrobial Resistance and Infection... Jan 2022Despite clear evidence of benefits in acute-care hospitals, controversy over the effectiveness of IPC measures for MDROs is perceptible and evidence-based practice has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite clear evidence of benefits in acute-care hospitals, controversy over the effectiveness of IPC measures for MDROs is perceptible and evidence-based practice has not been established.
OBJECTIVE
To investigate the effects of IPC interventions on MDRO colonization and infections in LTCFs.
DATA SOURCES
Ovid MEDLINE, EMBASE, and CINAHL from inception to September 2020.
ELIGIBILITY CRITERIA
Original and peer-reviewed articles examining the post-intervention effects on MDRO colonization and infections in LTCFs.
INTERVENTIONS
(i) Horizontal interventions: administrative engagement, barrier precautions, education, environmental cleaning, hand hygiene, performance improvement, and source control; and (ii) vertical intervention: active surveillance plus decolonization.
STUDY APPRAISAL AND SYNTHESIS
We employed a random-effects meta-analysis to estimate the pooled risk ratios (pRRs) for methicillin-resistant Staphylococcus aureus (MRSA) colonization by intervention duration; and conducted subgroup analyses on different intervention components. Study quality was assessed using Cochrane risk of bias tools.
RESULTS
Of 3877 studies identified, 19 were eligible for inclusion (eight randomized controlled trials (RCTs)). Studies reported outcomes associated with MRSA (15 studies), vancomycin-resistant Enterococci (VRE) (four studies), Clostridium difficile (two studies), and Gram-negative bacteria (GNB) (two studies). Eleven studies were included in the meta-analysis. The pRRs were close to unity regardless of intervention duration (long: RR 0.81 [95% CI 0.60-1.10]; medium: RR 0.81 [95% CI 0.25-2.68]; short: RR 0.95 [95% CI 0.53-1.69]). Vertical interventions in studies with a small sample size showed significant reductions in MRSA colonization while horizontal interventions did not. All studies involving active administrative engagement reported reductions. The risk of bias was high in all but two studies.
CONCLUSIONS
Our meta-analysis did not show any beneficial effects from IPC interventions on MRSA reductions in LTCFs. Our findings highlight that the effectiveness of interventions in these facilities is likely conditional on resource availability-particularly decolonization and barrier precautions, due to their potential adverse events and uncertain effectiveness. Hence, administrative engagement is crucial for all effective IPC programmes. LTCFs should consider a pragmatic approach to reinforce standard precautions as routine practice and implement barrier precautions and decolonization to outbreak responses only.
Topics: Drug Resistance, Multiple, Bacterial; Humans; Infection Control; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections
PubMed: 35033198
DOI: 10.1186/s13756-021-01044-0 -
Journal of Global Health 2021Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly...
BACKGROUND
Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required.
METHODS
A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted.
RESULTS
179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions.
CONCLUSIONS
Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts.
Topics: Developing Countries; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Pregnancy; Premature Birth; Resuscitation; Stillbirth
PubMed: 35003711
DOI: 10.7189/jogh.11.04050 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
Implementation Science Communications Dec 2021Self-collection of samples for HPV testing may increase women's access to cervical cancer screening in low- and middle-income settings. However, implementation remains... (Review)
Review
INTRODUCTION
Self-collection of samples for HPV testing may increase women's access to cervical cancer screening in low- and middle-income settings. However, implementation remains poor in many regions. The purpose of this systematic review was to examine implementation data from randomized controlled trials evaluating human papillomavirus (HPV) self-collection testing among women in sub-Saharan Africa using the RE-AIM (Reach, Efficacy/Effectiveness, Adoption, Implementation, and Maintenance) framework.
METHODS
We searched four electronic databases (PubMed, CINAHL, Web of Science, and Global Health) for pragmatic randomized controlled trials that promote HPV self-collection among women in sub-Saharan Africa. Study selection and data extraction were conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) checklist. Two researchers independently extracted information from each article using a RE-AIM data extraction tool. The reporting of RE-AIM dimensions was summarized and synthesized across included interventions.
RESULTS
We identified 2008 citations, and eight studies were included. These reported on five unique interventions. The five interventions were conducted in five countries: Cameroon, Ethiopia, Kenya, Nigeria, and Uganda. Intervention reach (80%) was the most commonly reported RE-AIM dimension, followed by adoption (56%), efficacy/effectiveness (52%), implementation (47%), and maintenance (0%). All the interventions described increased uptake of HPV testing among study participants (effectiveness). However, the majority of the studies focused on reporting internal validity indicators such as inclusion criteria (100%) and exclusion criteria (100%), and few reported on external validity indicators such as participation rate (40%), intervention cost (40%), staff selection (20%), and cost of maintenance (0%).
CONCLUSIONS
Our review highlights the under-reporting of external validity indicators such as participation rate, intervention, and maintenance costs in studies of self-collection for HPV testing among women in SSA. Future research should focus on including factors that highlight internal validity factors and external validity factors to develop a greater understanding of ways to increase not only reach but also implementation and long-term maintenance of these interventions. Such data may advance the translation of HPV interventions into practice and reduce health disparities in SSA. Findings highlight the need for innovative tools such as participatory learning approaches or open challenges to expand knowledge and assessment of external validity indicators to ultimately increase the uptake of HPV testing among women in SSA.
PubMed: 34911573
DOI: 10.1186/s43058-021-00243-5 -
Cells Oct 2021There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising...
Assessing Creatine Supplementation for Neuroprotection against Perinatal Hypoxic-Ischaemic Encephalopathy: A Systematic Review of Perinatal and Adult Pre-Clinical Studies.
UNLABELLED
There is an important unmet need to develop interventions that improve outcomes of hypoxic-ischaemic encephalopathy (HIE). Creatine has emerged as a promising neuroprotective agent. Our objective was to systematically evaluate the preclinical animal studies that used creatine for perinatal neuroprotection, and to identify knowledge gaps that need to be addressed before creatine can be considered for pragmatic clinical trials for HIE.
METHODS
We reviewed preclinical studies up to 20 September 2021 using PubMed, EMBASE and OVID MEDLINE databases. The SYRCLE risk of bias assessment tool was utilized.
RESULTS
Seventeen studies were identified. Dietary creatine was the most common administration route. Cerebral creatine loading was age-dependent with near term/term-equivalent studies reporting higher increases in creatine/phosphocreatine compared to adolescent-adult equivalent studies. Most studies did not control for sex, study long-term histological and functional outcomes, or test creatine post-HI. None of the perinatal studies that suggested benefit directly controlled core body temperature (a known confounder) and many did not clearly state controlling for potential study bias.
CONCLUSION
Creatine is a promising neuroprotective intervention for HIE. However, this systematic review reveals key knowledge gaps and improvements to preclinical studies that must be addressed before creatine can be trailed for neuroprotection of the human fetus/neonate.
Topics: Aging; Animals; Creatine; Dietary Supplements; Female; Hypoxia-Ischemia, Brain; Male; Neuroprotection; Publication Bias; Risk; Survival Analysis; Time Factors
PubMed: 34831126
DOI: 10.3390/cells10112902 -
Journal of Clinical Medicine Oct 2021(1) Background: Acute neck pain is common and usually managed by medication and/or manual therapy. General practitioners (GPs) hesitate to refer to manual therapy due to... (Review)
Review
(1) Background: Acute neck pain is common and usually managed by medication and/or manual therapy. General practitioners (GPs) hesitate to refer to manual therapy due to uncertainty about the effectiveness and adverse events (AEs); (2) Method: To review original randomized controlled trials (RCTs) assessing the effect of spinal manipulative therapy (SMT) for acute neck pain. Data extraction was done in duplicate and formulated in tables. Quality and evidence were assessed using the Cochrane Back and Neck (CBN) Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, respectively; (3) Results: Six studies were included. The overall pooled effect size for neck pain was very large -1.37 (95% CI, -2.41, -0.34), favouring treatments with SMT compared with controls. A single study that showed that SMT was statistically significantly better than medicine (30 mg ketorolac im.) one day post-treatment, ((-2.8 (46%) (95% CI, -2.1, -3.4) vs. -1.7 (30%) (95% CI, -1.1, -2.3), respectively; = 0.02)). Minor transient AEs reported included increased pain and headache, while no serious AEs were reported; (4) Conclusions: SMT alone or in combination with other modalities was effective for patients with acute neck pain. However, limited quantity and quality, pragmatic design, and high heterogeneity limit our findings.
PubMed: 34768531
DOI: 10.3390/jcm10215011