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Cureus Jan 2023Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant... (Review)
Review
Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant impact on the United States healthcare system. It not only has a toll on the healthcare spending but also contributes to significant morbidity and mortality. Benzodiazepines are considered first line in the treatment of AWS. Since patients with alcohol use disorder have downregulated gamma aminobutyric acid (GABA) receptors, this often leads to benzodiazepine resistance. Phenobarbital is also used in the management of alcohol withdrawal syndrome. Here we present a systematic review and meta-analysis of the efficacy and safety of the drug. We conducted an electronic database search for relevant studies published between the inception of the project and November 20, 2022, in three databases, including Medline/PubMed, Embase, and Cochrane Library. Our study included all original studies with prime focus on the baseline characteristics of patients admitted to the intensive care unit (ICU) for alcohol withdrawal syndrome and management/monitoring protocol implemented for its treatment. The primary outcomes that were the focus of our study consisted of changes in the length of hospital stay, length of ICU stay, and changes in scoring systems (for alcohol withdrawal assessment and monitoring) following the implementation of phenobarbital. The secondary outcomes included complications such as intubation and mortality. Based on our analysis, the mean difference in hospital stay was statistically significant at -2.6 (95% CI, -4.48, -0.72, P=0.007) for phenobarbital compared to the benzodiazepine group. We were unable to comment on the heterogeneity in our meta-analysis due to the standard deviation not being reported in one study. There was no statistically significant difference regarding the length of stay in the intensive care unit compared to the control/comparative arm, with a mean difference of -1.17 (95% CI, -1.17, 0.09, P=0.07), with considerable heterogeneity (I=77%, P=0.002). Our meta-analysis also investigated the risk of intubation between the phenobarbital and the control/comparative group. There was statistically significant difference in the incidence of intubation, relative risk (RR) 0.52 (95% CI, 0.25, 1.08, P=0.08), with considerable heterogeneity (I=80%, P=0.0001). Our study concludes that phenobarbital is an effective tool in the management of AWS in an ICU setting. However, various studies have reported contradictory results, and vital information appears to be lacking. Moreover, there is a lack of uniformity in terms of phenobarbital dosing. Drug administration should be adapted according to the severity of the symptoms. Further studies need to be conducted discussing the safety profile and adverse effects of the drug when it comes to the management of alcohol withdrawal syndrome.
PubMed: 36788902
DOI: 10.7759/cureus.33695 -
International Journal of Sports... 2021Deficits in dynamic neuromuscular control have been associated with post-injury sequelae and increased injury risk. The Y-Balance Test Lower Quarter (YBT-LQ) has emerged...
BACKGROUND
Deficits in dynamic neuromuscular control have been associated with post-injury sequelae and increased injury risk. The Y-Balance Test Lower Quarter (YBT-LQ) has emerged as a tool to identify these deficits.
PURPOSE
To review the reliability of the YBT-LQ, determine if performance on the YBT-LQ varies among populations (i.e., sex, sport/activity, and competition level), and to determine the injury risk identification validity of the YBT-LQ based on asymmetry, individual reach direction performance, or composite score.
STUDY DESIGN
Systematic Review.
METHODS
A comprehensive search was performed of 10 online databases from inception to October 30, 2019. Only studies that tested dynamic single leg balance using the YBT-LQ were included. Studies were excluded if the Y-Balance Test kit was not utilized during testing or if there was a major deviation from the Y-Balance test procedure. For methodological quality assessment, the modified Downs and Black scale and the Newcastle-Ottawa Scale were used.
RESULTS
Fifty-seven studies (four in multiple categories) were included with nine studies assessing reliability, 36 assessing population differences, and 16 assessing injury prediction were included. Intra-rater reliability ranged from 0.85-0.91. Sex differences were observed in the posteromedial direction (males: 109.6 [95%CI 107.4-111.8]; females: 102.3 [95%CI 97.2-107.4; p = 0.01]) and posterolateral direction (males: 107.0 [95%CI 105.0-109.1]; females: 102.0 [95%CI 97.8-106.2]). However, no difference was observed between sexes in the anterior reach direction (males: 71.9 [95%CI 69.5-74.5]; females: 70.8 [95%CI 65.7-75.9]; p=0.708). Differences in composite score were noted between soccer (97.6; 95%CI 95.9-99.3) and basketball (92.8; 95%CI 90.4-95.3; p <0.01), and baseball (97.4; 95%CI 94.6-100.2) and basketball (92.8; 95%CI 90.4-95.3; p=0.02). Given the heterogeneity of injury prediction studies, a meta-analysis of these data was not possible. Three of the 13 studies reported a relationship between anterior reach asymmetry reach and injury risk, three of 10 studies for posteromedial and posterolateral reach asymmetry, and one of 13 studies reported relationship with composite reach asymmetry.
CONCLUSIONS
There was moderate to high quality evidence demonstrating that the YBT-LQ is a reliable dynamic neuromuscular control test. Significant differences in sex and sport were observed. If general cut points (i.e., not population specific) are used, the YBT-LQ may not be predictive of injury. Clinical population specific requirements (e.g., age, sex, sport/activity) should be considered when interpreting YBT-LQ performance, particularly when used to identify risk factors for injury.
LEVEL OF EVIDENCE
1b.
PubMed: 34631241
DOI: 10.26603/001c.27634 -
The Journal of Investigative Dermatology Nov 2016Systematic reviews are increasingly utilized in the medical literature to summarize available evidence on a research question. Like other studies, systematic reviews are... (Review)
Review
Systematic reviews are increasingly utilized in the medical literature to summarize available evidence on a research question. Like other studies, systematic reviews are at risk for bias from a number of sources. A systematic review should be based on a formal protocol developed and made publicly available before the conduct of the review; deviations from a protocol with selective presentation of data can result in reporting bias. Evidence selection bias occurs when a systematic review does not identify all available data on a topic. This can arise from publication bias, where data from statistically significant studies are more likely to be published than those that are not statistically significant. Systematic reviews are also susceptible to bias that arises in any of the included primary studies, each of which needs to be critically appraised. Finally, competing interests can lead to bias in favor of a particular intervention. Awareness of these sources of bias is important for authors and consumers of the scientific literature as they conduct and read systematic reviews and incorporate their findings into clinical practice and policy making.
Topics: Dermatology; Disease Management; Humans; Research Design; Selection Bias; Skin Diseases
PubMed: 27772550
DOI: 10.1016/j.jid.2016.08.021 -
Periodontology 2000 Feb 2023Flapless and fully guided implant placement has the potential to maximize efficacy outcomes and at the same time to minimize surgical invasiveness. The aim of the... (Meta-Analysis)
Meta-Analysis Review
Flapless and fully guided implant placement has the potential to maximize efficacy outcomes and at the same time to minimize surgical invasiveness. The aim of the current systematic review was to answer the following PICO question: "In adult human subjects undergoing dental implant placement (P), is minimally invasive flapless computer-aided fully guided (either dynamic or static computer-aided implant placement (sCAIP)) (I) superior to flapped conventional (free-handed implant placement (FHIP) or cast-based/drill partially guided implant placement (dPGIP)) surgery (C), in terms of efficacy, patient morbidity, long-term prognosis, and costs (O)?" Randomized clinical trials (RCTs) fulfilling specific inclusion criteria established to answer the PICO question were included. Two review authors independently searched for eligible studies, screened the titles and abstracts, performed full-text analysis, extracted the data from the published reports, and performed the risk of bias assessment. In cases of disagreement, a third review author took the final decision during ad hoc consensus meetings. The study results were summarized using random effects meta-analyses, which were based (wherever possible) on individual patient data (IPD). A total of 10 manuscripts reporting on five RCTs, involving a total of 124 participants and 449 implants, and comparing flapless sCAIP with flapped FHIP/cast-based partially guided implant placement (cPGIP), were included. There was no RCT analyzing flapless dynamic computer-aided implant placement (dCAIP) or flapped dPGIP. Intergroup meta-analyses indicated less depth deviation (difference in means (MD) = -0.28 mm; 95% confidence interval (CI): -0.59 to 0.03; moderate certainty), angular deviation (MD = -3.88 degrees; 95% CI: -7.00 to -0.77; high certainty), coronal (MD = -0.6 mm; 95% CI: -1.21 to 0.01; low certainty) and apical (MD = -0.75 mm; 95% CI: -1.43 to -0.07; moderate certainty) three-dimensional bodily deviations, postoperative pain (MD = -17.09 mm on the visual analogue scale (VAS); 95% CI: -33.38 to -0.80; low certainty), postoperative swelling (MD = -6.59 mm on the VAS; 95% CI: -19.03 to 5.85; very low certainty), intraoperative discomfort (MD = -9.36 mm on the VAS; 95% CI: -17.10 to -1.61) and surgery duration (MD = -24.28 minutes; 95% CI: -28.62 to -19.95) in flapless sCAIP than in flapped FHIP/cPGIP. Despite being more accurate than flapped FHIP/cPGIP, flapless sCAIP still resulted in deviations with respect to the planned position (intragroup meta-analytic means: 0.76 mm in depth, 2.57 degrees in angular, 1.43 mm in coronal, and 1.68 in apical three-dimensional bodily position). Moreover, flapless sCAIP presented a 12% group-specific intraoperative complication rate, resulting in an inability to place the implant with this protocol in 7% of cases. Evidence regarding more clinically relevant outcomes of efficacy (implant survival and success, prosthetically and biologically correct positioning), long-term prognosis, and costs, is currently scarce. When the objective is to guarantee minimal invasiveness at implant placement, clinicians could consider the use of flapless sCAIP. A proper case selection and consideration of a safety margin are, however, suggested.
Topics: Adult; Humans; Dental Implants; Dental Implantation, Endosseous; Surgery, Computer-Assisted; Surgical Flaps
PubMed: 35906928
DOI: 10.1111/prd.12440 -
Journal of Prosthodontic Research Jan 2022To review the current clinical studies regarding the accuracy of implant computer-guided surgery in partially edentulous patients and investigate potential influencing... (Meta-Analysis)
Meta-Analysis
PURPOSE
To review the current clinical studies regarding the accuracy of implant computer-guided surgery in partially edentulous patients and investigate potential influencing factors.
STUDY SELECTION
Electronic searches on the PubMed and Cochrane Central Register of Controlled Trials databases, and subsequent manual searches were performed. Two reviewers selected the studies following our inclusion and exclusion criteria. Qualitative review and meta-analysis of the implant placement accuracy were performed to analyze potential influencing factors. Angular deviation, coronal deviation, apical deviation, and depth deviation were evaluated as the accuracy outcomes.
RESULTS
Eighteen studies were included in this systematic review, including six randomized controlled trials, nine prospective studies, and three retrospective clinical studies. A total of 1317 implants placed in 642 partially edentulous patients were reviewed. Eight studies were evaluated using meta-analysis. Fully guided surgery showed statistically higher accuracy in angular (P <0.001), coronal (P <0.001), and apical deviation (P <0.05) compared with pilot-drill guided surgery. A statistically significant difference (P <0.001) was also observed in coronal deviation between the bounded edentulous (BES) and distal extension spaces (DES). A significantly lower angular deviation (P <0.001) was found in implants placed using computer-aided design/computer-aided manufacturing (CAD/CAM) compared to the conventional surgical guides.
CONCLUSION
The edentulous space type, surgical guide manufacturing procedure, and guided surgery protocol can influence the accuracy of computer-guided surgery in partially edentulous patients. Higher accuracy was found when the implants were placed in BES, with CAD/CAM manufactured surgical guides, using a fully guided surgery protocol.
Topics: Computer-Aided Design; Computers; Cone-Beam Computed Tomography; Dental Implantation, Endosseous; Dental Implants; Humans; Prospective Studies; Retrospective Studies; Surgery, Computer-Assisted
PubMed: 33504723
DOI: 10.2186/jpr.JPR_D_20_00184 -
The Cochrane Database of Systematic... Feb 2022Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria since it was first introduced in Malawi in 1993 (Filler 2006). Due to increasing resistance to SP, in 2000 the WHO recommended that one of several artemisinin-based combination therapies (ACTs) be used instead of SP for the treatment of uncomplicated malaria caused by Plasmodium falciparum (Global Partnership to Roll Back Malaria 2001). However, despite these recommendations, SP continues to be advised for intermittent preventive treatment in pregnancy (IPTp) and intermittent preventive treatment in infants (IPTi), whether the person has malaria or not (WHO 2013). Description of the intervention Folate (vitamin B9) includes both naturally occurring folates and folic acid, the fully oxidized monoglutamic form of the vitamin, used in dietary supplements and fortified food. Folate deficiency (e.g. red blood cell (RBC) folate concentrations of less than 305 nanomoles per litre (nmol/L); serum or plasma concentrations of less than 7 nmol/L) is common in many parts of the world and often presents as megaloblastic anaemia, resulting from inadequate intake, increased requirements, reduced absorption, or abnormal metabolism of folate (Bailey 2015; WHO 2015a). Pregnant women have greater folate requirements; inadequate folate intake (evidenced by RBC folate concentrations of less than 400 nanograms per millilitre (ng/mL), or 906 nmol/L) prior to and during the first month of pregnancy increases the risk of neural tube defects, preterm delivery, low birthweight, and fetal growth restriction (Bourassa 2019). The WHO recommends that all women who are trying to conceive consume 400 micrograms (µg) of folic acid daily from the time they begin trying to conceive through to 12 weeks of gestation (WHO 2017). In 2015, the WHO added the dosage of 0.4 mg of folic acid to the essential drug list (WHO 2015c). Alongside daily oral iron (30 mg to 60 mg elemental iron), folic acid supplementation is recommended for pregnant women to prevent neural tube defects, maternal anaemia, puerperal sepsis, low birthweight, and preterm birth in settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin (Hb) concentration of less than 110 g/L). How the intervention might work Potential interactions between folate status and malaria infection The malaria parasite requires folate for survival and growth; this has led to the hypothesis that folate status may influence malaria risk and severity. In rhesus monkeys, folate deficiency has been found to be protective against Plasmodium cynomolgi malaria infection, compared to folate-replete animals (Metz 2007). Alternatively, malaria may induce or exacerbate folate deficiency due to increased folate utilization from haemolysis and fever. Further, folate status measured via RBC folate is not an appropriate biomarker of folate status in malaria-infected individuals since RBC folate values in these individuals are indicative of both the person's stores and the parasite's folate synthesis. A study in Nigeria found that children with malaria infection had significantly higher RBC folate concentrations compared to children without malaria infection, but plasma folate levels were similar (Bradley-Moore 1985). Why it is important to do this review The malaria parasite needs folate for survival and growth in humans. For individuals, adequate folate levels are critical for health and well-being, and for the prevention of anaemia and neural tube defects. Many countries rely on folic acid supplementation to ensure adequate folate status in at-risk populations. Different formulations for folic acid supplements are available in many international settings, with dosages ranging from 400 µg to 5 mg. Evaluating folic acid dosage levels used in supplementation efforts may increase public health understanding of its potential impacts on malaria risk and severity and on treatment failures. Examining folic acid interactions with antifolate antimalarial medications and with malaria disease progression may help countries in malaria-endemic areas determine what are the most appropriate lower dose folic acid formulations for at-risk populations. The WHO has highlighted the limited evidence available and has indicated the need for further research on biomarkers of folate status, particularly interactions between RBC folate concentrations and tuberculosis, human immunodeficiency virus (HIV), and antifolate antimalarial drugs (WHO 2015b). An earlier Cochrane Review assessed the effects and safety of iron supplementation, with or without folic acid, in children living in hyperendemic or holoendemic malaria areas; it demonstrated that iron supplementation did not increase the risk of malaria, as indicated by fever and the presence of parasites in the blood (Neuberger 2016). Further, this review stated that folic acid may interfere with the efficacy of SP; however, the efficacy and safety of folic acid supplementation on these outcomes has not been established. This review will provide evidence on the effectiveness of daily folic acid supplementation in healthy and malaria-infected individuals living in malaria-endemic areas. Additionally, it will contribute to achieving both the WHO Global Technical Strategy for Malaria 2016-2030 (WHO 2015d), and United Nations Sustainable Development Goal 3 (to ensure healthy lives and to promote well-being for all of all ages) (United Nations 2021), and evaluating whether the potential effects of folic acid supplementation, at different doses (e.g. 0.4 mg, 1 mg, 5 mg daily), interferes with the effect of drugs used for prevention or treatment of malaria.
OBJECTIVES
To examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?
METHODS
Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (including but not limited to sulfadoxine/pyrimethamine (SP), pyrimethamine-dapsone, pyrimethamine, chloroquine and proguanil, cotrimoxazole) for the prevention or treatment of malaria (studies will be included if more than 70% of the participants live in malaria-endemic regions) Studies assessing participants with or without anaemia and with or without malaria parasitaemia at baseline will be included Exclusion criteria Individuals not taking antifolate antimalarial medications for prevention or treatment of malaria Individuals living in non-malaria endemic areas Types of interventions Inclusion criteria Folic acid supplementation Form: in tablet, capsule, dispersible tablet at any dose, during administration, or periodically Timing: during, before, or after (within a period of four to six weeks) administration of antifolate antimalarials Iron-folic acid supplementation Folic acid supplementation in combination with co-interventions that are identical between the intervention and control groups. Co-interventions include: anthelminthic treatment; multivitamin or multiple micronutrient supplementation; 5-methyltetrahydrofolate supplementation. Exclusion criteria Folate through folate-fortified water Folic acid administered through large-scale fortification of rice, wheat, or maize Comparators Placebo No treatment No folic acid/different doses of folic acid Iron Types of outcome measures Primary outcomes Uncomplicated malaria (defined as a history of fever with parasitological confirmation; acceptable parasitological confirmation will include rapid diagnostic tests (RDTs), malaria smears, or nucleic acid detection (i.e. polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), etc.)) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Severe malaria (defined as any case with cerebral malaria or acute P. falciparum malaria, with signs of severity or evidence of vital organ dysfunction, or both) (WHO 2010). This outcome is relevant for patients without malaria, given antifolate antimalarials for malaria prophylaxis. Parasite clearance (any Plasmodium species), defined as the time it takes for a patient who tests positive at enrolment and is treated to become smear-negative or PCR negative. This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Treatment failure (defined as the inability to clear malaria parasitaemia or prevent recrudescence after administration of antimalarial medicine, regardless of whether clinical symptoms are resolved) (WHO 2019). This outcome is relevant for patients with malaria, treated with antifolate antimalarials. Secondary outcomes Duration of parasitaemia Parasite density Haemoglobin (Hb) concentrations (g/L) Anaemia: severe anaemia (defined as Hb less than 70 g/L in pregnant women and children aged six to 59 months; and Hb less than 80 g/L in other populations); moderate anaemia (defined as Hb less than 100 g/L in pregnant women and children aged six to 59 months; and less than 110 g/L in others) Death from any cause Among pregnant women: stillbirth (at less than 28 weeks gestation); low birthweight (less than 2500 g); active placental malaria (defined as Plasmodium detected in placental blood by smear or PCR, or by Plasmodium detected on impression smear or placental histology). Search methods for identification of studies A search will be conducted to identify completed and ongoing studies, without date or language restrictions. Electronic searches A search strategy will be designed to include the appropriate subject headings and text word terms related to each intervention of interest and study design of interest (see Appendix 1). Searches will be broken down by these two criteria (intervention of interest and study design of interest) to allow for ease of prioritization, if necessary. The study design filters recommended by the Scottish Intercollegiate Guidelines Network (SIGN), and those designed by Cochrane for identifying clinical trials for MEDLINE and Embase, will be used (SIGN 2020). There will be no date or language restrictions. Non-English articles identified for inclusion will be translated into English. If translations are not possible, advice will be requested from the Cochrane Infectious Diseases Group and the record will be stored in the "Awaiting assessment" section of the review until a translation is available. The following electronic databases will be searched for primary studies. Cochrane Central Register of Controlled Trials. Cumulative Index to Nursing and Allied Health Literature (CINAHL). Embase. MEDLINE. Scopus. Web of Science (both the Social Science Citation Index and the Science Citation Index). We will conduct manual searches of ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the United Nations Children's Fund (UNICEF) Evaluation and Research Database (ERD), in order to identify relevant ongoing or planned trials, abstracts, and full-text reports of evaluations, studies, and surveys related to programmes on folic acid supplementation in malaria-endemic areas. Additionally, manual searches of grey literature to identify RCTs that have not yet been published but are potentially eligible for inclusion will be conducted in the following sources. Global Index Medicus (GIM). African Index Medicus (AIM). Index Medicus for the Eastern Mediterranean Region (IMEMR). Latin American & Caribbean Health Sciences Literature (LILACS). Pan American Health Organization (PAHO). Western Pacific Region Index Medicus (WPRO). Index Medicus for the South-East Asian Region (IMSEAR). The Spanish Bibliographic Index in Health Sciences (IBECS) (ibecs.isciii.es/). Indian Journal of Medical Research (IJMR) (journals.lww.com/ijmr/pages/default.aspx). Native Health Database (nativehealthdatabase.net/). Scielo (www.scielo.br/). Searching other resources Handsearches of the five journals with the highest number of included studies in the last 12 months will be conducted to capture any relevant articles that may not have been indexed in the databases at the time of the search. We will contact the authors of included studies and will check reference lists of included papers for the identification of additional records. For assistance in identifying ongoing or unpublished studies, we will contact the Division of Nutrition, Physical Activity, and Obesity (DNPAO) and the Division of Parasitic Diseases and Malaria (DPDM) of the CDC, the United Nations World Food Programme (WFP), Nutrition International (NI), Global Alliance for Improved Nutrition (GAIN), and Hellen Keller International (HKI). Data collection and analysis Selection of studies Two review authors will independently screen the titles and abstracts of articles retrieved by each search to assess eligibility, as determined by the inclusion and exclusion criteria. Studies deemed eligible for inclusion by both review authors in the abstract screening phase will advance to the full-text screening phase, and full-text copies of all eligible papers will be retrieved. If full articles cannot be obtained, we will attempt to contact the authors to obtain further details of the studies. If such information is not obtained, we will classify the study as "awaiting assessment" until further information is published or made available to us. The same two review authors will independently assess the eligibility of full-text articles for inclusion in the systematic review. If any discrepancies occur between the studies selected by the two review authors, a third review author will provide arbitration. Each trial will be scrutinized to identify multiple publications from the same data set, and the justification for excluded trials will be documented. A PRISMA flow diagram of the study selection process will be presented to provide information on the number of records identified in the literature searches, the number of studies included and excluded, and the reasons for exclusion (Moher 2009). The list of excluded studies, along with their reasons for exclusion at the full-text screening phase, will also be created. Data extraction and management Two review authors will independently extract data for the final list of included studies using a standardized data specification form. Discrepancies observed between the data extracted by the two authors will be resolved by involving a third review author and reaching a consensus. Information will be extracted on study design components, baseline participant characteristics, intervention characteristics, and outcomes. For individually randomized trials, we will record the number of participants experiencing the event and the number analyzed in each treatment group or the effect estimate reported (e.g. risk ratio (RR)) for dichotomous outcome measures. For count data, we will record the number of events and the number of person-months of follow-up in each group. If the number of person-months is not reported, the product of the duration of follow-up and the number of children evaluated will be used to estimate this figure. We will calculate the rate ratio and standard error (SE) for each study. Zero events will be replaced by 0.5. We will extract both adjusted and unadjusted covariate incidence rate ratios if they are reported in the original studies. For continuous data, we will extract means (arithmetic or geometric) and a measure of variance (standard deviation (SD), SE, or confidence interval (CI)), percentage or mean change from baseline, and the numbers analyzed in each group. SDs will be computed from SEs or 95% CIs, assuming a normal distribution of the values. Haemoglobin values in g/dL will be calculated by multiplying haematocrit or packed cell volume values by 0.34, and studies reporting haemoglobin values in g/dL will be converted to g/L. In cluster-randomized trials, we will record the unit of randomization (e.g. household, compound, sector, or village), the number of clusters in the trial, and the average cluster size. The statistical methods used to analyze the trials will be documented, along with details describing whether these methods adjusted for clustering or other covariates. We plan to extract estimates of the intra-cluster correlation coefficient (ICC) for each outcome. Where results are adjusted for clustering, we will extract the treatment effect estimate and the SD or CI. If the results are not adjusted for clustering, we will extract the data reported. Assessment of risk of bias in included studies Two review authors (KSC, LFY) will independently assess the risk of bias for each included trial using the Cochrane 'Risk of bias 2' tool (RoB 2) for randomized studies (Sterne 2019). Judgements about the risk of bias of included studies will be made according to the recommendations outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). Disagreements will be resolved by discussion, or by involving a third review author. The interest of our review will be to assess the effect of assignment to the interventions at baseline. We will evaluate each primary outcome using the RoB2 tool. The five domains of the Cochrane RoB2 tool include the following. Bias arising from the randomization process. Bias due to deviations from intended interventions. Bias due to missing outcome data. Bias in measurement of the outcome. Bias in selection of the reported result. Each domain of the RoB2 tool comprises the following. A series of 'signalling' questions. A judgement about the risk of bias for the domain, facilitated by an algorithm that maps responses to the signalling questions to a proposed judgement. Free-text boxes to justify responses to the signalling questions and 'Risk of bias' judgements. An option to predict (and explain) the likely direction of bias. Responses to signalling questions elicit information relevant to an assessment of the risk of bias. These response options are as follows. Yes (may indicate either low or high risk of bias, depending on the most natural way to ask the question). Probably yes. Probably no. No. No information (may indicate no evidence of that problem or an absence of information leading to concerns about there being a problem). Based on the answer to the signalling question, a 'Risk of bias' judgement is assigned to each domain. These judgements include one of the following. High risk of bias Low risk of bias Some concerns To generate the risk of bias judgement for each domain in the randomized studies, we will use the Excel template, available at www.riskofbias.info/welcome/rob-2-0-tool/current-version-of-rob-2. This file will be stored on a scientific data website, available to readers. Risk of bias in cluster randomized controlled trials For the cluster randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 1b (bias arising from the timing of identification or recruitment of participants) and its related signalling questions. To generate the risk of bias judgement for each domain in the cluster RCTs, we will use the Excel template available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-cluster-randomized-trials. This file will be stored on a scientific data website, available to readers. Risk of bias in cross-over randomized controlled trials For cross-over randomized trials, we will be using the RoB2 tool to analyze the five standard domains listed above along with Domain 2 (bias due to deviations from intended interventions), and Domain 3 (bias due to missing outcome data), and their respective signalling questions. To generate the risk of bias judgement for each domain in the cross-over RCTs, we will use the Excel template, available at https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/rob-2-for-crossover-trials, for each risk of bias judgement of cross-over randomized studies. This file will be stored on a scientific data website, available to readers. Overall risk of bias The overall 'Risk of bias' judgement for each specific trial being assessed will be based on each domain-level judgement. The overall judgements include the following. Low risk of bias (the trial is judged to be at low risk of bias for all domains). Some concerns (the trial is judged to raise some concerns in at least one domain but is not judged to be at high risk of bias for any domain). High risk of bias (the trial is judged to be at high risk of bias in at least one domain, or is judged to have some concerns for multiple domains in a way that substantially lowers confidence in the result). The 'risk of bias' assessments will inform our GRADE evaluations of the certainty of evidence for our primary outcomes presented in the 'Summary of findings' tables and will also be used to inform the sensitivity analyses; (see Sensitivity analysis). If there is insufficient information in study reports to enable an assessment of the risk of bias, studies will be classified as "awaiting assessment" until further information is published or made available to us. Measures of treatment effect Dichotomous data For dichotomous data, we will present proportions and, for two-group comparisons, results as average RR or odds ratio (OR) with 95% CIs. Ordered categorical data Continuous data We will report results for continuous outcomes as the mean difference (MD) with 95% CIs, if outcomes are measured in the same way between trials. Where some studies have reported endpoint data and others have reported change-from-baseline data (with errors), we will combine these in the meta-analysis, if the outcomes were reported using the same scale. We will use the standardized mean difference (SMD), with 95% CIs, to combine trials that measured the same outcome but used different methods. If we do not find three or more studies for a pooled analysis, we will summarize the results in a narrative form. Unit of analysis issues Cluster-randomized trials We plan to combine results from both cluster-randomized and individually randomized studies, providing there is little heterogeneity between the studies. If the authors of cluster-randomized trials conducted their analyses at a different level from that of allocation, and they have not appropriately accounted for the cluster design in their analyses, we will calculate the trials' effective sample sizes to account for the effect of clustering in data. When one or more cluster-RCT reports RRs adjusted for clustering, we will compute cluster-adjusted SEs for the other trials. When none of the cluster-RCTs provide cluster-adjusted RRs, we will adjust the sample size for clustering. We will divide, by the estimated design effects (DE), the number of events and number evaluated for dichotomous outcomes and the number evaluated for continuous outcomes, where DE = 1 + ((average cluster size 1) * ICC). The derivation of the estimated ICCs and DEs will be reported. We will utilize the intra-cluster correlation coefficient (ICC), derived from the trial (if available), or from another source (e.g., using the ICCs derived from other, similar trials) and then calculate the design effect with the formula provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021). If this approach is used, we will report it and undertake sensitivity analysis to investigate the effect of variations in ICC. Studies with more than two treatment groups If we identify studies with more than two intervention groups (multi-arm studies), where possible we will combine groups to create a single pair-wise comparison or use the methods set out in the Cochrane Handbook to avoid double counting study participants (Higgins 2021). For the subgroup analyses, when the control group was shared by two or more study arms, we will divide the control group (events and total population) over the number of relevant subgroups to avoid double counting the participants. Trials with several study arms can be included more than once for different comparisons. Cross-over trials From cross-over trials, we will consider the first period of measurement only and will analyze the results together with parallel-group studies. Multiple outcome events In several outcomes, a participant might experience more than one outcome event during the trial period. For all outcomes, we will extract the number of participants with at least one event. Dealing with missing data We will contact the trial authors if the available data are unclear, missing, or reported in a format that is different from the format needed. We aim to perform a 'per protocol' or 'as observed' analysis; otherwise, we will perform a complete case analysis. This means that for treatment failure, we will base the analyses on the participants who received treatment and the number of participants for which there was an inability to clear malarial parasitaemia or prevent recrudescence after administration of an antimalarial medicine reported in the studies. Assessment of heterogeneity Heterogeneity in the results of the trials will be assessed by visually examining the forest plot to detect non-overlapping CIs, using the Chi2 test of heterogeneity (where a P value of less than 0.1 indicates statistical significance) and the I2 statistic of inconsistency (with a value of greater than 50% denoting moderate levels of heterogeneity). When statistical heterogeneity is present, we will investigate the reasons for it, using subgroup analysis. Assessment of reporting biases We will construct a funnel plot to assess the effect of small studies for the main outcome (when including more than 10 trials). Data synthesis The primary analysis will include all eligible studies that provide data regardless of the overall risk of bias as assessed by the RoB2 tool. Analyses will be conducted using Review Manager 5.4 (Review Manager 2020). Cluster-RCTs will be included in the main analysis after adjustment for clustering (see the previous section on cluster-RCTs). The meta-analysis will be performed using the Mantel-Haenszel random-effects model or the generic inverse variance method (when adjustment for clustering is performed by adjusting SEs), as appropriate. Subgroup analysis and investigation of heterogeneity The overall risk of bias will not be used as the basis in conducting our subgroup analyses. However, where data are available, we plan to conduct the following subgroup analyses, independent of heterogeneity. Dose of folic acid supplementation: higher doses (4 mg or more, daily) versus lower doses (less than 4 mg, daily). Moderate-severe anaemia at baseline (mean haemoglobin of participants in a trial at baseline below 100 g/L for pregnant women and children aged six to 59 months, and below 110 g/L for other populations) versus normal at baseline (mean haemoglobin above 100 g/L for pregnant women and children aged six to 59 months, and above 110 g/L for other populations). Antimalarial drug resistance to parasite: known resistance versus no resistance versus unknown/mixed/unreported parasite resistance. Folate status at baseline: Deficient (e.g. RBC folate concentration of less than 305 nmol/L, or serum folate concentration of less than 7nmol/L) and Insufficient (e.g. RBC folate concentration from 305 to less than 906 nmol/L, or serum folate concentration from 7 to less than 25 nmol/L) versus Sufficient (e.g. RBC folate concentration above 906 nmol/L, or serum folate concentration above 25 nmol/L). Presence of anaemia at baseline: yes versus no. Mandatory fortification status: yes, versus no (voluntary or none). We will only use the primary outcomes in any subgroup analyses, and we will limit subgroup analyses to those outcomes for which three or more trials contributed data. Comparisons between subgroups will be performed using Review Manager 5.4 (Review Manager 2020). Sensitivity analysis We will perform a sensitivity analysis, using the risk of bias as a variable to explore the robustness of the findings in our primary outcomes. We will verify the behaviour of our estimators by adding and removing studies with a high risk of bias overall from the analysis. That is, studies with a low risk of bias versus studies with a high risk of bias. Summary of findings and assessment of the certainty of the evidence For the assessment across studies, we will use the GRADE approach, as outlined in (Schünemann 2021). We will use the five GRADE considerations (study limitations based on RoB2 judgements, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence as it relates to the studies which contribute data to the meta-analyses for the primary outcomes. The GRADEpro Guideline Development Tool (GRADEpro) will be used to import data from Review Manager 5.4 (Review Manager 2020) to create 'Summary of Findings' tables. The primary outcomes for the main comparison will be listed with estimates of relative effects, along with the number of participants and studies contributing data for those outcomes. These tables will provide outcome-specific information concerning the overall certainty of evidence from studies included in the comparison, the magnitude of the effect of the interventions examined, and the sum of available data on the outcomes we considered. We will include only primary outcomes in the summary of findings tables. For each individual outcome, two review authors (KSC, LFY) will independently assess the certainty of the evidence using the GRADE approach (Balshem 2011). For assessments of the overall certainty of evidence for each outcome that includes pooled data from included trials, we will downgrade the evidence from 'high certainty' by one level for serious (or by two for very serious) study limitations (risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias).
Topics: Child; Infant; Pregnancy; Infant, Newborn; Female; Humans; Child, Preschool; Antimalarials; Sulfadoxine; Pyrimethamine; Folic Acid Antagonists; Birth Weight; Parasitemia; Vitamins; Folic Acid; Anemia; Neural Tube Defects; Dietary Supplements; Iron; Recurrence
PubMed: 36321557
DOI: 10.1002/14651858.CD014217 -
EClinicalMedicine Mar 2023Knowing the prevalence of multimorbidity among adults across continents is a crucial piece of information for achieving Sustainable Development Goal 3.4, which calls for...
BACKGROUND
Knowing the prevalence of multimorbidity among adults across continents is a crucial piece of information for achieving Sustainable Development Goal 3.4, which calls for reducing premature death due to non-communicable diseases. A high prevalence of multimorbidity indicates high mortality and increased healthcare utilization. We aimed to understand the prevalence of multimorbidity across WHO geographic regions among adults.
METHODS
We performed a systematic review and meta-analysis of surveys designed to estimate the prevalence of multimorbidity among adults in community settings. We searched PubMed, ScienceDirect, Embase and Google Scholar databases for studies published between January 1, 2000, and December 31, 2021. The random-effects model estimated the pooled proportion of multimorbidity in adults. Heterogeneity was quantified using I statistics. We performed subgroup analyses and sensitivity analyses based on continents, age, gender, multimorbidity definition, study periods and sample size. The study protocol was registered with PROSPERO (CRD42020150945).
FINDINGS
We analyzed data from 126 peer-reviewed studies that included nearly 15.4 million people (32.1% were male) with a weighted mean age of 56.94 years (standard deviation of 10.84 years) from 54 countries around the world. The overall global prevalence of multimorbidity was 37.2% (95% CI = 34.9-39.4%). South America (45.7%, 95% CI = 39.0-52.5) had the highest prevalence of multimorbidity, followed by North America (43.1%, 95% CI = 32.3-53.8%), Europe (39.2%, 95% CI = 33.2-45.2%), and Asia (35%, 95% CI = 31.4-38.5%). The subgroup study highlights that multimorbidity is more prevalent in females (39.4%, 95% CI = 36.4-42.4%) than males (32.8%, 95% CI = 30.0-35.6%). More than half of the adult population worldwide above 60 years of age had multimorbid conditions (51.0%, 95% CI = 44.1-58.0%). Multimorbidity has become increasingly prevalent in the last two decades, while the prevalence appears to have stayed stable in the recent decade among adults globally.
INTERPRETATION
The multimorbidity patterns by geographic regions, time, age, and gender suggest noticeable demographic and regional differences in the burden of multimorbidity. According to insights about prevalence among adults, priority is required for effective and integrative interventions for older adults from South America, Europe, and North America. A high prevalence of multimorbidity among adults from South America suggests immediate interventions are needed to reduce the burden of morbidity. Furthermore, the high prevalence trend in the last two decades indicates that the global burden of multimorbidity continues at the same pace. The low prevalence in Africa suggests that there may be many undiagnosed chronic illness patients in Africa.
FUNDING
None.
PubMed: 36864977
DOI: 10.1016/j.eclinm.2023.101860 -
BMC Musculoskeletal Disorders Jul 2021The purpose of this systematic review and meta-analysis is to compare the conservative and accelerated rehabilitation protocols in patients who underwent arthroscopic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this systematic review and meta-analysis is to compare the conservative and accelerated rehabilitation protocols in patients who underwent arthroscopic rotator cuff repair in terms of clinical outcomes and range of motions at 3, 6, 12, and 24-month follow-up.
METHODS
According to PRISMA guidelines, a systematic review of the literature was performed. For each included article, the following data has been extracted: authors, year, study design, level of evidence, demographic characteristics, follow-up, clinical outcomes, range of motions, and retear events. A meta-analysis was performed to compare accelerated versus conservative rehabilitation protocols after arthroscopic rotator cuff repair. The retear rate, postoperative Constant-Murley score and range of motions at 3, 6, 12, and 24 months of follow-up were the outcomes measured.
RESULTS
The search strategy yielded 16 level I-II clinical studies. A total of 1424 patients, with 732 patients and 692 in the accelerated and conservative group, were included. The average age (mean ± standard deviation) was 56.1 ± 8.7 and 56.6 ± 9 in the accelerated and conservative group. The mean follow-up was 12.5 months, ranging from 2 to 24 months. The meta-analysis showed no statistically significant differences in terms of retear rate between the groups (P = 0.29). The superiority of the accelerated group was demonstrated in terms of external rotation (P < 0.05) at 3-month follow-up; in terms of forward elevation, external rotation, abduction (P < 0.05), but not in terms of Constant-Murley score at 6-month follow-up; in terms of forward elevation (P < 0.05) at 12-month follow-up. No significant differences between the two group were highlighted at 24-month follow-up.
CONCLUSIONS
No statistically significant differences in the retear rate among the accelerated and conservative group have been demonstrated. On the other hand, statistically and clinically significant differences were found in terms of external rotation at 3 and 6 months of follow-up in favour of the accelerated group. However, no differences between the two groups were detected at 24 months follow-up.
Topics: Arthroscopy; Humans; Range of Motion, Articular; Rotator Cuff; Rotator Cuff Injuries; Treatment Outcome
PubMed: 34303366
DOI: 10.1186/s12891-021-04397-0 -
Journal of Lasers in Medical Sciences 2020High-intensity laser therapy (HILT) has been used more recently in the therapeutic protocols of pain managements. Adding therapeutic interventions to laser therapy is... (Review)
Review
High-intensity laser therapy (HILT) has been used more recently in the therapeutic protocols of pain managements. Adding therapeutic interventions to laser therapy is usual in clinical practice. This study aimed to evaluate the efficacy of HILT and beneficial effects of adding cointerventions to HILT in musculoskeletal pain management. The following databases were searched up to August 2018: Medline, PubMed, EMBASE, Cochrane, Google Scholar, Springer and ISI. The keywords of pain, HILT, high power laser therapy, laser therapy, photobiomodulation, physical therapy and rehabilitation were searched. The quality of the articles was assessed using the PEDro scale. The primary measure was pain severity expected to be reported in all studies. Effect size was calculated as standardized mean differences divided by the standard deviation of either the treatment or other group. Initially 52 potential studies were found. Eighteen of these studies were excluded based on title and abstract. The full text of 34 remaining articles was screened and 15 of the studies were excluded. All included studies had high quality (PEDro ≥7). Approximately, 94% of included articles (n=18) revealed positive effects of HILT on pain. The effect sizes for HILT and placebo/comparator groups were 0.9-9.11 and 0.21-11.22 respectively. Also, the differences of effect size between two groups were between 0.03 to 5.85. It is early to determine that HILT may be an effective non-invasive agent in the management of musculoskeletal pain, as few studies have shown its clinical efficacy. Adding related co-interventions to HILT may enhance the beneficial effects of laser therapy. The variability of the study methods and outcomes suggests that further long-term follow-up, randomized controlled clinical trials with appropriate methodological design are needed regarding the effectiveness of HILT on pain.
PubMed: 32099632
DOI: 10.15171/jlms.2020.14 -
BMC Medicine Aug 2022During the COVID-19 pandemic, there have been concerns regarding potential bias in pulse oximetry measurements for people with high levels of skin pigmentation. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
During the COVID-19 pandemic, there have been concerns regarding potential bias in pulse oximetry measurements for people with high levels of skin pigmentation. We systematically reviewed the effects of skin pigmentation on the accuracy of oxygen saturation measurement by pulse oximetry (SpO) compared with the gold standard SaO measured by CO-oximetry.
METHODS
We searched Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform (up to December 2021) for studies with SpO-SaO comparisons and measuring the impact of skin pigmentation or ethnicity on pulse oximetry accuracy. We performed meta-analyses for mean bias (the primary outcome in this review) and its standard deviations (SDs) across studies included for each subgroup of skin pigmentation and ethnicity and used these pooled mean biases and SDs to calculate accuracy root-mean-square (A) and 95% limits of agreement. The review was registered with the Open Science Framework ( https://osf.io/gm7ty ).
RESULTS
We included 32 studies (6505 participants): 15 measured skin pigmentation and 22 referred to ethnicity. Compared with standard SaO measurement, pulse oximetry probably overestimates oxygen saturation in people with the high level of skin pigmentation (pooled mean bias 1.11%; 95% confidence interval 0.29 to 1.93%) and people described as Black/African American (1.52%; 0.95 to 2.09%) (moderate- and low-certainty evidence). The bias of pulse oximetry measurements for people with other levels of skin pigmentation or those from other ethnic groups is either more uncertain or suggests no overestimation. Whilst the extent of mean bias is small or negligible for all subgroups evaluated, the associated imprecision is unacceptably large (pooled SDs > 1%). When the extent of measurement bias and precision is considered jointly, pulse oximetry measurements for all the subgroups appear acceptably accurate (with A < 4%).
CONCLUSIONS
Pulse oximetry may overestimate oxygen saturation in people with high levels of skin pigmentation and people whose ethnicity is reported as Black/African American, compared with SaO. The extent of overestimation may be small in hospital settings but unknown in community settings. REVIEW PROTOCOL REGISTRATION: https://osf.io/gm7ty.
Topics: COVID-19; Humans; Oximetry; Oxygen; Oxygen Saturation; Pandemics; Skin Pigmentation
PubMed: 35971142
DOI: 10.1186/s12916-022-02452-8