Protocol Registration Research Articles

Using primary care data to understand opioid prescribing, policy impacts and clinical outcomes: A protocol for the OPPICO study

IntroductionPrescription opioid use in Australia has increased over the last 3 decades. The majority of opioids are prescribed and dispensed in primary care, however, there are few studies that are specific to opioid prescribing in this setting. Evidence about the impact of key government policy strategies to optimize opioid prescribing in primary care is limited. The aim of this study is to examine the impact of recent policy changes and clinical guidelines on opioid prescribing in primary care. Methods and analysisLongitudinal analysis of people prescribed opioid analgesics using Population Level Analysis and Reporting (POLAR) data. POLAR is a primary care dataset comprising 464 primary health care practices in Victoria, Australia. People prescribed opioid analgesics between 2015 and 2020 will be included. The impact of opioid policies and guideline recommendations will be evaluated using interrupted time series models. Group- based trajectory modelling and multivariate regression will be used to identify patterns of opioid cessation and the provision of corresponding non-opioid interventions. Ethics and disseminationThe study has received Monash University Human Research Ethics Committee approval (ID 24139). Permission to access, collate and use POLAR data is granted from Outcome Health as the data custodians. The results of this study will be disseminated through publication in international journals, presented at national and international scientific conferences, and disseminated to consumers, policy makers, primary care providers and primary health networks. Protocol registration detailsEU PAS Register (EUPAS43218)

An overview of the characteristics and methodological standards across systematic reviews with Meta-analysis of efficacy/effectiveness of influenza antiviral drugs

Background Influenza antiviral drugs remain controversial and it is not clear if conclusions on their efficacy/effectiveness are based on high quality systematic reviews (SRs). We systematically identified, critically appraised, and summarized the characteristics and adherence to methodological standards in SRs with meta-analysis of efficacy/effectiveness of influenza antiviral drugs for prevention and/or treatment of influenza. Methods We searched MEDLINE, Embase, Scopus, CINAHL, Global Health, and CDSR for English-language SR publications up to July 2020. We summarized the characteristics, adherence to methodological standards and SR quality (AMSTAR 2). Results From a total 3,898 citations after removal of duplicates from all identified citations, we included 24 SRs. Seventy-five percent (n = 18) were of a critically low quality, 8% (n = 2) of a low quality, 17% (n = 4) of a moderate quality, and none were of a high quality. Seventeen percent (n = 4) were industry-funded, 4% (n = 1) coauthored by industry employee(s), and 33% (n = 8) commissioned by an organization or authority. Only 33% percent (n = 8) reported protocol registration, 4% (n = 1) reported collaboration with a knowledge synthesis librarian/information specialist, and 17% (n = 4) utilized a systematic review reporting checklist. Conclusions The evidence suggests that SRs of efficacy/effectiveness of influenza antiviral drugs are mostly of critically low quality and do not follow current best SR practices. These findings are significant in view of the important role of SRs in decision-making and the controversies that surround the use of the influenza antiviral drugs. However, the findings should not be interpreted to mean curtailment/cessation of use of antiviral drugs for influenza.

Comparison of continuous and interrupted suture techniques in pyeloplasty: a systematic review and meta-analysis.

Pelvi-ureteric anastomosis is a critical step to ensure good outcome of pyeloplasty. Continuous suturing technique, especially for laparoscopic surgeries, may offer faster operative time while allowing water-tight anastomosis and remains an alternative to interrupted suturing technique. There has been mixed data on comparison of outcomes of continuous and interrupted suturing techniques. This systematic review and meta-analysis aim to assess the outcomes of pyeloplasty based on continuous and interrupted suturing techniques. Following protocol registration on PROSPERO (CRD42021269706), a systematic review was performed in accordance with Cochrane Collaboration. A literature search was performed in September 2021 across Medline, EMBASE, Scopus, Cochrane Library, and ClinicalTrials.gov. Records comparing pyeloplasty outcomes between continuous and interrupted suture techniques were included. Five studies were identified for inclusion (2 prospective, 3 retrospective). Three studies involved pediatric patients. Three studies exclusively assessed laparoscopic technique. Four outcomes were meta-analyzed: operative time, length of stay, complications, and pyeloplasty failure. Interrupted sutures had longer OR time (mean difference 33.14min [95% CI 29.35-36.94], p < 0.0001) and length of stay (mean difference 1.08days [95% CI 0.84-1.32], p < 0.0001). However, there were similar complication (OR 1.73 [95% CI 0.98-3.06], p = 0.06) and failure rates (OR 1.21 [95% CI 0.43-3.43], p = 0.71) between the two suture types. The overall risk of bias in the studies was high. While limited by the number of studies available, continuous sutures for pelvi-ureteric anastomosis appear to confer benefits of faster operative time and decreased length of stay without increasing complication rates or failures.

Empathy in patient-clinician interactions when using telecommunication: A rapid review of the evidence.

ObjectivesThe COVID-19 pandemic accelerated the replacement of many face-to-face healthcare consultations with telephone consultations. Little is known about the extent to which empathy can be expressed in telephone consultations. Our objective is to review evidence related to empathy in telephone consultations including clinical outcomes, and patient/practitioner experiences.MethodsSearches of Medline/Ovid and PsycINFO/Ovid were undertaken. Titles and abstract screening, data extraction, and risk of bias were undertaken by two reviewers. Discrepancies were resolved in discussion with additional reviewers. Included studies were specific to tele-communications with empirical data on empathy related to patient outcomes/views, published (in English), 2010–2021. Studies that did not mention empathy explicitly were excluded.ResultsOur search yielded 740 individual records and 8 studies (527 patients, 20 practitioners) met inclusion criteria: Some barriers to expression of empathy were noted, but no major obstacles were reported. However, data was sparse and most studies had a high risk of bias.ConclusionEmpathy in telephone consultations is possible, (though the loss of non-verbal cues and touch can present barriers) however the research does not yet identify how.InnovationIt is possible to establish and display empathy in telephone consultations, but future research needs to identify how this can be optimized.FundingThis work was supported by a 10.13039/501100000272National Institute for Health Research (NIHR) 10.13039/501100013374School for Primary Care Research grant (project number 389). The 10.13039/501100000739University of Southampton's Primary Care Department is a member of the 10.13039/501100013374NIHR School for Primary Care Research and supported by NIHR Research funds. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Protocol registration.PROSPERO (CRD42021238087).

Comparison of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange and Facemasks in Preoxygenation: A Systematic Review and Meta-Analysis.

Background Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) has received increasing attention and application as an effective noninvasive mode of ventilation in the treatment of clinical anesthesia and critically ill patients. The conclusions reached in clinical studies of THRIVE and facemask oxygenation are still controversial, and the main objective of this systematic review is to determine the advantages of THRIVE over facemask oxygenation in intensive care units, respiratory medicine, and perioperative preoxygenation. Methods PubMed, Embase, Web of Science, and Cochrane Library have search restrictions. The search library was full of English language articles from the first publication to 15 July 2021. Eligible randomized controlled study designs were included. 245 records were screened, and 5 studies met the inclusion criteria, enrolling a total of 235 patients. Results Studying the THRIVE group compared to the facemask group, three studies analyzing intubation time showed that there is no difference in the effect of THRIVE and facemasks (MD -1.22, 95% CI -7.23 to 4.78, and P = 0.69 > 0.05). Three studies analyzing apnea showed that there was no difference between the two groups (SMD 1, 95% CI -0.76 to 2.76, and P = 0.27 > 0.05). Three studies analyzing PaO2 after preoxygenation showed that THRIVE is more effective than facemasks (MD 72.58, 95% CI 31.25 to 113.90, Z = 3.44, and P < 0.001). Two studies analyzing oxygen saturation SpO2 after successful intubation showed that there was no difference in the effectiveness (MD 0.09, 95% CI -1.03 to 1.22, and P = 0.87 > 0.05). Two studies analyzing PCO2 after complete paralysis or intubation preoxygenation showed that there was no difference between the two groups (MD 2.76, 95% CI -1.74 to 7.26, and P = 0.23 > 0.05). Conclusions THRIVE does not have a greater advantage over a facemask in improving apnea time, oxygenation time, PCO2, and SpO2, but it has an advantage in improving arterial partial pressure of oxygen (PaO2) after preoxygenation, which can improve PaO2 well. This trial is registered with the protocol registration number CRD42021268143.

Measuring Quality of Life in Chronic Limb-threatening Ischemia Patients and Informal Carers: A Scoping Review.

To review quality of life (QOL) instruments for chronic limb-threatening ischemia (CLTI) patients and informal carers, and their use in QOL and cost-utility analysis (CUA) studies. CLTI is a global health problem with significant morbidity affecting patients and informal carers. QOL is increasingly measured for holistic outcomes assessment and CUA. However, measurement instruments in CLTI are poorly understood. MEDLINE, EMBASE, PsycINFO, CINAHL, COSMIN, PROQOLID, CEA registry, and NHS EED databases were searched for all English language studies up to May 2021. Features of instruments, evidence of measurement property appraisal, and trends in use were assessed. Prospective protocol registration (Open Science Framework: https://doi.org/10.17605/OSF.IO/KNG9U ). A total of 146 studies on QOL instruments (n=43), QOL outcomes (n=97), and CUA (n=9) were included. Four disease-specific QOL instruments are available for lower extremity arterial disease (intermittent claudication or CLTI). VascuQoL-25 and VascuQoL-6 have been used in CLTI. There is no CLTI-specific instrument. Of 14 generic instruments, SF-36, EQ-5D-3L, NHP, and WHOQOL-BREF were most common. Studies reporting partial measurement property appraisal favored VascuQoL-25, VascuQoL-6, and SF-36. Feasibility considerations include mode of administration and responder burden. None of 4 available carer-specific instruments have been used in CLTI. Since 1992, the number of QOL studies has increased considerably, but CUA studies are scarce. Informal carers have not been assessed. This review provides a comprehensive reference for QOL measurement in CLTI that helps end-users with instrument selection, use, and interpretation. However, a CLTI-specific instrument is needed. There is an opportunity to benefit society through future CUA studies and evaluation of QOL in informal carers.

Baseline health-related quality of life predicts falls: a secondary analysis of a randomized controlled trial.

Among older adults, health-related quality of life (HRQoL) and falls are associated. Generic patient-reported outcomes measures (PROMs) assess individual's HRQoL. The role for PROMs, a potential tool for predicting subsequent falls, remains under-explored. Our primary aim was to determine whether a baseline PROMs assessment of HRQoL may be a useful tool for predicting future falls. A secondary analysis of a 12-month randomized clinical trial (RCT) of a home-based exercise program among 344 adults (67% female), aged ≥ 70years, with ≥ 1 falls in the prior year who were randomized (1:1) to either a home-based exercise program (n = 172) or usual care (n = 172). A negative binomial regression model with total falls count as the dependent variable evaluated the main effect of the independent variable-baseline HRQoL (measured by the Short-Form-6D)-controlling for total exposure time and experiment group (i.e., exercise or usual care) for the total sample. For the usual care group alone, the model controlled for total exposure time. For the total sample, the rate of subsequent total falls was significantly predicted by baseline HRQoL (IRR = 0.044; 95% CI [0.005-0.037]; p = .004). For the usual care group, findings were confirmed with wider confidence intervals and the rate of prospective total falls was significantly predicted by baseline HRQoL (IRR = 0.025; 95% CI [0.001-0.909]; p = .044). These findings suggest the ShortForm-6D should be considered as part of falls prevention screening strategies within a Falls Prevention Clinic setting. Trial Registrations ClinicalTrials.gov Protocol Registration System. Identifier: NCT01029171; URL: https://clinicaltrials.gov/ct2/show/NCT01029171 . Identifier: NCT00323596; URL: https://clinicaltrials.gov/ct2/show/NCT00323596 .

More than one third of clinical practice guidelines on low back pain overlap in AGREE II appraisals. Research wasted?

BackgroundSystematic reviews can apply the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool to critically appraise clinical practice guidelines (CPGs) for treating low back pain (LBP); however, when appraisals differ in CPG quality rating, stakeholders, clinicians, and policy-makers will find it difficult to discern a unique judgement of CPG quality. We wanted to determine the proportion of overlapping CPGs for LBP in appraisals that applied AGREE II. We also compared inter-rater reliability and variability across appraisals.MethodsFor this meta-epidemiological study we searched six databases for appraisals of CPGs for LBP. The general characteristics of the appraisals were collected; the unit of analysis was the CPG evaluated in each appraisal. The inter-rater reliability and the variability of AGREE II domain scores for overall assessment were measured using the intraclass correlation coefficient and descriptive statistics.ResultsOverall, 43 CPGs out of 106 (40.6%) overlapped in seventeen appraisals. Half of the appraisals (53%) reported a protocol registration. Reporting of AGREE II assessment was heterogeneous and generally of poor quality: overall assessment 1 (overall CPG quality) was rated in 11 appraisals (64.7%) and overall assessment 2 (recommendation for use) in four (23.5%). Inter-rater reliability was substantial/perfect in 78.3% of overlapping CPGs. The domains with most variability were Domain 6 (mean interquartile range [IQR] 38.6), Domain 5 (mean IQR 28.9), and Domain 2 (mean IQR 27.7).ConclusionsMore than one third of CPGs for LBP have been re-appraised in the last six years with CPGs quality confirmed in most assessments. Our findings suggest that before conducting a new appraisal, researchers should check systematic review registers for existing appraisals. Clinicians need to rely on updated CPGs of high quality and confirmed by perfect agreement in multiple appraisals.Trial RegistrationProtocol Registration OSF: https://osf.io/rz7nh/

Knowledge translation in Aboriginal and Torres Strait Islander research contexts in Australia: scoping review protocol

IntroductionKnowledge translation (KT) involves bridging the gaps between research knowledge and research application or practice, by sharing this knowledge with knowledge-users. KT is increasingly being used in research with Indigenous...

Quality of systematic reviews of COVID-19 in people with diabetes: A systematic review

ObjectiveTo investigate the methodological quality of published systematic reviews of factors associated with COVID-19 in people with diabetes. MethodSystematic review with registration protocol in PROSPERO, under the number CRD42020222418. Searches were carried out from October to November 2020 in the databases of the MedLine, Web of Science, Scopus, Lilacs, Embase and Cochrane libraries, in addition to searching the reference list of the selected studies. Systematic review studies with or without meta-analysis and without date and language restrictions were included. Data were extracted in a standardized way and the quality of the studies was assessed using the Assessment of Multiple Systematic Reviews scale. ResultsTwelve reviews, published between 2020 and 2021, with a predominance of the English language, systematic reviews of observational studies with meta-analysis with a sample ranging from six to 83 studies, were included. Regarding financing, most of the study reported did not receive this type of support. Regarding to the assessment of the methodological quality of the studies, three were of moderate quality, five were classified as low quality and three with critically low quality. ConclusionsThe analyzed articles presented a bias in the preparation of reports on their studies, suggesting the need to use mechanisms to improve adherence to the established reporting guidelines and methodological evaluation tools.

P-616 Systematic review and meta-analysis of efficacy and safety of r-FSH biosimilars EMA-approved compared to reference r-FSH (follitropin alfa)

Abstract Study question Are recombinant FSH biosimilars approved by the European Medicines Agency (EMA) comparable in efficacy and safety to the originator follitropin alfa? Summary answer Pooled analysis from studies comparing EMA-approved biosimilars with the reference product did not detect differences in efficacy or safety between these two gonadotropins. What is known already A biosimilar is, according to EMA, a biological medicine highly similar to another already approved (‘reference’), and are approved according to the same standards of quality, safety and efficacy. Their development and approval opens a window of opportunity to make IVF treatments more affordable for the general population. Two previous meta-analysis of phase III non-inferiority randomized controlled trials (RCT) including non EMA-approved rFSH biosimilars (Chua et al., 2021 and Budani et a., 2021) have suggested that pregnancy and live births are lower with biosimilars compared to follitropin alfa. Study design, size, duration Systematic review with meta-analysis following PRISMA guidelines. Participants/materials, setting, methods Databases searched from inception to november 2021 were: PubMed-MEDLINE, WOS, The Cochrane Library, ClinicalTrials.gov, EudraCT and Google Scholar using these keywords: ‘biosimilars’, ‘follitropin alfa’, `originator’ and ‘ovarian stimulation’. RCTs and non-randomized comparative studies were included. Risk of bias was assessed with ROB-2 tool and Newcastle-Ottawa Scale studies. Pooled Odds Ratios (OR) and mean differences (MD) when applicable, with a 95% confidence interval (CI), were calculated. PROSPERO protocol registration has been requested. Main results and the role of chance After the systematic search,five studies were included in the meta-analysis: two phase-III RCT (Strawitzki, 2016 and Rettenbacher, 2015) and three non-randomized comparative studies, one of them prospective (Kaplan 2021) and the other two retrospective (Sprem Goldstajn, 2021 and Van den Haute, 2021) involving 2173 IVF cycles. Risk of bias was low for the two RCT and moderate for the observational studies. The OR of clinical pregnancy was 0.89 (95% CI = 0.74,1.07; I2=0%) and the OR of live birth was 0.86 (95% CI = 0.71,1.04; I2=0%). No differences were observed in the cumulative birth rate either (OR = 0.86; 95% CI = 0.68, 1.09; I2 0%). The total number of oocytes retrieved was similar (MD = 0.25; 95%CI,-0.93, 1.43; I2 79%); as it was the total dose of gonadotropins employed (MD=-19.56; 95% CI, -57.88, 18.76; I2 0%) and the length of the stimulation (MD = 0.12; 95% CI,-0.23, 0.47; I2 80%). The risk of Ovarian Hyperstimulation Syndrome was similar in both cases (OR = 1.36; 95% CI, 0.63, 2.91; I2 21%). Limitations, reasons for caution Main limitations of this meta-analysis include the fact that three of the five included studies are not randomized studies and two of them are retrospective, which can bias the results. Wider implications of the findings This is the first meta-analysis including only results from studies with biosimilars EMA-approved. The results show that there are no differences between the biosimilars and the reference in terms of efficacy or safety. Larger RCTs including patients with different patterns of ovarian response are needed to confirm these findings. Trial registration number Not applicable

P-076 Standard IV cannula aspiration of testicular sperm: A novel, efficient and minimally invasive aspiration technique

Abstract Study question Can we aspirate enough testicular tissue for sperm retrieval in non-obstructive azoospermia (NOA), using a wide bore 14-G Standard IV cannula in comparison to micro-TESE? Summary answer Standard IV cannula Aspiration (SIVCA) can yield an ample amount of testicular tissue sufficient for sperm retrieval through a single puncture site on the scrotum. What is known already The current conventional method of testicular sperm aspiration is fine needle aspiration (FNA). FNA has the advantage of being a cost-effective and minimally invasive procedure compared to open testicular sperm extraction (TESE). But FNA with its conventional 23-G needle may not always yield enough testicular tissue for sperm retrieval. Furthermore, FNA may require multiple punctures on the scrotum to retrieve enough tissues from different areas of the testis. Study design, size, duration A 24 months prospective cohort study conducted at a specialized IVF center. A total of 130 men aged from 22 to 53 years old (35.03 +/- 9.04) with NOA and normal testicular volume (≥ 12ml) were enrolled in the study. The men had testicular biopsies taken at the day of their partners’ ovum pick-up. On each patient, the testes were randomized to undergo SIVCA on one testis followed by micro-TESE on the contralateral testis. Participants/materials, setting, methods After local anesthesia, a wide bore 14-G standard IV cannula was introduced near the lower pole of the testis. The needle was withdrawn and the catheter introduced into the testicular tissue. A 20-ml syringe was secured to the catheter and constant negative pressure applied and secured with a clamp. Back and forth motions were performed covering as many areas of the testis as possible. Micro-TESE was then performed on the contralateral testis. Main results and the role of chance Sperm retrieval rates (SRR) were compared between the two techniques using McNemar χ2 test. A P-value of less than 0.05 was considered to be statistically significant. Out of a total of 130 cases, an adequate tissue sample could successfully be aspirated using SIVCA in 122 cases, showing a 0.93 probability of success. In those 8 cases where SIVCA had not yielded sufficient tissue and were reverted to micro-TESE, 2 cases were positive for sperm retrieval. Whenever tissue aspiration was successful with both methods, both SIVCA and micro-TESE showed similar success rate with respect to SRR (56.2 vs 57.3%; McNemar P = 1.000). Limitations, reasons for caution Both FNA and SIVCA are not easy to perform on small sized testes. Moreover if testicular tissue is fibrotic or sclerotic, it may be difficult to aspirate and micro-TESE would be the ideal choice to yield enough testicular tissue. Further blinded randomized control studies with larger datasets are recommended. Wider implications of the findings The use of a peripheral IV wide bore cannula is suitable for the aspiration of adequate amounts of testicular tissue for sperm searching whilst requiring only a single puncture on the scrotum. We recommend routinely starting off with SIVCA to search for sperm before reverting to micro-TESE. Trial registration number Unique Protocol ID: SIVCA Protocol registration Records number will be made available to the public through the ClinicalTrials.gov web site within 2 to 5 days of today 31/1/2022

Preoperative administration of amoxicillin is not recommended in healthy patients undergoing implant surgery.

Design A multicentre, prospective, randomised, placebo-controlled, double-blinded clinical trial reported the early implant failure and postoperative infections of healthy or relatively healthy patients receiving 2 grams of amoxicillin one hour preoperatively from their scheduled dental implant placement. The registration of the study protocol in EudraCT and Clinical Trials.gov (#NCT03412305) followed the ethical principles of the Declaration of Helsinki and the CONSORT guidelines for clinical trials.Case selection Several trial drugs expired before recruiting the intended 1,000 patients calculated based on previous trials reporting 2% and 5% early implant loss, with and without antibiotic prophylaxis. Thus, the study cohort (age >18 years, not planned for immediate loading, not requiring substantial bone augmentation, with an absence of severe diseases or immunosuppression or immunodeficiency) received 757 implants in total between November 2014 and April 2018, consisting of the prophylactic antibiotic therapy group (patients n = 235) and the placebo group (patients n = 235), with a fair sex distribution and a mean age of 57.4 ± 13.9 years. A computer-generated list of random numbers assisted the randomisation (test or control group) with a block-size six. For the clinical procedures, bone augmentation was limited to autogenous bone chips and bone debris. One- and two-stage surgery protocols were used in maxillary or mandibular single or multiple dental implants. The utilised implant systems were Straumann SLA (Straumann Implants, Switzerland), Astra Tech Dental Implant Systems (Dentsply Sirona, Sweden), Nobel Biocare (Sweden) and Southern Implants (Ltd, South Africa). Chlorhexidine 0.2% was prescribed preoperatively and/or postoperatively. Implant failure was the main measured outcome, whereas postoperative infections and adverse events were the secondary outcomes postoperatively assessed at 7-14-day (first follow-up) and 3-6-month (second follow-up) intervals.Data analysis The sample size calculation (type one error: 0.05; power: 80%) estimated 500 patients in each group. Proportional differences and relative risk (RR) with a 95% confidence interval (CI) were calculated. Implant failure was the dependent variable for the multiple logistic regression (MLR) model examining the indicator variables smoking (yes or no), and age (<50 years; 50-64; and ≥65), as well as the independent variables bone augmentation (yes or no), number of implants (1, 2-3 and ≥4), and treatment group (antibiotic prophylaxis or placebo). P-values <0.05 or 95% CIs for ratios not including one were deemed statistically significant. The analyses were carried out using statistical software for data science (STATA).Results Overall, six (2.5%) and seven patients (3.0%) from the amoxicillin and placebo groups had implant failures, respectively. Thus, the intergroup difference was not significant (RR: 0.85; 95% CI: 0.29-2.48, p = 0.75). Absolute risk reduction was 0.46%, with a number needed to treat (NNT) of 219. In other words, one in every 219 patients will benefit from receiving prophylactic antibiotics. In addition, no variable was associated with implant failure. Two (0.8%) and five patients (2.1%) from the amoxicillin and placebo groups, respectively, had postoperative infections at the first follow-up interval. Thus, the intergroup difference was not significant (RR: 0.29; 95% CI: 0.08-2.01, p = 0.25). Five (2.1%) and seven patients (3.0%) from the amoxicillin and placebo groups, respectively, had postoperative infections at the second follow-up interval. Thus, the intergroup difference was not significant (RR: 0.70; 95% CI: 0.23-2.18, p = 0.54). No adverse events were reported.Conclusion Prophylactic antibiotic treatment for dental implant surgery to prevent implant loss may not be appropriate. Each dose must be prescribed based on evidence-based guidelines to avoid overuse and misuse of antibiotics promoting resistant bacteria.

Effectiveness of root canal instrumentation for the treatment of apical periodontitis: A systematic review and meta-analysis.

The development of endodontic instruments has rapidly advanced, but their impact on endodontic outcome parameters remains unclear. This systematic review aimed to answer the following PICOT questions: In patients with apical periodontitis (P) what is the effectiveness of root canal instrumentation ([Q1] performed with contemporary techniques [I] in comparison with 'traditional' techniques [C]] and ([Q2] performed with contemporary engine-driven NiTi instruments [I] compared with other types of contemporary engine-driven NiTi instruments [with different design and/or technology] [C]) in terms of clinical and patient-related outcomes (O)? After PROSPERO protocol registration, a literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Central Register of Controlled Trials. Grey literature and major journal contents were examined. Two independent reviewers performed the study selection, data extraction and appraisal of included studies. A quantitative meta-analysis was considered, and statistical heterogeneity and overall quality of evidence were assessed. Nine studies were identified showing substantial methodological differences. Five studies addressed PICOT 1 and three PICOT 2, whereas one study aimed both. A random-effects meta-analysis model was considered for the outcome 'radiographic evidence of normal periodontal ligament space or reduction of apical lesion size' (PICOT 1) based on three studies with 332 evaluable participants and showed that contemporary instrumentation was associated with a more favourable outcome (p=.005) compared with root canal preparation with stainless steel instruments (odds ratio=2.07 [95%-confidence interval=1.25-3.44]) with no evidence of statistical heterogeneity (I2 = 0%) but low quality of evidence. Albeit a few studies fulfilled eligible criteria, no study had a low risk of bias. Compelling evidence indicating significantly different outcome rates using different endodontic instruments when treating teeth with apical periodontitis is lacking. In terms of healing, the results of the meta-analysis determined the higher effectiveness of root canal instrumentation performed with contemporary techniques in comparison with conventional stainless steel instruments in patients with apical periodontitis followed for a minimum of 1year with low quality of evidence. No differences could be demonstrated between preparations with traditional stainless steel and contemporary NiTi instruments for other clinical and patient-related outcomes. PROSPERO (CRD42021274642).

CANreduce-SP—adding psychological support to web-based adherence-focused guided self-help for cannabis users: study protocol for a three-arm randomized control trial

BackgroundCannabis is the most-frequently used illicit drug in Europe. Over the last few years in Spain, treatment demand has increased, yet most cannabis users do not seek treatment despite the related problems. A web-based self-help tool, like CANreduce 2.0, could help these users to control their consumption.MethodsThis study protocol describes a three-arm randomized controlled trial (RCT) comparing the effectiveness of three approaches, in terms of reducing cannabis use among problematic cannabis users, the first two treatment arms including the Spanish version of CANreduce 2.0 (an adherence-focused, guidance-enhanced, web-based self-help tool) (1) with and (2) without psychological support; and the third group (3) treatment as usual (TAU). Study hypotheses will be tested concerning the primary outcome: change in the number of days of cannabis use over the previous week, comparing assessments at 6 weeks and 3 and 6 months follow-up between groups and against baseline. Secondary outcomes related to cannabis use will be tested similarly. Mental disorders will be explored as predictors of adherence and outcomes. Analyses will be performed on an intention-to-treat basis, then verified by complete case analyses.DiscussionThis study will test how effective the Spanish version of CANreduce 2.0 (CANreduce-SP) is at reducing both the frequency and quantity of cannabis use in problematic users and whether adding psychological support increases its effectiveness.Trial registrationThis trial is registered with the Clinical Trials Protocol Registration and Results System (PRS) number: NCT04517474. Registered 18 August 2020, (Archived by archive.is https://archive.is/N1Y64). The project commenced in November 2020 and recruitment is anticipated to end by November 2022.

Epithelial Cell Adhesion Molecule-Functionalized Fe3O4@Au Nanoparticles for Coregistered Optoacoustic and Magnetic Resonance Imaging and Photothermal Therapy of Hepatocellular Carcinoma

Early diagnosis and management of hepatocellular carcinoma (HCC) is important for improving the 5-year survival rate. Multimodal imaging is of great significance for obtaining complementary information, improving the efficacy of tumor detection, and monitoring HCC recurrence. The rational development of targeted nanoprobes with excellent performance is of great significance for the accurate diagnosis of HCC and image-guided photothermal therapy (PTT). In the present study, we synthesized a hybrid nanoprobe containing epithelial cell adhesion molecule-functionalized Fe3O4@Au nanoparticles as an HCC-targeted nanoprobe, which served as a dual-modal contrast agent for optoacoustic tomography (OAT) and magnetic resonance imaging (MRI) and as a photothermal sensitizer for PTT. Using this nanoprobe, we evaluated the application of coregistered OAT–MRI for the diagnosis and therapy of HCC to resolve an image alignment problem. Body-position variation in OAT and MRI was minimized using a specially designed 3D-printed dual-modality animal imaging bed constructed from polylactic acid. The registration accuracy of OAT–MRI data was further improved by a robust image registration protocol. Dual-modality coregistered imaging was performed for the early diagnosis of HCC and monitoring of curative effects. To our knowledge, this is the first study to apply a combination of a targeted nanoprobe and coregistration of OAT–MRI for the diagnosis and management of abdominal diseases.

Effectiveness of a brief hope intervention for chronic kidney disease patients on the decisional conflict and quality of life: a pilot randomized controlled trial

BackgroundStage 5 chronic kidney disease (CKD) patients often experience decisional conflict when faced with the selection between the initiation of dialysis and conservative care. The study examined the effects of a brief hope intervention (BHI) on the levels of hope, decisional conflict and the quality of life for stage 5 CKD patients.MethodsThis is a single-blinded, randomized controlled trial (ClinicalTrials.gov identifier: NCT03378700). Eligible patients were recruited from the outpatient department renal clinic of a regional hospital. They were randomly assigned to either the intervention or the control group (intervention: n = 35; control: n = 37). All participants underwent a customized pre-dialysis education class, while the intervention group received also BHI. Data were collected prior to the intervention, immediately afterwards, and one month following the intervention. The Generalized Estimating Equation was used to measure the effects in the level of hope, decisional conflict scores (DCS) and Kidney Disease Quality of life (KDQOL-36) scores. Estimated marginal means and standard errors with 95% confidence intervals of these scores were also reported to examine the within group and between group changes.ResultsAn increase of the hope score was found from time 1 (29.7, 1.64) to time 3 (34.4, 1.27) in the intervention group. The intervention had a significant effect on the KDQOL-36 sub-scores Mental Component Summary (MCS) (Wald χ2 = 6.763, P = 0.009) and effects of kidney disease (Wald χ2 = 3.617, P = 0.004). There was a reduction in decisional conflict in both arms on the DCS total score (Wald χ2 = 7.885, P = 0.005), but the reduction was significantly greater in the control group (effect size 0.64).ConclusionsThe BHI appeared to increase the level of hope within the intervention arm. Nonetheless, differences across the intervention and control arms were not significant. The KDQOL-36 sub-scores on MCS and Effects of kidney disease were found to have increased and be higher in the intervention group. The DCS total score also showed that hope was associated with reducing decisional conflict.Trial RegistrationClinicalTrials.gov Protocol Registration, NCT03378700. Registered July 12 2017.

A scoping review of online international student collaboration in occupational therapy education

Introduction For occupational therapy students, international experiences and access to a global curriculum develops understanding of broad cultural and contextual determinants of health and wellbeing. International placements or study abroad opportunities are not possible for many students and many universities are developing alternative internationalisation opportunities. The aim of this review was to determine what is known from the existing literature on the use of online international student collaboration in occupational therapy curricula. Method A scoping review design was used to search relevant literature on online international student collaboration in occupational therapy education, following a methodological framework for conducting scoping reviews. Seven databases were searched. Search included all articles published up until November 2020. Findings The database searches yielded a total of 2011 results. Following screening and review of articles ten papers met the inclusion criteria and were included in the review. The studies were charted and discussed in the areas of format of the online interactions, reported outcomes of the online interactions, barriers and facilitators in implementation. Conclusion Findings inform curricula designers establishing online international learning and those conducting research in this area. Outcomes indicate the breadth of student learning including culture, diversity, as well as the social determinants of occupational engagement and participation. Registration Protocol Registered: 2020-07-06, available on Open Science Framework (OSF) at https://osf.io/wfkjy

Teaching evidence-based medicine in Mexico: a systematic review of medical doctor curriculums at a national level

ObjectivesTo assess the teaching of evidence-based medicine (EBM) in medical curriculums. As a secondary objective, we assessed the representativeness of science courses related to EBM.Design and settingSystematic review. Accredited curriculums...

The effect of olive leaf use on blood pressure; A systematic review and meta-analysis

Context: Hypertension has been identified as the world’s third leading cause of death. Due to their cost-effectiveness and lack of adverse effects compared to antihypertensive medications, medicinal plants have gained popularity in most countries. The olive leaf is one of these plants. As a result, the purpose of the current systematic review and meta-analysis was to determine the effect of olive leaf consumption on systolic and diastolic blood pressure. Evidence acquisition: The following domestic and international databases were searched in order to retrieve relevant studies: PubMed, Scopus, Web of Science, Embase, Cochrane, ProQuest, and Google Scholar search engine, the ClinicalTrials.gov Protocol Registration and Results System (PRS), the ISRCTN registry administered by BioMed Central, and the World Health Organization’s (WHO) International Clinical Trials Registry Platform. The data collected were analyzed using STATA software (version14) at a significance level of P&lt;0.05. Results: Olive leaf consumption had a significant effect on systolic blood pressure [-0.87 (95% CI: -1.09, -0.64)] and diastolic blood pressure [-0.39 (95% CI: -0.57, -0.21)] in five studies with a sample size of 145 people (mean age range of 33.30 ± 5.25 years). Consumption of olive leaves also decreased cholesterol levels [-0.52 (95% CI: -0.81, -0.22)], low-density lipoprotein (LDL-c) levels [-0.35 (95% CI: -0.58, -0.12)], and triglycerides levels [-0.67 (95% CI: -1.19, -0.16)]. Nonetheless, the olive leaf had no statistically significant effect on reducing highdensity lipoprotein levels. Conclusion: We observed that olive leaf consumption significantly reduced the levels of systolic and diastolic blood pressure, cholesterol, triglycerides, and LDL-c. Registration: The current protocol was also registered on PROSPERO (ID: 221277, Date: 16.04.2022).