Transitivity, coherence, and reliability of network meta-analyses comparing proximal humerus fracture treatments: a meta-epidemiological study.

BACKGROUND: Network meta-analyses can be valuable for decision-makers in guiding clinical practice. However, for network meta-analysis results to be reliable, the assumptions of both transitivity and coherence must be met, and the methodology should adhere to current best practices. We aimed to assess whether network meta-analyses of randomized controlled trials (RCTs) comparing interventions for proximal humerus fractures provide reliable estimates of intervention effects. METHODS: We searched PubMed, EMBASE, The Cochrane Library, and Web of Science for network meta-analyses comparing interventions for proximal humerus fractures. We critically assessed the methodology regarding the development of a protocol, search strategy, trial inclusion, outcome extraction, and the methods used to conduct the network meta-analyses. We assessed the transitivity and coherence of the network graphs for the Constant score (CS), Disabilities of the Arm, Shoulder, and Hand score (DASH), and additional surgery. Transitivity was assessed by comparing probable effect modifiers (age, gender, fracture morphology, and comorbidities) across intervention comparisons. Coherence was assessed using Separating Indirect from Direct Evidence (SIDE) (Separating Indirect from Direct Evidence) and the design-by-treatment interaction test. We used CINeMA (Confidence in Network Meta-analyses) to assess the confidence in the results. RESULTS: None of the three included network meta-analyses had a publicly available protocol or data-analysis plan, and they all had methodological flaws that could threaten the validity of their results. Although we did not detect incoherence for most comparisons, the transitivity assumption was violated for CS, DASH, and additional surgery in all three network meta-analyses. Additionally, the confidence in the results was 'very low' primarily due to within-study bias, reporting bias, intransitivity, imprecision, and heterogeneity. CONCLUSIONS: Current network meta-analyses of RCTs comparing interventions for proximal humerus fractures do not provide reliable estimates of intervention effects. We advise caution in using these network meta-analyses to guide clinical practice. To improve the utility of network meta-analyses to guide clinical practice, journal editors should require that network meta-analyses are done according to a predefined analysis plan in a publicly available protocol and that both coherence and transitivity have been adequately assessed and reported.

Immediate Postpartum Breastfeeding Following Pregnancy with Cardiac Disease.

OBJECTIVE: This study aimed to identify predictors of immediate postpartum breastfeeding among women with maternal cardiac disease (MCD). STUDY DESIGN: This study included all gravidas with MCD who delivered at a single institution from 2012 to 2018. Charts were abstracted for maternal demographics, obstetrical outcome, cardiac diagnoses, cardiac risk stratification scores, and prepregnancy echocardiogram findings. Kruskal-Wallis and Fisher's exact tests were used to compare the breastfeeding (BF) group versus the nonbreastfeeding (NBF) group. Logistic regression was used to obtain odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Among 211 gravidas with MCD, 12% were not breastfeeding at the time of postpartum hospital discharge. Compared with the BF group, the NBF group had a significantly higher proportion of women with cardiomyopathy (21% NBF vs. 7% BF, OR 3.44, 95% CI 1.12-10.71), with modified World Health Organization (WHO) classification ≥III (33 vs. 14%, OR 3.16, 95% CI 1.22-8.15), and with prepregnancy ejection fraction (EF) < 50% (55 vs. 14%, OR 7.20, 95% CI 1.92-27.06). There were otherwise no differences between the two groups with regards to other cardiac diagnoses or cardiac risk scores. CONCLUSION: In women with MCD, cardiomyopathy, modified WHO class ≥III, and a prepregnancy EF < 50% were associated with NBF in the immediate postpartum period. These findings may guide providers in identifying a subset of women with MCD who can benefit from increased breastfeeding counseling and support. KEY POINTS: · Eighty-two percent of patients with cardiac disease are breastfeeding at the time of postpartum discharge.. · Cardiomyopathy is associated with an increased odds of not breastfeeding at postpartum discharge.. · Rationale for not breastfeeding is infrequently documented in the medical record..

The Impact of Surgical Approach on 90-Day Prosthetic Joint Infection After Total Hip Replacement - A Population-Based, Propensity Score-Matched Cohort Study.

BACKGROUND: Prosthetic joint infection (PJI) is a devastating complication of total hip arthroplasty (THA). This study aimed to determine if the anterior approach (AP) influenced the incidence of early PJI in THA compared to posterior approach (PP). METHODS: Record linkage was performed between state-wide hospitalization data and a national joint replacement registry to identify unilateral THA performed via the AP or PP. Complete data on 12,605 AP and 25,569 PP THAs were obtained. Propensity score matching (PSM) was undertaken to match covariates between the approaches. Outcomes were the 90-day PJI hospital readmission rate(using narrow and broad definitions) and 90-day PJI revision rate (defined as component removal or exchange). RESULTS: The raw PJI readmission rate for AP was lower than PP (0.8% versus 1.1%, respectively). In the PSM analysis, there was no statistically significant difference in PJI readmission rate between approaches using narrow or broad definition of PJI readmission. In terms of revision for infection, both methods showed AP had a significantly lower rate than PP, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval (CI) 0.30, 0.75) for the 1:1 nearest neighbor method and 0.50 (95% CI 0.32, 0.77) for the subclassification method. CONCLUSION: After addressing known confounders, there was no significant difference in the 90-day hospital readmission rate for hip PJI between approaches. There was a significantly reduced 90-day PJI revision rate for AP. The difference in revision may reflect differences in the surgical management of PJI between hip approaches rather than a difference in the underlying rate of infection.

Aspirin as Venous Thromboembolism Prophylaxis in Arthroplasty Patients: An Analysis of Clinical Practice Guidelines Recommendations.

BACKGROUND: Venous thromboembolism (VTE) is a recognized postoperative complication of hip or knee arthroplasty and incurs major morbidity and mortality. While anticoagulants are the mainstay of chemoprophylaxis, aspirin has recently emerged as a popular prophylactic agent. However, there is a lack of high-quality evidence comparing aspirin to anticoagulants as a method of VTE prophylaxis, and current guidelines are conflicting regarding using aspirin as first-line chemoprophylaxis. We aimed to investigate guideline characteristics that are associated with the recommendation for or against aspirin as a first-line agent. METHODS: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and PubMed databases were searched from 1966 to January 2024 to identify clinical practice guidelines for VTE prophylaxis in adult hip or knee arthroplasty inpatients of average risk. The characteristics of the guideline were collected by 2 independent reviewers. Logistic regression was used to test the association between the recommendation for or against aspirin and guideline characteristics. RESULTS: There were 26 guidelines published from February 2003 to September 2023 and included in this study. There were 5 guidelines that recommended aspirin and 11 guidelines that recommended against aspirin as first-line therapy. With a more recent year of publication, aspirin was more likely to be recommended (odds ratio 1.72, 95% confidence interval: 1.05 to 2.84) and less likely to be recommended against (odds ratio 0.61, 95% confidence interval: 0.41 to 0.90). No other variables, including the level of evidence used, the composition of the guideline working group, or the objective of the guideline, were associated with the recommendation for or against aspirin. CONCLUSIONS: Guidelines were inconsistent in their recommendations regarding aspirin as first-line therapy as VTE prophylaxis in arthroplasty patients. Adequately powered randomized controlled trials using modern practices, such as early postoperative mobilization, are needed to better inform clinical practice guidelines.

Stemmed Tibial Fixation for Primary Total Knee Arthroplasty in Obese Patients-A National Registry Study.

BACKGROUND: We investigated if the use of augmented tibial fixation with stems in primary total knee arthroplasty (TKA) in obese patients was associated with a difference in reason for revision, type of revision, or overall revision rate. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry compared reason for revision, rate, and type of revision between primary TKA using stemmed tibial prostheses to nonstemmed prostheses, stratified by body mass index (BMI) and obesity. The cumulative percent revision was obtained using the Kaplan-Meier method, and Cox proportional hazards models estimated hazard ratios (HRs) adjusted for age and sex with 95% confidence intervals (CIs). All tests were 2-tailed at 5% statistical significance (P < .05). There were 66,508 procedures available for analyses. RESULTS: Obese class 2 (BMI 35 to 39.99) had higher rates of revision in the stemmed group compared to the nonstemmed group (HR 1.44, 95% CI 1.00, 2.05, P = .047). There was no significant difference in revision rates between stemmed and nonstemmed tibial prostheses in any other BMI group. Primary TKA in obese patients (BMI ≥30) with a stem extension had a significantly higher rate of minor revisions compared to no stem extension (HR 1.31, 95% CI 1.03, 1.66, P = .025). There was no significant difference between stemmed and nonstemmed groups for major revision in obese patients and for minor or major revision in nonobese patients. CONCLUSION: Using a tibial stem during primary TKA in obese patients is not associated with a lower rate of revision.

Utilizing Stems in Primary Total Knee Arthroplasty: Analysis of the Australian Orthopaedic Association National Joint Replacement Registry Data.

BACKGROUND: We compared revision rates and reasons for revision for primary total knee arthroplasty (TKA) performed for osteoarthritis with and without tibial stem extensions. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were used to compare all-cause revision, reason, and type of revision between primary TKA using stemmed tibial prostheses and non-stemmed prostheses. RESULTS: All-cause revision for TKA with stem extension was higher for the first 6 months (hazard ratio [HR] 1.47; 95% confidence interval [CI]1.19 to 1.82; P < .001); while after 1.5 years TKA with stem extension had a lower rate of revision (HR 0.84; 95% CI 0.73 to 0.97; P = .01). Stemmed components were more likely to be revised for infection between 3 months and 1.5 years after surgery (HR 1.39; 95% CI 1.05 to 1.83; P = .02). The revision rate for aseptic loosening was lower in the stemmed group beyond 2 years (HR = 0.45; 95% CI 0.31 to 0.63; P < .001). Insert-only revision was higher in the stemmed group at all times (HR = 1.42; 95% CI 1.21 to 1.66, P < .001). Isolated tibial component revision was lower in the stemmed group at all times (HR 0.47; 95% CI 0.29 to 0.74; P = .001). Aseptic loosening for tibial component-only revision was significantly lower in the stemmed group at all times (HR 0.23; 95% CI 0.11 to 0.50; P < .001). CONCLUSIONS: Patients undergoing primary stemmed TKA have lower rates of all-cause revision beyond 1.5 years and tibial component-only revision at all times. Further investigation is required to preoperatively select patients that benefit from augmentation with stems.

A systematic review and meta-analysis of short-stay programmes for total hip and knee replacement, focusing on safety and optimal patient selection.

BACKGROUND: Short-stay joint replacement programmes are used in many countries but there has been little scrutiny of safety outcomes in the literature. We aimed to systematically review evidence on the safety of short-stay programmes versus usual care for total hip (THR) and knee replacement (KR), and optimal patient selection. METHODS: A systematic review and meta-analysis. Randomised controlled trials (RCTs) and quasi-experimental studies including a comparator group reporting on 14 safety outcomes (hospital readmissions, reoperations, blood loss, emergency department visits, infection, mortality, neurovascular injury, other complications, periprosthetic fractures, postoperative falls, venous thromboembolism, wound complications, dislocation, stiffness) within 90 days postoperatively in adults ≥ 18 years undergoing primary THR or KR were included. Secondary outcomes were associations between patient demographics or clinical characteristics and patient outcomes. Four databases were searched between January 2000 and May 2023. Risk of bias and certainty of the evidence were assessed. RESULTS: Forty-nine studies were included. Based upon low certainty RCT evidence, short-stay programmes may not reduce readmission (OR 0.95, 95% CI 0.12-7.43); blood transfusion requirements (OR 1.75, 95% CI 0.27-11.36); neurovascular injury (OR 0.31, 95% CI 0.01-7.92); other complications (OR 0.63, 95% CI 0.26-1.53); or stiffness (OR 1.04, 95% CI 0.53-2.05). For registry studies, there was no difference in readmission, infection, neurovascular injury, other complications, venous thromboembolism, or wound complications but there were reductions in mortality and dislocations. For interrupted time series studies, there was no difference in readmissions, reoperations, blood loss volume, emergency department visits, infection, mortality, or neurovascular injury; reduced odds of blood transfusion and other complications, but increased odds of periprosthetic fracture. For other observational studies, there was an increased risk of readmission, no difference in blood loss volume, infection, other complications, or wound complications, reduced odds of requiring blood transfusion, reduced mortality, and reduced venous thromboembolism. One study examined an outcome relevant to optimal patient selection; it reported comparable blood loss for short-stay male and female participants (p = 0.814). CONCLUSIONS: There is low certainty evidence that short-stay programmes for THR and KR may have non-inferior 90-day safety outcomes. There is little evidence on factors informing optimal patient selection; this remains an important knowledge gap.

Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors.

Vascular development begins when mesodermal cells differentiate into endothelial cells, which then form primitive vessels. It has been hypothesized that endothelial-specific gene expression may be regulated combinatorially, but the transcriptional mechanisms governing specificity in vascular gene expression remain incompletely understood. Here, we identify a 44 bp transcriptional enhancer that is sufficient to direct expression specifically and exclusively to the developing vascular endothelium. This enhancer is regulated by a composite cis-acting element, the FOX:ETS motif, which is bound and synergistically activated by Forkhead and Ets transcription factors. We demonstrate that coexpression of the Forkhead protein FoxC2 and the Ets protein Etv2 induces ectopic expression of vascular genes in Xenopus embryos, and that combinatorial knockdown of the orthologous genes in zebrafish embryos disrupts vascular development. Finally, we show that FOX:ETS motifs are present in many known endothelial-specific enhancers and that this motif is an efficient predictor of endothelial enhancers in the human genome.

Elective spinal surgery in New South Wales adults, 2001-20, by procedure funding type: a cross-sectional study.

OBJECTIVE: To investigate elective rates of spinal fusion, decompression, and disc replacement procedures for people with degenerative conditions, by funding type (public, private, workers' compensation). DESIGN, SETTING: Cross-sectional study; analysis of hospitals admissions data extracted from the New South Wales Admitted Patient Data Collection. PARTICIPANTS: All adults who underwent elective spinal surgery (spinal fusion, decompression, disc replacement) in NSW, 1 July 2001 - 30 June 2020. MAIN OUTCOME MEASURES: Crude and age- and sex-adjusted procedure rates, by procedure, funding type, and year; annual change in rates, 2001-20, expressed as incidence rate ratios (IRRs). RESULTS: During 2001-20, 155 088 procedures in 129 525 adults were eligible for our analysis: 53 606 fusion, 100 225 decompression, and 1257 disc replacement procedures. The privately funded fusion procedure rate increased from 26.6 to 109.5 per 100 000 insured adults (per year: IRR, 1.06; 95% confidence interval [CI], 1.05-1.07); the workers' compensation procedure rate increased from 6.1 to 15.8 per 100 000 covered adults (IRR, 1.04; 95% CI, 1.01-1.06); the publicly funded procedure rate increased from 5.6 to 12.4 per 100 000 adults (IRR, 1.03; 95% CI, 1.01-1.06), and from 10.5 to 22.1 per 100 000 adults without hospital cover private health insurance (IRR, 1.03; 95% CI, 1.01-1.05). The privately funded decompression procedure rate increased from 93.4 to 153.6 per 100 000 people (IRR, 1.02; 95% CI, 1.01-1.03); the workers' compensation procedure rate declined from 19.7 to 16.7 per 100 000 people (IRR, 0.98; 95% CI, 0.96-0.99), and the publicly funded procedure rate did not change significantly. The privately funded disc replacement procedure rate increased from 6.2 per million in 2010-11 to 38.4 per million people in 2019-20, but did not significantly change for the other two funding groups. The age- and sex-adjusted rates for privately and publicly funded fusion and decompression procedures were similar to the crude rates. CONCLUSIONS: Privately funded spinal surgery rates continue to be larger than for publicly funded procedures, and they have also increased more rapidly. These differences may indicate that some privately funded procedures are unnecessary, or that the number of publicly funded procedures does not reflect clinical need.

Cryotherapy following total knee replacement.

BACKGROUND: Total knee replacement (TKR) is a common intervention for people with end-stage symptomatic knee osteoarthritis, resulting in significant improvements in pain, function and quality of life within three to six months. It is, however, acutely associated with pain, local oedema and blood loss. Post-operative management may include cryotherapy. This is the application of low temperatures to the skin surrounding the surgical site, through ice or cooled water, often delivered using specialised devices. This is an update of a review published in 2012. OBJECTIVES: To evaluate the effect of cryotherapy in the acute phase after TKR (within 48 hours after surgery) on blood loss, pain, transfusion rate, range of motion, knee function, adverse events and withdrawals due to adverse events. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases and two trials registers, as well as reference lists, related links and conference proceedings on 27 May 2022. SELECTION CRITERIA: We included randomised controlled trials or controlled clinical trials comparing cryotherapy with or without other treatments (such as compression, regional nerve block or continuous passive motion) to no treatment, or the other treatment alone, following TKR for osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and assessed risk of bias and certainty of evidence using GRADE. We discussed any disagreements and consulted another review author to resolve them, if required. Major outcomes were blood loss, pain, transfusion rate, knee range of motion, knee function, total adverse events and withdrawals from adverse events. Minor outcomes were analgesia use, knee swelling, length of stay, quality of life, activity level and participant-reported global assessment of success. MAIN RESULTS: We included 22 trials (20 randomised trials and two controlled clinical trials), with 1839 total participants. The mean ages reflected the TKR population, ranging from 64 to 74 years. Cryotherapy with compression was compared to no treatment in four studies, and to compression alone in nine studies. Cryotherapy without compression was compared to no treatment in eight studies. One study compared cryotherapy without compression to control with compression alone. We combined all control interventions in the primary analysis. Certainty of evidence was low for blood loss (downgraded for bias and inconsistency), pain (downgraded twice for bias) and range of motion (downgraded for bias and indirectness). It was very low for transfusion rate (downgraded for bias, inconsistency and imprecision), function (downgraded twice for bias and once for inconsistency), total adverse events (downgraded for bias, indirectness and imprecision) and withdrawals from adverse events (downgraded for bias, indirectness and imprecision). The nature of cryotherapy made blinding difficult and most studies had a high risk of performance and detection bias. Low-certainty evidence from 12 trials (956 participants) shows that cryotherapy may reduce blood loss at one to 13 days after surgery. Blood loss was 825 mL with no cryotherapy and 561 mL with cryotherapy: mean difference (MD) 264 mL less (95% confidence interval (CI) 7 mL less to 516 mL less). Low-certainty evidence from six trials (530 participants) shows that cryotherapy may slightly improve pain at 48 hours on a 0- to 10-point visual analogue scale (lower scores indicate less pain). Pain was 4.8 points with no cryotherapy and 3.16 points with cryotherapy: MD 1.6 points lower (95% CI 2.3 lower to 1.0 lower). We are uncertain whether cryotherapy improves transfusion rate at zero to 13 days after surgery. The transfusion rate was 37% with no cryotherapy and 79% with cryotherapy (risk ratio (RR) 2.13, 95% CI 0.04 to 109.63; 2 trials, 91 participants; very low-certainty evidence). Low-certainty evidence from three trials (174 participants) indicates cryotherapy may improve range of motion at discharge: it was 62.9 degrees with no cryotherapy and 71.2 degrees with cryotherapy: MD 8.3 degrees greater (95% CI 3.6 degrees more to 13.1 degrees more). We are uncertain whether cryotherapy improves function two weeks after surgery. Function was 75.4 points on the 0- to 100-point Dutch Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale (lower score indicates worse function) in the control group and 88.6 points with cryotherapy (MD 13.2 points better, 95% CI 0.5 worse to 27.1 improved; 4 trials, 296 participants; very low-certainty evidence). We are uncertain whether cryotherapy reduces total adverse events: the risk ratio was 1.30 (95% CI 0.53 to 3.20; 16 trials, 1199 participants; very low-certainty evidence). Adverse events included discomfort, local skin reactions, superficial infections, cold-induced injuries and thrombolytic events. We are uncertain whether cryotherapy reduces withdrawals from adverse events (RR 2.71, 95% CI 0.42 to 17.38; 19 trials, 1347 participants; very low-certainty evidence). No significant benefit was found for secondary outcomes of analgesia use, length of stay, activity level or quality of life. Evidence from seven studies (403 participants) showed improved mid-patella swelling between two and six days after surgery (MD 7.32 mm less, 95% CI 11.79 to 2.84 lower), though not at six weeks and three months after surgery. The included studies did not assess participant-reported global assessment of success. AUTHORS' CONCLUSIONS: The certainty of evidence was low for blood loss, pain and range of motion, and very low for transfusion rate, function, total adverse events and withdrawals from adverse events. We are uncertain whether cryotherapy improves transfusion rate, function, total adverse events or withdrawals from adverse events. We downgraded evidence for bias, indirectness, imprecision and inconsistency. Hence, the potential benefits of cryotherapy on blood loss, pain and range of motion may be too small to justify its use. More well-designed randomised controlled trials focusing especially on clinically meaningful outcomes, such as blood transfusion, and patient-reported outcomes, such as knee function, quality of life, activity level and participant-reported global assessment of success, are required.

Spinal cord stimulation for low back pain.

BACKGROUND: Spinal cord stimulation (SCS) is a surgical intervention used to treat persistent low back pain. SCS is thought to modulate pain by sending electrical signals via implanted electrodes into the spinal cord. The long term benefits and harms of SCS for people with low back pain are uncertain. OBJECTIVES: To assess the effects, including benefits and harms, of SCS for people with low back pain. SEARCH METHODS: On 10 June 2022, we searched CENTRAL, MEDLINE, Embase, and one other database for published trials. We also searched three clinical trials registers for ongoing trials. SELECTION CRITERIA: We included all randomised controlled trials and cross-over trials comparing SCS with placebo or no treatment for low back pain. The primary comparison was SCS versus placebo, at the longest time point measured in the trials. Major outcomes were mean low back pain intensity, function, health-related quality of life, global assessment of efficacy, withdrawals due to adverse events, adverse events, and serious adverse events. Our primary time point was long-term follow-up (≥ 12 months). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 13 studies with 699 participants: 55% of participants were female; mean age ranged from 47 to 59 years; and all participants had chronic low back pain with mean duration of symptoms ranging from five to 12 years. Ten cross-over trials compared SCS with placebo. Three parallel-group trials assessed the addition of SCS to medical management. Most studies were at risk of performance and detection bias from inadequate blinding and selective reporting bias. The placebo-controlled trials had other important biases, including lack of accounting for period and carryover effects. Two of the three parallel trials assessing SCS as an addition to medical management were at risk of attrition bias, and all three had substantial cross-over to the SCS group for time points beyond six months. In the parallel-group trials, we considered the lack of placebo control to be an important source of bias. None of our included studies evaluated the impact of SCS on mean low back pain intensity in the long term (≥ 12 months). The studies most often assessed outcomes in the immediate term (less than one month). At six months, the only available evidence was from a single cross-over trial (50 participants). There was moderate-certainty evidence that SCS probably does not improve back or leg pain, function, or quality of life compared with placebo. Pain was 61 points (on a 0- to 100-point scale, 0 = no pain) at six months with placebo, and 4 points better (8.2 points better to 0.2 points worse) with SCS. Function was 35.4 points (on a 0- to 100-point scale, 0 = no disability or best function) at six months with placebo, and 1.3 points better (3.9 points better to 1.3 points worse) with SCS. Health-related quality of life was 0.44 points out of 1 (0 to 1 index, 0 = worst quality of life) at six months with placebo, and 0.04 points better (0.16 points better to 0.08 points worse) with SCS. In that same study, nine participants (18%) experienced adverse events and four (8%) required revision surgery. Serious adverse events with SCS included infections, neurological damage, and lead migration requiring repeated surgery. We could not provide effect estimates of the relative risks as events were not reported for the placebo period. In parallel trials assessing SCS as an addition to medical management, it is uncertain whether, in the medium or long term, SCS can reduce low back pain, leg pain, or health-related quality of life, or if it increases the number of people reporting a 50% improvement or better, because the certainty of the evidence was very low. Low-certainty evidence suggests that adding SCS to medical management may slightly improve function and slightly reduce opioid use. In the medium term, mean function (0- to 100-point scale; lower is better) was 16.2 points better with the addition of SCS to medical management compared with medical management alone (95% confidence interval (CI) 19.4 points better to 13.0 points better; I2 = 95%; 3 studies, 430 participants; low-certainty evidence). The number of participants reporting opioid medicine use was 15% lower with the addition of SCS to medical management (95% CI 27% lower to 0% lower; I2 = 0%; 2 studies, 290 participants; low-certainty evidence). Adverse events with SCS were poorly reported but included infection and lead migration. One study found that, at 24 months, 13 of 42 people (31%) receiving SCS required revision surgery. It is uncertain to what extent the addition of SCS to medical management increases the risk of withdrawals due to adverse events, adverse events, or serious adverse events, because the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: Data in this review do not support the use of SCS to manage low back pain outside a clinical trial. Current evidence suggests SCS probably does not have sustained clinical benefits that would outweigh the costs and risks of this surgical intervention.

The effect of ketamine and fentanyl on haemodynamics during intubation in pre-hospital and retrieval medicine.

BACKGROUND: Ketamine use for rapid sequence intubation (RSI) is frequent in pre-hospital and retrieval medicine (PHARM) and is associated with potentially deleterious haemodynamic changes, which may be ameliorated by concurrent use of fentanyl. OBJECTIVES: To describe the frequency with which fentanyl is used in conjunction with ketamine in a system where its use is discretionary, and to explore any observed changes in haemodynamics with its use. METHODS: A retrospective observational study of over 800 patients undergoing RSI with ketamine ± fentanyl in the PHARM setting between 2015 and 2019. The primary outcome was the proportion of patients in each group who had a systolic blood pressure (SBP) outside a pre-specified target range, with adjustment for baseline abnormality, within 10 min of anaesthetic induction. RESULTS: Eight hundred and seventy-six patients were anaesthetised with ketamine, of whom 804 were included in the analysis. 669 (83%, 95% CI 80%-86%) received ketamine alone, and 135 (17%, 95% CI 14%-20%) received both fentanyl and ketamine. Median fentanyl dose was 1.1 mcg/kg (IQR 0.75-1.5 mcg/kg). Systolic blood pressure (SBP) at induction was consistently associated with SBP after intubation in multivariable logistic regression, but fentanyl use was not associated with a change in odds of meeting the primary outcome (OR 1.08; 95% CI 0.72-1.60), becoming hypertensive (OR 1.35; 95% CI 0.88-2.07) or hypotensive (OR 0.76; 95% CI 0.47-1.21). CONCLUSIONS: The addition of fentanyl to ketamine for RSI was not associated with an alteration of the odds of post-induction haemodynamic stability, although the doses used were low. These findings justify further study into the optimal dosing of fentanyl during RSI in pre-hospital and retrieval medicine.

Stakeholder perspectives on short-stay joint replacement programs: results from a national cross-sectional study.

BACKGROUND: The capacity to meet anticipated growth in joint replacement demand requires safe, efficient models of care. While short-stay joint replacement programs are being used internationally, they have not been widely implemented in many countries. Importantly, the critical challenges that need to be addressed ahead of large-scale program implementation remain unclear. This study aimed to investigate stakeholder perspectives on short-stay joint replacement programs, including perceived barriers and enablers to implementation and sustainability, and understand current practices in Australia. METHODS: Four key stakeholder groups were invited to participate in this national study: (1) health professionals who provide joint replacement care; (2) hospital administrators involved in joint replacement provision; (3) patients with recent joint replacement; and (4) carers of people with recent joint replacement. Data on perceived feasibility (0 (not at all feasible) - 10 (highly feasible), appeal (0 (not at all appealing) - 10 (highly appealing), current practices, and barriers and enablers were collected using visual analogue scales, multiple response option and open-ended questions, via an online platform. Descriptive analysis and free-text content analysis was undertaken. RESULTS: Data were available from 1,445 participants including 360 health professionals, 20 hospital administrators, 1,034 patients, and 31 carers. Short-stay program implementation was considered moderately feasible by health professionals (median 6, interquartile range (IQR) 3-8) and hospital administrators (median 5, IQR 5-6). Short-stay programs were moderately appealing to patients (median 7, IQR 2-9) but of little appeal to carers (median 3, IQR 1-7). Prominent implementation barriers included perceived limited appropriateness of short-stay programs, inadequate home supports, and issues around reimbursement models or program funding. Not having daily physiotherapy access and concerns about pain and mobility at home were common barriers for patients. Concern about patients' ability to manage daily activities was the most common barrier for carers. Access to post-discharge services, better funding models, improved staffing, and consistent protocols and national care standards were prominent enablers. CONCLUSIONS: This national study has uniquely captured multiple stakeholder perspectives on short-stay joint replacement programs. The findings can guide future quality improvement and implementation initiatives and the development of resources to best support patients, carers, clinicians, and hospitals.

Do the Revision Rates of Arthroplasty Surgeons Correlate With Postoperative Patient-reported Outcome Measure Scores? A Study From the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: Patient-reported outcome measures (PROMs) are a pragmatic and efficient means to evaluate the functional quality of arthroplasty beyond revision rates, which are used by most joint replacement registries to judge success. The relationship between these two measures of quality-revision rates and PROMs-is unknown, and not every procedure with a poor functional result is revised. It is logical-although still untested-that higher cumulative revision rates correlate inversely with PROMs for individual surgeons; more revisions are associated with lower PROM scores. QUESTIONS/PURPOSES: We used data from a large national joint replacement registry to ask: (1) Does a surgeon's early THA cumulative percent revision (CPR) rate and (2) early TKA CPR rate correlate with the postoperative PROMs of patients undergoing primary THA and TKA, respectively, who have not undergone revision? METHODS: Elective primary THA and TKA procedures in patients with a primary diagnosis of osteoarthritis that were performed between August 2018 and December 2020 and registered in the Australian Orthopaedic Association National Joint Replacement Registry PROMs program were eligible. THAs and TKAs were eligible for inclusion in the primary analysis if 6-month postoperative PROMs were available, the operating surgeon was clearly identified, and the surgeon had performed at least 50 primary THAs or TKAs. Based on the inclusion criteria, 17,668 THAs were performed at eligible sites. We excluded 8878 procedures that were not matched to the PROMs program, leaving 8790 procedures. A further 790 were excluded because they were performed by unknown or ineligible surgeons or were revised, leaving 8000 procedures performed by 235 eligible surgeons, including 4256 (53%; 3744 cases of missing data) patients who had postoperative Oxford Hip Scores and 4242 (53%; 3758 cases of missing data) patients who had a postoperative EQ-VAS score recorded. Complete covariate data were available for 3939 procedures for the Oxford Hip Score and for 3941 procedures for the EQ-VAS. A total of 26,624 TKAs were performed at eligible sites. We excluded 12,685 procedures that were not matched to the PROMs program, leaving 13,939 procedures. A further 920 were excluded because they were performed by unknown or ineligible surgeons, or because they were revisions, leaving 13,019 procedures performed by 276 eligible surgeons, including 6730 (52%; 6289 cases of missing data) patients who had had postoperative Oxford Knee Scores and 6728 (52%; 6291 cases of missing data) patients who had a postoperative EQ-VAS score recorded. Complete covariate data were available for 6228 procedures for the Oxford Knee Score and for 6241 procedures for the EQ-VAS. The Spearman correlation between the operating surgeon's 2-year CPR and 6-month postoperative EQ-VAS Health and Oxford Hip or Oxford Knee Score was evaluated for THA and TKA procedures where a revision had not been performed. Associations between postoperative Oxford and EQ-VAS scores and a surgeon's 2-year CPR were estimated based on multivariate Tobit regressions and a cumulative link model with a probit link, adjusting for patient age, gender, ASA score, BMI category, preoperative PROMs, as well as surgical approach for THA. Missing data were accounted for using multiple imputation, with models assuming they were missing at random and a worst-case scenario. RESULTS: Of the eligible THA procedures, postoperative Oxford Hip Score and surgeon 2-year CPR were correlated so weakly as to be clinically irrelevant (Spearman correlation ρ = -0.09; p < 0.001), and the correlation with postoperative EQ-VAS was close to zero (ρ = -0.02; p = 0.25). Of the eligible TKA procedures, postoperative Oxford Knee Score and EQ-VAS and surgeon 2-year CPR were correlated so weakly as to be clinically irrelevant (ρ = -0.04; p = 0.004 and ρ = 0.03; p = 0.006, respectively). All models accounting for missing data found the same result. CONCLUSION: A surgeon's 2-year CPR did not exhibit a clinically relevant correlation with PROMs after THA or TKA, and all surgeons had similar postoperative Oxford scores. PROMs, revision rates, or both may be inaccurate or imperfect indicators of successful arthroplasty. Missing data may limit the findings of this study, although the results were consistent under a variety of different missing data scenarios. Innumerable factors contribute to arthroplasty results, including patient-related variables, differences in implant design, and the technical quality of the procedure. PROMs and revision rates may be analyzing two different facets of function after arthroplasty. Although surgeon variables are associated with revision rates, patient factors may exert a stronger influence on functional outcomes. Future research should identify variables that correlate with functional outcome. Additionally, given the gross level of function that Oxford scores record, outcome measures that can identify clinically meaningful functional differences are required. The use of Oxford scores in national arthroplasty registries may rightfully be questioned. LEVEL OF EVIDENCE: Level III, therapeutic study.

Is Enoxaparin Associated With a Higher Risk of Persistent Wound Drainage Than Aspirin? A Secondary Analysis of Data From the CRISTAL Randomized Trial.

BACKGROUND: Owing to its association with prosthetic joint infection, persistent wound drainage has become an important clinical entity after THA or TKA. The association between venous thromboembolism (VTE) prophylaxis and persistent wound drainage has not been extensively reported before but has potentially important clinical implications. QUESTIONS/PURPOSES: (1) Is the type of VTE prophylaxis (enoxaparin or aspirin) used after hip arthroplasty or knee arthroplasty associated with a higher risk of persistent wound drainage? (2) In patients who experience persistent wound drainage, is the type of VTE prophylaxis associated with a longer time taken to achieve a dry wound? (3) Is type of VTE prophylaxis associated with a higher risk of joint-related reoperation within 6 months? METHODS: This was a secondary analysis of data from an earlier cluster-randomized trial conducted through the Australian Orthopaedic Association National Joint Replacement Registry; data were drawn from two participating hospitals from that study. According to the trial's allocation sequence, the two participating hospitals were randomized to administer aspirin (100 mg daily) or enoxaparin (40 mg daily) as VTE prophylaxis to all patients undergoing hip arthroplasty for 35 days after the procedure and for all patients undergoing knee arthroplasty for 14 days afterwards. Crossover to the alternate prophylaxis group occurred after the patient enrollment target had been met for the first arm. Between April 2019 and December 2020, 1339 of 1679 eligible patients were included in this study; 82% (707 of 861) of eligible patients were allocated to the enoxaparin group and 77% (632 of 818) of eligible patients we allocated to the aspirin group. The mean age in both groups was 67 ± 10 years and the mean BMI was 32 ± 7 kg/m 2 . There was a higher proportion of male patients (43% [302 of 707] versus 36% [227 of 632]; p = 0.01), hip arthroplasties (36% [254 of 707] versus 29% [182 of 632]; p = 0.006), and patients receiving subcuticular closure (62% [441 of 707] versus 33% [208 of 631]; p < 0.001) in the enoxaparin group than in the aspirin group. Patients were monitored for wound drainage on each postoperative day until discharge, and this was recorded in the medical record once per day. Assessors were not blinded to the type of prophylaxis each patient received. Persistent wound drainage was defined as any wound drainage beyond Postoperative Day 3. For patients who experienced persistent wound drainage, the time taken to achieve a dry wound was defined as the number of days beyond Postoperative Day 3 for the wound to become dry. Logistic regression was used to determine whether the prophylaxis type was associated with persistent wound drainage. For patients with persistent wound drainage, the median time of drainage was compared between groups using the Kruskal-Wallis test. The number of patients undergoing a joint-related reoperation within 6 months was identified through data linkage to the Australian Orthopaedic Association National Joint Replacement Registry and electronic record review, and was compared using a Fisher exact test. RESULTS: We found no difference between the enoxaparin and aspirin groups in terms of the percentage of patients who had persistent wound drainage (9% [65 of 707] versus 8% [49 of 632], odds ratio 1.2 [95% confidence interval 0.8 to 1.8]; p = 0.40). For patients receiving subcuticular closure, after controlling for other potentially confounding variables, including age, sex, BMI, preoperative anticoagulant use, and type of arthroplasty, enoxaparin was associated with a higher risk of persistent wound drainage than aspirin (OR 3.6 [95% CI 1.5 to 10.6]; p = 0.009). For patients receiving a skin staple closure, after controlling for the same variables above, we found enoxaparin was not associated with a higher risk of persistent wound drainage (OR 1.1 [95% CI 0.7 to 1.9]; p = 0.66). For patients who experienced persistent wound drainage patients (114: 65 in the enoxaparin group and 49 in the aspirin group), there was no difference in the median (interquartile range) time taken to achieve a dry wound (enoxaparin: 1 day [IQR 1 to 2 days], aspirin: 1 day [IQR 1 to 3 days]; p = 0.22). There was no difference in the risk of joint-related reoperation within 6 months between enoxaparin (2.4% [17 of 707]) and aspirin (2.2% [14 of 632], OR 1.1 [95% CI 0.5 to 2.4]; p = 0.86). CONCLUSION: Enoxaparin was not associated with an increased risk of persistent wound drainage compared with aspirin for all patients included in this study. Enoxaparin may be associated with a higher risk of drainage for patients receiving subcuticular closure. However, this finding should be interpreted cautiously, given the small sample size in this analysis. The duration of drainage was short regardless of the prophylaxis used, and enoxaparin was not associated with an increased risk of joint-related reoperation. These findings should not deter clinicians from using enoxaparin for VTE prophylaxis after hip or knee arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

Discharge to inpatient rehabilitation following arthroplasty is a strong predictor of persistent opioid use 90 days after surgery: a prospective, observational study.

BACKGROUND: Total knee and hip arthroplasty are considered a clinically and cost-effective intervention, however, persistent pain post-surgery can occur, and some continue to take opioid medications long-term. One factor which has infrequently been included in prediction modelling is rehabilitation pathway, in particular, one which includes inpatient rehabilitation. As discharge to inpatient rehabilitation post-arthroplasty is common practice, we aimed to identify whether rehabilitation pathway (discharge to in-patient rehabilitation or not) predicts continued use of opioids at 3 months (90 days) post- total knee arthroplasty (TKA) and total hip arthroplasty (THA) whilst controlling for other covariates. METHODS: The study was nested within a prospective observational study capturing pre-operative, acute care and longer-term data from 1900 osteoarthritis (OA) patients who underwent primary TKA or THA. The larger study involved a part-random, part-convenience sample of 19 high-volume hospitals across Australia. Records with complete pre-and post-operative analgesic (35 days and 90 days) use were identified [1771 records (93% of sample)] and included in logistic regression analyses. RESULTS: Three hundred and thirteen people (17.8%) reported ongoing opioid use at 90 days post-operatively. In the adjusted model, admission to inpatient rehabilitation after surgery was identified as an independent and significant predictor of opioid use at 90-days. Inpatient rehabilitation was associated with almost twice the odds of persistent opioid use at 90-days compared to discharge directly home (OR = 1.9 (1.4, 2.5), p < .001). CONCLUSION: The inpatient rehabilitation pathway is a strong predictor of longer-term opioid use (90 days) post-arthroplasty, accounting for many known and possible confounders of use including sex, age, insurance status, major complications, smoking status and baseline body pain levels. TRIAL REGISTRATION: The study was nested within a prospective cohort observational study capturing pre-operative, acute-care and longer-term data from patients undergoing primary TKA or THA for osteoarthritis (ClinicalTrials.gov NCT01899443).

Comparative effectiveness of aspirin for symptomatic venous thromboembolism prophylaxis in patients undergoing total joint arthroplasty, a cohort study.

BACKGROUND: This study compares the symptomatic 90-day venous thromboembolism (VTE) rates in patients receiving aspirin to patients receiving low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), after total hip (THA) and total knee arthroplasty (TKA). METHODS: Data were collected from a multi-centre cohort study, including demographics, confounders and prophylaxis type (aspirin alone, LMWH alone, aspirin and LMWH, and DOACs). The primary outcome was symptomatic 90-day VTE. Secondary outcomes were major bleeding, joint related reoperation and mortality within 90 days. Data were analysed using logistic regression, the Student's t and Fisher's exact tests (unadjusted) and multivariable regression (adjusted). RESULTS: There were 1867 eligible patients; 365 (20%) received aspirin alone, 762 (41%) LMWH alone, 482 (26%) LMWH and aspirin and 170 (9%) DOAC. The 90-day VTE rate was 2.7%; lowest in the aspirin group (1.6%), compared to 3.6% for LMWH, 2.3% for LMWH and aspirin and 2.4% for DOACs. After adjusted analysis, predictors of VTE were prophylaxis duration < 14 days (OR = 6.7, 95% CI 3.5-13.1, p < 0.001) and history of previous VTE (OR = 2.4, 95% CI 1.1-5.8, p = 0.05). There were no significant differences in the primary or secondary outcomes between prophylaxis groups. CONCLUSIONS: Aspirin may be suitable for VTE prophylaxis following THA and TKA. The comparatively low unadjusted 90-day VTE rate in the aspirin group may have been due to selective use in lower-risk patients. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov, trial number NCT01899443 (15/07/2013).

Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain : A Systematic Review and Meta-analysis.

BACKGROUND: The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain. PURPOSE: To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting. DATA SOURCES: Electronic databases and registries from inception to 7 February 2022. STUDY SELECTION: Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED. DATA EXTRACTION: Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. DATA SYNTHESIS: Forty-two articles were included (n = 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics. LIMITATIONS: Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes. CONCLUSION: The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42021275293).

Six hundred years of South American tree rings reveal an increase in severe hydroclimatic events since mid-20th century.

South American (SA) societies are highly vulnerable to droughts and pluvials, but lack of long-term climate observations severely limits our understanding of the global processes driving climatic variability in the region. The number and quality of SA climate-sensitive tree ring chronologies have significantly increased in recent decades, now providing a robust network of 286 records for characterizing hydroclimate variability since 1400 CE. We combine this network with a self-calibrated Palmer Drought Severity Index (scPDSI) dataset to derive the South American Drought Atlas (SADA) over the continent south of 12°S. The gridded annual reconstruction of austral summer scPDSI is the most spatially complete estimate of SA hydroclimate to date, and well matches past historical dry/wet events. Relating the SADA to the Australia-New Zealand Drought Atlas, sea surface temperatures and atmospheric pressure fields, we determine that the El Niño-Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) are strongly associated with spatially extended droughts and pluvials over the SADA domain during the past several centuries. SADA also exhibits more extended severe droughts and extreme pluvials since the mid-20th century. Extensive droughts are consistent with the observed 20th-century trend toward positive SAM anomalies concomitant with the weakening of midlatitude Westerlies, while low-level moisture transport intensified by global warming has favored extreme rainfall across the subtropics. The SADA thus provides a long-term context for observed hydroclimatic changes and for 21st-century Intergovernmental Panel on Climate Change (IPCC) projections that suggest SA will experience more frequent/severe droughts and rainfall events as a consequence of increasing greenhouse gas emissions.

Does Radiographic Alignment Correlate With Patient-Reported Functional Outcomes and Posttreatment Complications in Older Patients Treated for Wrist Fractures?

PURPOSE: Surgical treatment of distal radius fractures provides better fracture alignment than closed reduction; however, surgical treatment does not lead to better patient-reported function at 12 months. The aims of this study were to report the radiographic outcomes from the Combined Randomized and Observational Study of Surgery for Fractures In the distal Radius in the Elderly trial, investigate the association between radiographic outcomes and patient-reported function, and explore whether this association was affected by posttreatment complications and direction of malalignment. METHODS: This study used the outcomes of the Combined Randomized and Observational Study of Surgery for Fractures In the distal Radius in the Elderly trial, which is a combined randomized and observational trial that compared volar-locking plate fixation with closed reduction and cast immobilization, to treat distal radius fractures in patients aged ≥60 years. Four radiographic outcomes (dorsal angulation, radial inclination, ulnar variance, and articular step) were reported at the following three time frames: (1) baseline, (2) after treatment, and (3) ≥6 weeks by treatment group. Secondary analysis was correlation of 12-month patient-reported function scores with 6-week radiographic measures for each of four radiographic parameters, and a subgroup analysis was conducted to investigate if this was affected by posttreatment complications. Tertiary analysis investigated if direction of malalignment affected the secondary analysis. RESULTS: We recruited 300 participants (166 randomized and 134 observational); 113 had volar-locking plate fixation, and 187 had closed reduction. There were no between-group differences for each of the four pretreatment radiographic parameters, but there were between-treatment group differences for all four radiographic parameters apart from articular step. We found no association between patient-reported function at 12 months and each of the four radiographic parameters at 6 weeks. This lack of association was unaffected by posttreatment complications and the direction of malalignment. CONCLUSIONS: For patients with wrist fractures aged ≥60 years, final radiographic alignment did not correlate with patient-reported function at 12 months. These findings were not affected by treatment type, and there was no association between radiographic alignment and posttreatment complications. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.