The buzz within: the role of the gut microbiome in honeybee social behavior.

Gut symbionts influence the physiology and behavior of their host, but the extent to which these effects scale to social behaviors is an emerging area of research. The use of the western honeybee (Apis mellifera) as a model enables researchers to investigate the gut microbiome and behavior at several levels of social organization. Insight into gut microbial effects at the societal level is critical for our understanding of how involved microbial symbionts are in host biology. In this Commentary, we discuss recent findings in honeybee gut microbiome research and synthesize these with knowledge of the physiology and behavior of other model organisms to hypothesize how host-microbe interactions at the individual level could shape societal dynamics and evolution.

The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Accuracy of Tongue Swab Testing Using Xpert MTB-RIF Ultra for Tuberculosis Diagnosis.

Tongue dorsum swabs have shown promise as alternatives to sputum for detecting Mycobacterium tuberculosis (MTB) in patients with pulmonary tuberculosis (TB). Some of the most encouraging results have come from studies that used manual quantitative PCR (qPCR) to analyze swabs. Studies using the automated Cepheid Xpert MTB/RIF Ultra qPCR test (Xpert Ultra) have exhibited less sensitivity with tongue swabs, possibly because Xpert Ultra is optimized for testing sputum, not tongue swab samples. Using two new sample preprocessing methods that demonstrated good sensitivity in preliminary experiments, we assessed diagnostic accuracy and semi-quantitative signals of Xpert Ultra performed on tongue swabs collected from 183 adults with presumed TB in Kampala, Uganda. Relative to a sputum Xpert Ultra reference standard, the sensitivity of tongue swab Xpert Ultra was 77.8% (95% confidence interval [CI] 64.4-88.0) and specificity was 100.0% (95% CI, 97.2-100.0). When compared to a microbiological reference standard (MRS) incorporating both sputum Xpert Ultra and sputum mycobacterial culture, sensitivity was 72.4% (95% CI, 59.1-83.3) and specificity remained the same. Semi-quantitative Xpert Ultra results were generally lower with tongue swabs than with sputum, and cycle threshold values were higher. None of the eight sputum Xpert Ultra "trace" or "very low" results were detected using tongue swabs. Tongue swabs should be considered when sputum cannot be collected for Xpert Ultra testing, or in certain mass-screening settings. Further optimization of tongue swab analysis is needed to achieve parity with sputum-based molecular testing for TB.

Multigenerational Effects of Early-Life Health Shocks.

A large literature has documented links between harmful early-life exposures and later-life health and socioeconomic deficits. These studies, however, have typically been unable to examine the possibility that these shocks are transmitted to the next generation. Our study uses representative survey data from the United States to trace the impacts of in utero exposure to the 1918 influenza pandemic on the outcomes of the children and grandchildren of those affected. We find evidence of multigenerational effects on educational, economic, and health outcomes.

Evaluating vaccination strategies to control foot-and-mouth disease: a country comparison study.

Vaccination is increasingly being recognised as a potential tool to supplement 'stamping out' for controlling foot-and-mouth disease (FMD) outbreaks in non-endemic countries. Infectious disease simulation models provide the opportunity to determine how vaccination might be used in the face of an FMD outbreak. Previously, consistent relative benefits of specific vaccination strategies across different FMD simulation modelling platforms have been demonstrated, using a UK FMD outbreak scenario. We extended this work to assess the relative effectiveness of selected vaccination strategies in five countries: Australia, New Zealand, the USA, the UK and Canada. A comparable, but not identical, FMD outbreak scenario was developed for each country with initial seeding of Pan Asia type O FMD virus into an area with a relatively high density of livestock farms. A series of vaccination strategies (in addition to stamping out (SO)) were selected to evaluate key areas of interest from a disease response perspective, including timing of vaccination, species considerations (e.g. vaccination of only those farms with cattle), risk area vaccination and resources available for vaccination. The study found that vaccination used with SO was effective in reducing epidemic size and duration in a severe outbreak situation. Early vaccination and unconstrained resources for vaccination consistently outperformed other strategies. Vaccination of only those farms with cattle produced comparable results, with some countries demonstrating that this could be as effective as all species vaccination. Restriction of vaccination to higher risk areas was less effective than other strategies. This study demonstrates consistency in the relative effectiveness of selected vaccination strategies under different outbreak start up conditions conditional on the assumption that each of the simulation models provide a realistic estimation of FMD virus spread. Preferred outbreak management approaches must however balance the principles identified in this study, working to clearly defined outbreak management objectives, while having a good understanding of logistic requirements and the socio-economic implications of different control measures.

Basal and stress-induced salivary testosterone variation across the menstrual cycle and linkage to motivation and muscle power.

This study investigated salivary testosterone (sal-T) variation across the menstrual cycle in female athletes, at different competitive levels, and its association with motivation and neuromuscular power. Six elite and 16 non-elite female athletes were monitored on days 7 (D7), 14 (D14), and 21 (D21) across 3 menstrual cycles for basal sal-T concentrations and self-appraised motivation to train and compete. Two further measures were taken on D7, D14, and D21 across 2 menstrual cycles: (1) the sal-T response (delta change) to a physical stress test and (2) peak power (PP) response to a 6-second cycle sprint following a post-activation potentiation (PAP) stimulus. Basal sal-T concentrations increased by 17 ± 27% from D7 to D14 before decreasing by -25 ± 43% on D21 (P < .05), but this result was biased by elite females with higher sal-T (>102%) who showed larger menstrual changes. Motivation, sal-T reactivity to stress, and the PP responses to a PAP stimulus also varied by testing day (P < .05), in parallel with basal sal-T and in favor of the elite group. Furthermore, stronger within-subject relationships (P < .001) between basal sal-T and motivation emerged in the elites (r = .70-.75) vs the non-elite group (r = .41-.50). In conclusion, menstrual cycle changes in sal-T were more obvious in high-performing female athletes with higher sal-T concentrations. This was accompanied by greater training motivation, a more pronounced sal-T response to a physical stressor and greater neuromuscular power in the elite group. These results support observations that female athletes with higher T are more represented at elite levels of performance.

Fat mass and obesity associated (FTO) gene influences skeletal muscle phenotypes in non-resistance trained males and elite rugby playing position.

BACKGROUND: FTO gene variants have been associated with obesity phenotypes in sedentary and obese populations, but rarely with skeletal muscle and elite athlete phenotypes. METHODS: In 1089 participants, comprising 530 elite rugby athletes and 559 non-athletes, DNA was collected and genotyped for the FTO rs9939609 variant using real-time PCR. In a subgroup of non-resistance trained individuals (NT; n = 120), we also assessed structural and functional skeletal muscle phenotypes using dual energy x-ray absorptiometry, ultrasound and isokinetic dynamometry. In a subgroup of rugby athletes (n = 77), we assessed muscle power during a countermovement jump. RESULTS: In NT, TT genotype and T allele carriers had greater total body (4.8% and 4.1%) and total appendicular lean mass (LM; 3.0% and 2.1%) compared to AA genotype, with greater arm LM (0.8%) in T allele carriers and leg LM (2.1%) for TT, compared to AA genotype. Furthermore, the T allele was more common (94%) in selected elite rugby union athletes (back three and centre players) who are most reliant on LM rather than total body mass for success, compared to other rugby athletes (82%; P = 0.01, OR = 3.34) and controls (84%; P = 0.03, OR = 2.88). Accordingly, these athletes had greater peak power relative to body mass than other rugby athletes (14%; P = 2 x 10-6). CONCLUSION: Collectively, these results suggest that the T allele is associated with increased LM and elite athletic success. This has implications for athletic populations, as well as conditions characterised by low LM such as sarcopenia and cachexia.

Important clinical descriptors to include in the examination and assessment of patients with femoroacetabular impingement syndrome: an international and multi-disciplinary Delphi survey.

PURPOSE: Determine which examination findings are key clinical descriptors of femoroacetabular impingement syndrome (FAIS) through use of an international, multi-disciplinary expert panel. METHODS: A three-round Delphi survey utilizing an international, multi-disciplinary expert panel operationally defined from international publications and presentations was utilized. RESULTS: All six domains (subjective examination, patient-reported outcome measures, physical examination, special tests, physical performance measures, and diagnostic imaging) had at least one descriptor with 75% consensus agreement for diagnosis and assessment of FAIS. Diagnostic imaging was the domain with the highest level of agreement. Domains such as patient-reported outcome measures (PRO's) and physical examination were identified as non-diagnostic measures (rather as assessments of disease impact). CONCLUSION: Although it also had the greatest level of variability in description of examination domains, diagnostic imaging continues to be the preeminent diagnostic measure for FAIS. No single domain should be utilized as the sole diagnostic or assessment parameter for FAIS. While not all investigated domains provide diagnostic capability for FAIS, those that do not are able to serve purpose as a measure of disease impact (e.g., impairments and activity limitations). The clinical relevance of this Delphi survey is the understanding that a comprehensive assessment measuring both diagnostic capability and disease impact most accurately reflects the patient with FAIS. LEVEL OF EVIDENCE: V.

Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position.

We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ(2) and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ(2) = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ(2) = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics.

Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.

Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p < 0.001). Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes.

Temporal associations between individual changes in hormones, training motivation and physical performance in elite and non-elite trained men.

To advance our understanding of the hormonal contribution to athletic performance, we examined the temporal associations between individual changes in testosterone (T) and/or cortisol (C) concentrations, training motivation and physical performance in elite and non-elite trained men. Two male cohorts classified as elites (n = 12) and non-elites (n = 12) completed five testing sessions over a six-week period. The athletes were tested for salivary T, C, T/C ratio, self-perceived training motivation, countermovement jump (CMJ) height and isometric mid-thigh pull peak force (IMTP PF), after which an actual training workout was performed. The elite men reported higher motivation to train and they produced greater CMJ height overall, whereas the non-elites had higher pooled T levels (p < 0.05). No significant group differences in C concentrations, T/C ratio or IMTP PF were found. The individual changes in T levels were positively associated with training motivation in the elite men only (p = 0.033), but the hormonal and motivation measures did not predict CMJ height or IMTP PF in either group. The monitoring of elite and non-elite men across a short training block revealed differences in T levels, motivation and lower-body power, which may reflect training and competitive factors in each group. Despite having lower T levels, the elite athletes showed better linkage between pre-training T fluctuations and subsequent motivation to train. The nature of the performance tests (i.e. single repetition trials) could partly explain the lack of an association with the hormonal and motivational measures.

Evaluating vaccination strategies to control foot-and-mouth disease: a model comparison study.

Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

Diagnostic accuracy of clinical tests for the diagnosis of hip femoroacetabular impingement/labral tear: a systematic review with meta-analysis.

BACKGROUND: Surgery for hip femoroacetabular impingement/acetabular labral tear (FAI/ALT) is exponentially increasing despite lacking investigation of the accuracy of various diagnostic measures. Useful clinical utility of these measures is necessary to support diagnostic imaging and subsequent surgical decision-making. OBJECTIVE: Summarise/evaluate the current diagnostic accuracy of various clinical tests germane to hip FAI/ALT pathology. METHODS: A computer-assisted literature search of MEDLINE, CINAHL and EMBASE databases using keywords related to diagnostic accuracy of the hip joint, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the search and reporting phases of the study. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies-2 (QUADAS-2). Random effects models were used to summarise sensitivities (SN), specificities (SP), diagnostic odds ratio (DOR) and respective confidence intervals (CI). RESULTS: The employed search strategy revealed 21 potential articles, with one demonstrating high quality. Nine articles qualified for meta-analysis. The meta-analysis demonstrated that flexion-adduction-internal rotation (pooled SN ranging from 0.94 (95% CI 0.90 to 0.97) to 0.99 (95% CI 0.98 to 1.00); DOR 5.71 (95% CI 0.84 to 38.86) to 7.82 (95% CI 1.06 to 57.84)) and flexion-internal rotation (pooled SN 0.96 (95% CI 0.81 to 0.99); DOR 8.36 (95% CI 0.41 to 171.3) tests possess only screening accuracy. CONCLUSIONS: Few hip physical examination tests for diagnosing FAI/ALT have been investigated in enough studies of substantial quality to direct clinical decision-making. Further high-quality studies across a wider spectrum of hip pathology patients are recommended to discern the confirmed clinical utility of these tests. TRIALS REGISTRATION NUMBER: PROSPERO Registration # CRD42014010144.

Are we missing the boat? Current uses of long-term biological monitoring data in the evaluation and management of marine protected areas.

Protected area management agencies are increasingly using management effectiveness evaluation (MEE) to better understand, learn from and improve conservation efforts around the globe. Outcome assessment is the final stage of MEE, where conservation outcomes are measured to determine whether management objectives are being achieved. When quantitative monitoring data are available, best-practice examples of outcome assessments demonstrate that data should be assessed against quantitative condition categories. Such assessments enable more transparent and repeatable integration of monitoring data into MEE, which can promote evidence-based management and improve public accountability and reporting. We interviewed key informants from marine protected area (MPA) management agencies to investigate how scientific data sources, especially long-term biological monitoring data, are currently informing conservation management. Our study revealed that even when long-term monitoring results are available, management agencies are not using them for quantitative condition assessment in MEE. Instead, many agencies conduct qualitative condition assessments, where monitoring results are interpreted using expert judgment only. Whilst we found substantial evidence for the use of long-term monitoring data in the evidence-based management of MPAs, MEE is rarely the sole mechanism that facilitates the knowledge transfer of scientific evidence to management action. This suggests that the first goal of MEE (to enable environmental accountability and reporting) is being achieved, but the second and arguably more important goal of facilitating evidence-based management is not. Given that many MEE approaches are in their infancy, recommendations are made to assist management agencies realize the full potential of long-term quantitative monitoring data for protected area evaluation and evidence-based management.

Acute appendicitis in South Africa: a systematic review.

BACKGROUND: Acute appendicitis is one of the most common surgical emergencies in the West. A large body of research is investigating the risk factors for disease and perforation. As South Africa has a social environment, health system structure, and population demography unique from developed nations, the findings may not be generalisable to this setting. A systematic review has not been performed for appendicitis research in South Africa. The objective of this review was to systematically examine the literature on appendicitis in South Africa. METHOD: Published articles discussing appendicitis in South Africa up to March 2014 were identified using MEDLINE and EBMReviews. Research themes were analysed in the literature. Perforation rates, mortality, negative appendicectomy rates and gender differences were analysed from audits of patients undergoing appendicectomy for acute appendicitis. RESULTS: Ten audits were included in the quantitative analysis. Some were excluded in the subgroup analyses. Negative appendicectomies occurred at a rate of 17% (580/3 354). Women were more likely to have a negative appendicectomy than men (28% vs. 9%, p < 0.01). The perforation rate for appendicectomy patients was 36% (970/2 688), and mortality rate was 1% (36/2 946). Research efforts focused on investigating differential incidence and outcomes between racial groups within the country. CONCLUSION: Appendicitis trends in South Africa are consistent with those in developing regions. However, there is lack of research from the private sector. Further research is needed to investigate specific factors which delay care, outcomes and cost analyses for laparoscopic surgery, and the system strengthening of surgical services at district hospitals.

Trained and untrained males show reliable salivary testosterone responses to a physical stimulus, but not a psychological stimulus.

BACKGROUND: The testosterone (T) responses to a physical stimulus are thought to be more stable and reproducible compared to a psychological stimulus. PURPOSE: This study compared the salivary T (Sal-T) responses to both stimuli in four groups of men: professional rugby players (n = 17), recreational rugby players (n = 10), a mixed athlete group (n = 14) and untrained controls (n = 12). METHODS: Each group completed three treatments: (1) watching a video with aggressive rugby footage, (2) performing a short bout of sprint exercise and (3) a control session. Saliva samples were taken before and 15 min after each treatment. RESULTS: The sprint exercise changes in Sal-T levels were similar in the elite rugby (17.1 ± 11.1%), recreational rugby (11.9 ± 15.9%), mixed athlete (27.6 ± 32.0%) and control groups (25.3 ± 23.6%). In response to the video, Sal-T increased in the elite rugby (6.9 ± 6.4%) and untrained groups (11.9 ± 13.5%), but decreased in the recreational rugby players (-7.5 ± 11.0%). The individual Sal-T responses to the sprints were also correlated (r = 0.69 to 0.82) with other treatment responses. CONCLUSIONS: Sprint exercise had a more consistent effect on Sal-T than a video with aggressive content and thus, could provide a reliable stimulus for increasing T availability in men with different training backgrounds. Individual Sal-T reactivity also appears to be somewhat stable across different treatments. These data provide further understanding around the induction, moderation and interpretation of T physiology.

Pre-injury neuro-psychiatric medication use, alone or in combination with cardiac medications, may affect outcomes in trauma patients.

BACKGROUND: Recent review of older (≥45-years-old) patients admitted to our trauma center showed that more than one-third were using neuro-psychiatric medications (NPMs) prior to their injury-related admission. Previously published data suggests that use of NPMs may increase patients' risk and severity of injury. We sought to examine the impact of pre-injury NPM use on older trauma patients' morbidity and mortality. MATERIALS AND METHODS: Retrospective record review included medication regimen characteristics and NPM use (antidepressants-AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day survival were examined. Comparisons included regimens involving NPMs, further focusing on their interactions with various cardiac medications (beta blocker - BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker - ACE/ARB; calcium channel blocker - CCB). RESULTS: 712 patient records were reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect of NPM monotherapy on hospital mortality. Patients taking ≥3 NPMs had significantly lower 90-day survival compared to patients taking ≤2 NPMs (81% for 3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac medication (CM) combinations were associated with increased mortality compared to monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs 4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). CONCLUSIONS: Large proportion of older trauma patients was using pre-injury NPMs. Several regimens involving NPMs and CMs were associated with increased in-hospital mortality. Additionally, use of ≥3 NPMs was associated with lower 90-day survival.

"Fight-bite": not just a hand problem.

Human bite wounds around the knee are rarely seen, yet may require the same urgent attention as a fight bite to the hand. Two cases of polymicrobial septic arthritis of the knee secondary to a human bite wound are described. In both the cases, the diagnosis of the septic arthritis was delayed because the intra-articular wound was unrecognized. The injuries were initially deemed superficial and managed with local wound care. In each case, the knee was flexed at the time of injury and the quadriceps tendon was penetrated by a tooth which inoculated the knee joint. Septic arthritis of the knee presented, in both cases, 72 hours after the injury. These infections proved challenging to treat and required multiple surgeries and prolonged antibiotic therapy. The "fight bite" phenomenon of the hand is widely recognized and the same phenomenon can occur at the knee.

How long does tendinopathy last if left untreated? Natural history of the main tendinopathies affecting the upper and lower limb: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Natural history of disease refers to the progression of a disease process in an individual over time, in the absence of treatment. Understanding natural history of tendinopathies is key for clinicians to make accurate prognostic predictions and design effective intervention studies. OBJECTIVE: To quantify the natural history of the main tendinopathies regarding pain and function and to compare outcomes between untreated individuals and those receiving treatment. METHODS: A systematic literature search was conducted until February 2023, across PubMed, Cochrane, Embase and Scopus databases. Selection criteria included randomized controlled trials (RCTs) with a "wait-and-see" group and cohort studies with ≥3 months of follow-up reporting on pain and function-related outcomes. Standardized mean differences (SMDs) of "wait-and-see" groups were pooled using a random-effects inverse-variance model. Risk of bias was assessed using Cochrane Risk-of-Bias (RoB2), and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Six RCTs were included, encompassing 518 subjects with tendinopathy. Pooled results demonstrated significant pain (SMD = 0.30, 95%CI: 0.19-0.41) and physical function improvement (SMD = 0.38, 95%CI: 0.28-0.48). These estimates remained consistent regardless of age or follow-up duration. In rotator cuff tendinopathy, untreated individuals improved but did not fully recover at one year, with similar outcomes to other interventions (e.g., surgery). Subjects with lateral elbow, patellar and achilles tendinopathies when untreated, did not fully resolve symptoms within 12-16 weeks. CONCLUSIONS: This review provides limited conclusions about natural history of tendinopathies. Future studies should incorporate true no-intervention groups to accurately reflect tendinopathy's natural progression.