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.

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.

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.

Maternal and early life nutrition and physical activity: setting the research and intervention agenda for addressing the double burden of malnutrition in South African children.

Early life is important for later health outcomes, yet there are few studies which adequately address all of the potential early life insults that may affect later life health and growth trajectories. This is particularly evident in low- to middle-income countries such as South Africa, where women of childbearing age are particularly vulnerable to high levels of physical inactivity, malnutrition, and obesity. Pregnancy may therefore be an opportune time to change behaviours and improve maternal and offspring health outcomes, and decrease the inter-generational transfer of risk. We show clear evidence that physical activity and nutrition are important target areas for intervention during pregnancy and in the early years of life, yet that current literature in Africa, and specifically South Africa, is limited. We have outlined the available literature concerning the impact of maternal and early life nutrition and physical activity on the health status of South African children, and have provided some recommendations for future research and policy.

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.

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.

Temporal changes in hematologic markers after splenectomy, splenic embolization, and observation for trauma.

INTRODUCTION: The spleen is one of the most commonly injured abdominal solid organs during blunt trauma. Modern management of splenic trauma has evolved to include non-operative therapies, including observation and angioembolization to preclude splenectomy in most cases of blunt splenic injury. Despite the shift in management strategies, relatively little is known about the hematologic changes associated with these various modalities. The aim of this study was to determine if there are significant differences in hematologic characteristics over time based on the treatment modality employed following splenic trauma. We hypothesized that alterations seen in hematologic parameters would vary between observation (OBS), embolization (EMB), and splenectomy (SPL) in the setting of splenic injury. METHODS: An institutional review board-approved, retrospective study of routine hematologic indices examined data between March 2000 and December 2014 at three academic trauma centers. A convenience sample of patients with splenic trauma and admission lengths of stay >96 h was selected for inclusion, resulting in a representative sample of each sub-group (OBS, EMB, and SPL). Basic demographics and injury severity data (ISS) were abstracted. Platelet count, red blood cell (RBC) count and RBC indices, and white blood cell (WBC) count with differential were analyzed between the time of admission and a maximum of 1080 h (45 days) post-injury. Comparisons between OBS, EMB, and SPL groups were then performed using non-parametric statistical testing, with statistical significance set at p < 0.05. RESULTS: Data from 130 patients (40 SPL, 40 EMB, and 50 OBS) were analyzed. The median age was 40 years, with 67 % males. Median ISS was 21.5 (21 for SPL, 19 for EMB, and 22 for OBS, p = n/s) and median Glasgow Coma Scale (GCS) was 15. Median splenic injury grade varied by interventional modality (grade 4 for SPL, 3 for EMB, and 2 for OBS, p < 0.05). Inter-group comparisons demonstrated no significant differences in RBC counts. However, mean corpuscular volume (MCV) and RBC distribution width (RDW) were elevated in the SPL and EMB groups (p < 0.01). Similarly, EMB and SPL groups had higher platelet counts than the OBS group (p < 0.01). In aggregate, WBC counts were highest following SPL, followed by EMB and OBS (p < 0.01). Similar trends were noted in neutrophil and monocyte counts (p < 0.01), but not in lymphocyte counts (p = n/s). CONCLUSION: This study describes important trends and patterns among fundamental hematologic parameters following traumatic splenic injuries managed with SPL, EMB, or OBS. As expected, observed WBC counts were highest following SPL, then EMB, and finally OBS. No differences were noted in RBC count between the three groups, but RDW was significantly greater following SPL compared to EMB and OBS. We also found that MCV was highest following OBS, when compared to EMB or SPL. Finally, our data indicate that platelet counts are similarly elevated for both SPL and EMB, when compared to the OBS group. These results provide an important foundation for further research in this still relatively unexplored area.

La aplicación efectiva de la investigación usando métodos mixtos / The effective application of mixed-methods research / A aplicação efetiva da pesquisa usando métodos mistos

En respuesta a las cada vez mayores disparidades en salud alrededor del mundo, los científicos han identificado métodos de investigación alternativos que se establecen para mejorar la salud de las poblaciones sub-atendidas. Un acercamiento bien conocido es el de los métodos-mixtos, el cual implica la obtención y el análisis de datos tanto cuantitativos como cualitativos para entender un problema de investigación 1 . No obstante, que la investigación que usa métodos mixtos pudiera parecer fácil de implementar, los científicos necesitan considerar las siguientes cuestiones antes de desarrollar un estudio aplicando un diseño con métodos mixtos: 1) ¿Son las preguntas de investigación apropiadas para un estudio con métodos mixtos?, 2) ¿Cómo pueden los científicos diseñar estudios con métodos mixtos combinando métodos tanto cuantitativos como cualitativos para lograr los resultados más efectivos? y 3) ¿Cuáles son las mejores posiciones filosóficas y teóricas que los científicos pueden usar para enmarcar un estudio con métodos mixtos? Las respuestas a estas preguntas pueden ayudar a los científicos a desarrollar e implementar de forma rigurosa estudios con métodos mixto

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.

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.

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.

Animal models of cartilage repair.

Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the 'holy grail' of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89-94.

Nasoenteric tube complications.

The use of nasoenteric tubes (NETs) is ubiquitous, and clinicians often take their placement, function, and maintenance for granted. NETs are used for gastrointestinal decompression, enteral feeding, medication administration, naso-biliary drainage, and specialized indications such as upper gastrointestinal bleeding. Morbidity associated with NETs is common, but frequently subtle, mandating high index of suspicion, clinical vigilance, and patient safety protocols. Common complications include sinusitis, sore throat and epistaxis. More serious complications include luminal perforation, pulmonary injury, aspiration, and intracranial placement. Frequent monitoring and continual re-review of the indications for continued use of any NET is prudent, including consideration of changing goals of care. This manuscript reviews NET-related complications and associated topics.

The potential impact of a cataract surgery programme on the care of orphans and vulnerable children in Swaziland.

We aimed to evaluate the potential impact of a cataract surgery programme at the Good Shepherd Hospital, Siteki, Swaziland, on the care of orphans and vulnerable children in Swaziland. We studied consecutive patients aged 50 years and older undergoing surgery for age-related cataract who reported having children living in their household. Of 131 subjects recruited, 65 (49.6%) were the primary caregivers for the child(ren) in their household. Visual acuities measured 2 weeks after surgery significantly improved. Four weeks after surgery, there was a sizable increase in the proportions of subjects who were able to undertake self-care activities, attend to activities of daily living, undertake income-generating activities and care for children. Cataract surgery on elderly visually impaired patients has the potential to impact positively on the care of orphans and vulnerable children.

Synthesis and antihormonal properties of novel 11ß-benzoxazole-substituted steroids.

Early studies led to the identification of 11ß-aryl-4',5'-dihydrospiro[estra-4,9-diene-17ß,4'-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4'-dimethylaminophenyl group of mifepristone with the benzoxazol group to give 5a-d. We also prepared the 17ß-formamido analogs 6a,b using a new synthetic strategy via the intermediate epoxide 21. These compounds were evaluated for their antagonist hormonal properties using the T47D cell-based alkaline phosphatase assay and the A549 cell-based functional assay. Compound 5c showed potent antagonist activity at GR with better selectivity for GR versus PR than mifepristone and is a promising lead for further development.

Consumption of oxygen: a mitochondrial-generated progression signal of advanced cancer.

Changes in mitochondrial genome such as mutation, deletion and depletion are common in cancer and can determine advanced phenotype of cancer; however, detailed mechanisms have not been elucidated. We observed that loss of mitochondrial genome reversibly induced overexpression and activation of proto-oncogenic Ras, especially K-Ras 4A, responsible for the activation of AKT and ERK leading to advanced phenotype of prostate and breast cancer. Ras activation was induced by the overexpression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), the rate-limiting enzyme of the mevalonate pathway. Hypoxia is known to induce proteasomal degradation of HMGR. Well differentiated prostate and breast cancer cells with high mitochondrial DNA content consumed a large amount of oxygen and induced hypoxia. Loss of mitochondrial genome reduced oxygen consumption and increased in oxygen concentration in the cells. The hypoxic-to-normoxic shift led to the overexpression of HMGR through inhibiting proteasomal degradation. Therefore, reduction of mitochondrial genome content induced overexpression of HMGR through hypoxic to normoxic shift and subsequently the endogenous induction of the mevalonate pathway activated Ras that mediates advanced phenotype. Reduction of mitochondrial genome content was associated with the aggressive phenotype of prostate cancer in vitro cell line model and tissue specimens in vivo. Our results elucidate a coherent mechanism that directly links the mitochondrial genome with the advanced progression of the disease.