HPV infection and number of lifetime sexual partners are strong predictors for ‘natural’ regression of CIN 2 and 3

The aim of this paper was to evaluate the factors that predict regression of untreated CIN 2 and 3. A total of 93 patients with colposcopic persistent CIN 2 and 3 lesions after biopsy were followed for 6 months. Human papillomavirus (HPV) types were determined by polymerase chain reaction at enrolment. We analysed the biologic and demographic predictors of natural regression using univariate and multivariate methods. The overall regression rate was 52% (48 out of 93), including 58% (22 out of 38) of CIN 2 and 47% (26 out of 55) of CIN 3 lesions (P=0.31 for difference). Human papillomavirus was detected in 84% (78 out of 93) of patients. In univariate analysis, 80% (12 out of 15) of lesions without HPV regressed compared to 46% (36 out of 78) of lesions with HPV infection (P=0.016). Women without HPV and those who had a resolution of HPV had a four-fold higher chance of regression than those with persistent HPV (relative odds=3.5, 95% CI=1.4-8.6). Women with five or fewer lifetime sexual partners had higher rates of regression than women with more than five partners (P=0.003). In multivariate analysis, HPV status and number of sexual partners remained as significant independent predictors of regression. In conclusion, HPV status and number of lifetime sexual partners were strongly predictive of regression of untreated CIN 2 and 3

Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer

The folate derivatives folic acid (FA) and folinic acid (FNA) decrease the in vivo and in vitro activities of antifolate drugs in Plasmodium falciparum. However, the effects of 5-methyl-tetrahydrofolate (5-Me-THF) and tetrahydrofolate (THF), the two dominant circulating folate forms in humans, have not been explored yet. We have investigated the effects of FA, FNA, 5-Me-THF, and THF on the in vitro activity of the antimalarial antifolates pyrimethamine and chlorcycloguanil and the anticancer antifolates methotrexate (MTX), aminopterin, and trimetrexate (TMX), against P. falciparum. The results indicate that these anticancers are potent against P. falciparum, with IC50 < 50 nM. 5-Me-THF does not significantly decrease the activity of all tested drugs, and none of the tested folate derivatives significantly decrease the activity of these anticancers. Thus, malaria folate metabolism has features different from those in human, and the exploitation of this difference could lead to the discovery of new drugs to treat malaria. For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria

A prospective study of shoulder pain in primary care: Prevalence of imaged pathology and response to guided diagnostic blocks

<p>Abstract</p> <p>Background</p> <p>The prevalence of imaged pathology in primary care has received little attention and the relevance of identified pathology to symptoms remains unclear. This paper reports the prevalence of imaged pathology and the association between pathology and response to diagnostic blocks into the subacromial bursa (SAB), acromioclavicular joint (ACJ) and glenohumeral joint (GHJ).</p> <p>Methods</p> <p>Consecutive patients with shoulder pain recruited from primary care underwent standardised x-ray, diagnostic ultrasound scan and diagnostic injections of local anaesthetic into the SAB and ACJ. Subjects who reported less than 80% reduction in pain following either of these injections were referred for a magnetic resonance arthrogram (MRA) and GHJ diagnostic block. Differences in proportions of positive and negative imaging findings in the anaesthetic response groups were assessed using Fishers test and odds ratios were calculated a for positive anaesthetic response (PAR) to diagnostic blocks.</p> <p>Results</p> <p>In the 208 subjects recruited, the rotator cuff and SAB displayed the highest prevalence of pathology on both ultrasound (50% and 31% respectively) and MRA (65% and 76% respectively). The prevalence of PAR following SAB injection was 34% and ACJ injection 14%. Of the 59% reporting a negative anaesthetic response (NAR) for both of these injections, 16% demonstrated a PAR to GHJ injection. A full thickness tear of supraspinatus on ultrasound was associated with PAR to SAB injection (OR 5.02; <it>p </it>< 0.05). Ultrasound evidence of a biceps tendon sheath effusion (OR 8.0; <it>p </it>< 0.01) and an intact rotator cuff (OR 1.3; <it>p </it>< 0.05) were associated with PAR to GHJ injection. No imaging findings were strongly associated with PAR to ACJ injection (<it>p </it>≤ 0.05).</p> <p>Conclusions</p> <p>Rotator cuff and SAB pathology were the most common findings on ultrasound and MRA. Evidence of a full thickness supraspinatus tear was associated with symptoms arising from the subacromial region, and a biceps tendon sheath effusion and an intact rotator cuff were associated with an intra-articular GHJ pain source. When combined with clinical information, these results may help guide diagnostic decision making in primary care.</p

Predictors of Shoulder Pain and Disability Index (SPADI) and work status after 1 year in patients with subacromial shoulder pain

<p>Abstract</p> <p>Background</p> <p>Shoulder pain is a common complaint in primary health care and has an unfavourable outcome in many patients. The objectives were to identify predictors for pain and disability (SPADI) and work status in patients with subacromial shoulder pain.</p> <p>Methods</p> <p>Secondary analyses of data from a randomized clinical controlled trial were performed. Outcome measures were the absolute values of the combined Shoulder Pain and Disability Index (SPADI) and work status 1 year after treatment with supervised exercises (SE) or radial extracorporeal shockwave therapy (rESWT). Predictors of outcome were investigated using multiple linear regression (SPADI) and logistic regression (work status).</p> <p>Results</p> <p>104 patients were included. Low education (≤ 12 years), previous shoulder pain, and a high baseline SPADI score predicted poor results with these variables explaining 29.9% of the variance in SPADI score at 1 year. Low education and poor self-reported health status predicted a work status of "not working": Odds Ratio, OR = 4.3(95% CI (1.3 to 14.9)), p = 0.02 for education, and OR = 1.06 (95% CI (1.0 to 1.1)), p = 0.001 for self-reported health status, respectively. Adjustments for age, gender, and treatment group were performed, but did not change the results.</p> <p>Conclusion</p> <p>Education was the most consistent predictor of pain and disability, and work status at 1 year follow-up. Also, baseline SPADI score, previous shoulder pain and self-reported health status predicted outcome.</p> <p>Trial registration</p> <p>Clinical trials NCT00653081</p

The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions

Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies

Taping patients with clinical signs of subacromial impingement syndrome: the design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Shoulder problems are a common complaint of the musculoskeletal system. Physical therapists treat these patients with different modalities such as exercise, massage, and shoulder taping. Although different techniques have been described, the effectiveness of taping has not yet been established. The aim of this study is to assess the effectiveness and cost-effectiveness of usual physical therapy care in combination with a particular tape technique for subacromial impingement syndrome of the shoulder compared to usual physical therapy care without this tape technique in a primary healthcare setting.</p> <p>Methods and design</p> <p>An economic evaluation alongside a randomized controlled trial will be conducted. A sample of 140 patients between 18 and 65 years of age with a diagnosis of subacromial impingement syndrome (SAIS) as assessed by physical therapists will be recruited. Eligible patients will be randomized to either the intervention group (usual care in combination with the particular tape technique) or the control group (usual care without this tape technique). In both groups, usual care will consist of individualized physical therapy care. The primary outcomes will be shoulder-specific function (the Simple Shoulder Test) and pain severity (11-point numerical rating scale). The economic evaluation will be performed using a societal perspective. All relevant costs will be registered using cost diaries. Utilities (Quality Adjusted Life Years) will be measured using the EuroQol. The data will be collected at baseline, and 4, 12, and 26 weeks follow-up.</p> <p>Discussion</p> <p>This pragmatic study will provide information about the effectiveness and cost-effectiveness of taping in patients presenting with clinical signs of SAIS.</p> <p>Trial registration</p> <p>Trial registration number: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2575">NTR2575</a></p

All-arthroscopic versus mini-open repair of small or moderate-sized rotator cuff tears: A protocol for a randomized trial [NCT00128076]

BACKGROUND: Rotator cuff tears are the most common source of shoulder pain and disability. Only poor quality studies have compared mini-open to arthroscopic repair, leaving surgeons with inadequate evidence to support optimal, minimally-invasive repair. METHODS/DESIGN: This randomized, multi-centre, national trial will determine whether an arthroscopic or mini-open repair provides better quality of life for patients with small or moderate-sized rotator cuff tears. A national consensus meeting of investigators in the Joint Orthopaedic Initiative for National Trials of the Shoulder (JOINTS Canada) identified this question as the top priority for shoulder surgeons across Canada. The primary outcome measure is a valid quality-of-life scale (Western Ontario Rotator Cuff (WORC)) that addresses 5 domains of health affected by rotator cuff disease. Secondary outcomes will assess rotator cuff functionality (ROM, strength, Constant score), secondary dimensions of health (general health status (SF-12) and work limitations), and repair integrity (MRI). Outcomes are measured at baseline, at 6 weeks, 3, 6, 12, and 24 months post-operatively by blinded research assistants and musculoskeletal radiologists. Patients (n = 250) with small or medium-sized cuff tears identified by clinical examination and MRI who meet eligibility criteria will be recruited. This sample size will provide 80% power to statistically detect a clinically important difference of 20% in WORC scores between procedures after controlling for baseline WORC score (α = 0.05). A central methods centre will manage randomization, data management, and monitoring under supervision of experienced epidemiologists. Surgeons will participate in either conventional or expertise-based designs according to defined criteria to avoid biases from differential surgeon expertise. Mini-open or all-arthroscopic repair procedures will be performed according to a standardized protocol. Central Adjudication (of cases), Trial Oversight and Safety Committees will monitor trial conduct. We will use an analysis of covariance (ANCOVA), where the baseline WORC score is used as a covariate, to compare the quality of life (WORC score) at 2 years post-operatively. As a secondary analysis, we will conduct the same statistical test but will include age and tear size as covariates with the baseline score. Enrollment will require 2 years and follow-up an additional 2 years. The trial will commence when funding is in place. DISCUSSION: These results will have immediate impact on the practice behaviors of practicing surgeons and surgical trainees at JOINTS centres across Canada. JOINTS Canada is actively engaged in knowledge exchange and will publish and present findings internationally to facilitate wider application. This trial will establish definitive evidence on this question at an international level