Summary Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We ...investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Findings Of 10 056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8–4·7) for patients in the no TDR group, 4·7% (2·9–7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9–19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33–4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19–2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9–4·7, p=0·093). Interpretation These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. Funding European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.
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Background Total pancreatectomy (TP) with intraportal islet autotransplantation (IAT) can relieve pain and preserve β-cell mass in patients with chronic pancreatitis (CP) when other therapies fail. ...We report on a >30-year single-center series. Study Design Four hundred and nine patients (including 53 children, 5 to 18 years) with CP underwent TP-IAT from February 1977 to September 2011 (etiology: idiopathic, 41%; Sphincter of Oddi dysfunction/biliary, 9%; genetic, 14%; divisum, 17%; alcohol, 7%; and other, 12%; mean age was 35.3 years, 74% were female; 21% has earlier operations, including 9% Puestow procedure, 6% Whipple, 7% distal pancreatectomy, and 2% other). Islet function was classified as insulin independent for those on no insulin; partial, if known C-peptide positive or euglycemic on once-daily insulin; and insulin dependent if on standard basal–bolus diabetic regimen. A 36-item Short Form (SF-36) survey for quality of life was completed by patients before and in serial follow-up since 2007, with an integrated survey that was added in 2008. Results Actuarial patient survival post TP-IAT was 96% in adults and 98% in children (1 year) and 89% and 98% (5 years). Complications requiring relaparotomy occurred in 15.9% and bleeding (9.5%) was the most common complication. IAT function was achieved in 90% (C-peptide >0.6 ng/mL). At 3 years, 30% were insulin independent (25% in adults, 55% in children) and 33% had partial function. Mean hemoglobin A1c was <7.0% in 82%. Earlier pancreas surgery lowered islet yield (2,712 vs 4,077/kg; p = 0.003). Islet yield (<2,500/kg 36%; 2,501 to 5,000/kg 39%; >5,000/kg 24%) correlated with degree of function with insulin-independent rates at 3 years of 12%, 22%, and 72%, and rates of partial function 33%, 62%, and 24%. All patients had pain before TP-IAT and nearly all were on daily narcotics. After TP-IAT, 85% had pain improvement. By 2 years, 59% had ceased narcotics. All children were on narcotics before, 39% at follow-up; pain improved in 94%; and 67% became pain-free. In the SF-36 survey, there was significant improvement from baseline in all dimensions, including the Physical and Mental Component Summaries (p < 0.01), whether on narcotics or not. Conclusions TP can ameliorate pain and improve quality of life in otherwise refractory CP patients, even if narcotic withdrawal is delayed or incomplete because of earlier long-term use. IAT preserves meaningful islet function in most patients and substantial islet function in more than two thirds of patients, with insulin independence occurring in one quarter of adults and half the children.
Background Chronic pancreatitis is a debilitating disease resulting from many causes. The subset with hereditary/genetic pancreatitis (HGP) not only has chronic pain, but also an increased risk for ...pancreatic cancer. Long-term outcomes of total pancreatectomy (TP) and islet autogeneic transplantation (IAT) for chronic pancreatitis due to HGP are not clear. Study Design We reviewed a prospectively maintained database of 484 TP-IATs from 1977 to 2012 at a single center. The outcomes (eg, pain relief, narcotic use, β-cell function, health-related quality of life measures) of patients who received TP-IAT for HGP (protease trypsin 1, n = 38; serine protease inhibitor Kazal type 1, n = 9; cystic fibrosis transmembrane conductance regulator, n = 14; and familial, n = 19) were evaluated and compared with those with non−hereditary/nongenetic causes. Results All 80 patients with HGP were narcotic dependent and failed endoscopic management or direct pancreatic surgery. Post TP-IAT, 90% of the patients were pancreatitis pain free with sustained pain relief; >65% had partial or full β-cell function. Compared with nonhereditary causes, HGP patients were younger (22 years old vs 38 years old; p ≤ 0.001), had pancreatitis pain of longer duration (11.6 ± 1.1 years vs 9.0 ± 0.4 years; p = 0.016), had a higher pancreas fibrosis score (7 ± 0.2 vs 4.8 ± 0.1; p ≤ 0.001), and trended toward lower islet yield (3,435 ± 361 islet cell equivalent vs 3,850 ± 128 islet cell equivalent; p = 0.28). Using multivariate logistic regression, patients with non-HGP causes (p = 0.019); lower severity of pancreas fibrosis (p < 0.001); shorter duration of years with pancreatitis (p = 0.008); and higher transplant islet cell equivalent per kilogram body weight (p ≤ 0.001) were more likely to achieve insulin independence (p < 0.001). There was a significant improvement in health-related quality of life from baseline by RAND 36-Item Short Form Health Survey and in physical and mental component health-related quality of life scores (p < 0.001). None of the patients in the entire cohort had cancer of pancreatic origin in the liver or elsewhere develop during 2,936 person-years of follow-up. Conclusions Total pancreatectomy and IAT in patients with chronic pancreatitis due to HGP cause provide long-term pain relief (90%) and preservation of β-cell function. Patients with chronic painful pancreatitis due to HGP with a high lifetime risk of pancreatic cancer should be considered earlier for TP-IAT before pancreatic inflammation results in a higher degree of pancreatic fibrosis and islet cell function loss.
Summary Background Back pain remains a challenge for primary care internationally. One model that has not been tested is stratification of the management according to the patient's prognosis (low, ...medium, or high risk). We compared the clinical effectiveness and cost-effectiveness of stratified primary care (intervention) with non-stratified current best practice (control). Methods 1573 adults (aged ≥18 years) with back pain (with or without radiculopathy) consultations at ten general practices in England responded to invitations to attend an assessment clinic. Eligible participants were randomly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group. Primary outcome was the effect of treatment on the Roland Morris Disability Questionnaire (RMDQ) score at 12 months. In the economic evaluation, we focused on estimating incremental quality-adjusted life years (QALYs) and health-care costs related to back pain. Analysis was by intention to treat. This study is registered, number ISRCTN37113406. Findings 851 patients were assigned to the intervention (n=568) and control groups (n=283). Overall, adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months (4·7 SD 5·9 vs 3·0 5·9, between-group difference 1·81 95% CI 1·06–2·57) and at 12 months (4·3 6·4 vs 3·3 6·2, 1·06 0·25–1·86), equating to effect sizes of 0·32 (0·19–0·45) and 0·19 (0·04–0·33), respectively. At 12 months, stratified care was associated with a mean increase in generic health benefit (0·039 additional QALYs) and cost savings (£240·01 vs £274·40) compared with the control group. Interpretation The results show that a stratified approach, by use of prognostic screening with matched pathways, will have important implications for the future management of back pain in primary care. Funding Arthritis Research UK.
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Abstract Background Screening athletes with ECGs is aimed at identifying "at-risk" individuals who may have a cardiac condition predisposing them to sudden cardiac death. The Seattle criteria ...highlight QRS duration greater than 140 ms and ST segment depression in two or more leads greater than 50 μV as two abnormal ECG patterns associated with sudden cardiac death. Methods High school, college, and professional athletes underwent 12 lead ECGs as part of routine pre-participation physicals. Prevalence of prolonged QRS duration was measured using cut-points of 120, 125, 130, and 140 ms. ST segment depression was measured in all leads except leads III, aVR, and V1 with cut-points of 25 μV and 50 μV. Results Between June 2010 and November 2013, 1595 participants including 297 (167 male, mean age 16.2) high school athletes, 1016 (541 male, mean age 18.8) college athletes, and 282 (mean age 26.6) male professional athletes underwent screening with an ECG. Only 3 athletes (0.2%) had a QRS duration greater than 125 ms. ST segment depression in two or more leads greater than 50 μV was uncommon (0.8%), while the prevalence of ST segment depression in two or more leads increased to 4.5% with a cut-point of 25 μV. Conclusion Changing the QRS duration cut-point to 125 ms would increase the sensitivity of the screening ECG, without a significant increase in false-positives. However, changing the ST segment depression cut-point to 25 μV would lead to a significant increase in false-positives and would therefore not be justified.
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Massage therapy is widely recognized as offering many health benefits, with a growing number of studies finding it has value in stress management, pain reduction, and overcoming physical limitations. ...However, there are few studies of massage therapists practices and perceptions in New Zealand and internationally. This paper reports the findings from the first national survey examining the characteristics, perceptions, and experiences of New Zealand-based massage therapists on a range of aspects related to their role and practices.
This study sought to ascertain the characteristics, experiences, and perceptions of massage therapists in New Zealand, particularly in the aspects of: integration of health care; attitudes and practices related to research; and evidence and attitudes to registration.
Massage practice in New Zealand (nationwide survey).
Members of Massage New Zealand (a massage practitioners association).
Massage practitioners were surveyed online, using a 65-part questionnaire, on a range of characteristics of their practices and their attitudes to research, integration, and registration. Statistical analysis was performed using STATA. Statistical significance was set at 0.05.
Four hundred massage therapists (MTs) were invited to participate and 115 responded, providing a response rate of 29%. MTs valued research (95%) and perceived that it had an impact for their practices (88%). Significant correlations were found for research value and: mean case-load (
= .009) and level of academic qualification (
= .004). The majority of MTs (79%) supported integration with conventional practitioners, and 83% referred clients to general practitioners, with 75% receiving referrals from general practitioners. Ninety-three percent of MTs supported registration, with 67% of those supporting statutory registration.
Massage practitioners perceive that they make a significant contribution to health care, but area of practice, such as research, and referral and integration into mainstream health care require more in-depth investigation.
WITHDRAWN: Low back pain across the lifecourse Dunn, Kate M., PhD; Hestbaek, Lise, PhD; Cassidy, J David, PhD, DrMedSci
Best practice & research. Clinical rheumatology,
10/2013
Journal Article
Peer reviewed
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.berh.2013.10.006 The duplicate article has therefore ...been withdrawn.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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