Long- or short-acting opioids for chronic non-malignant pain? A qualitative systematic review.

In selected patients with chronic non-malignant pain, chronic opioid therapy is indicated. Published guidelines recommend long-acting over short-acting opioids in these patients. The aim of this systematic review was to investigate whether long-acting opioids in chronic non-malignant pain are superior to short-acting opioids in pain relief, physical function, sleep quality, quality of life or adverse events. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for relevant trials up to July 2012. Reference lists of included trials and relevant reviews were in addition searched by hand. Of the 1168 identified publications, 6 randomised trials evaluating efficacy and safety filled the criteria for inclusion. None of them found a significantly better pain relief, significantly less consumption of rescue analgesia, improved quality of sleep or improved physical function from long-acting opioids. None of the trials investigated quality of life. None of the trials investigated adverse events properly nor addiction, tolerance or hyperalgesia. Three trials in healthy volunteers with a recreational drug use, found no difference in abuse potential between long- and short-acting opioids. While long term, comparative data are lacking, there is fair evidence from short-term trials that long-acting opioids provide equal pain relief compared with short-acting opioids. Contrary to several guidelines, there is no evidence supporting long-acting opioids superiority to short-acting ones in improving functional outcomes, reducing side effects or addiction.

Effect of physical exercise on muscle mass and strength in cancer patients during treatment--a systematic review.

Cancer treatment and its side effects may cause muscle wasting. Physical exercise has the potential to increase muscle mass and strength and to improve physical function in cancer patients undergoing treatment. A systematic review was conducted to study the effect of physical exercise (aerobic, resistance or a combination of both) on muscle mass and strength in cancer patients with different type and stage of cancer disease. Electronic searches were performed up to January 11th 2012, identifying 16 randomised controlled trials for final data synthesis. The studies demonstrated that aerobic and resistance exercise improves upper and lower body muscle strength more than usual care. Few studies have assessed the effect of exercise on muscle mass. Most studies were performed in patients with early stage breast or prostate cancer. Evidence on the effect of physical exercise on muscle strength and mass in cancer patients with advanced disease is lacking. More exercise studies in patients with advanced cancer and at risk of cancer cachexia are warranted.

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33).

AIM/HYPOTHESIS: Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. METHODS: Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. RESULTS: Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 ± 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] ß 0.13, p < 0.001, std ß -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std ß 0.09, p = 0.02), but lost significance after adjustment (std ß 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std ß -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. CONCLUSIONS/INTERPRETATION: In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.

Perceived barriers and facilitators for general practitioner-patient communication in palliative care: a systematic review.

While effective general practitioner (GP)-patient communication is required for the provision of good palliative care, barriers and facilitators for this communication are largely unknown. We aimed to identify barriers and facilitators for GP-patient communication in palliative care. In a systematic review seven computerized databases were searched to find empirical studies on GP-patient communication in palliative care. Fifteen qualitative studies and seven quantitative questionnaire studies were included. The main perceived barriers were GPs' lack of availability, and patients' and GPs' ambivalence to discuss 'bad prognosis'. Main perceived facilitators were GPs being available, initiating discussion about several end-of-life issues and anticipating various scenarios. Lack of availability and failure to discuss former mistakes appear to be blind spots of GPs. GPs should be more forthcoming to initiate discussions with palliative care patients about prognosis and end-of-life issues. Empirical studies are needed to investigate the effectiveness of the perceived barriers and facilitators.

Definitions and incidence of cardiac syndrome X: review and analysis of clinical data.

There is no consensus regarding the definition of cardiac syndrome X (CSX). We systematically reviewed recent literature using a standardized search strategy. We included 57 articles. A total of 47 studies mentioned a male/female distribution. A meta-analysis yielded a pooled proportion of females of 0.56 (n = 1,934 patients, with 95% confidence interval: 0.54-0.59). As much as 9 inclusion criteria and 43 exclusion criteria were found in the 57 articles. Applying these criteria to a population with normal coronary angiograms and treated in 1 year at a general hospital, the attributable CSX incidence varied between 3 and 11%. The many inclusion and exclusion criteria result in a wide range of definitions of CSX and these have large effects on the incidence. This shows the need for a generally accepted definition of CSX.

Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy.

INTRODUCTION: Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors. AIM: The primary aim of the study was to investigate the differential influences of AVF, full and partial bacterial vaginosis, and aerobic vaginitis in the first trimester on PTB rate. The secondary aim was to elucidate why treatment with metronidazole has not been found to be beneficial in previous studies. SETTING: Unselected women with low-risk pregnancies attending the prenatal unit of the Heilig Hart General Hospital in Tienen, Belgium, were included in the study. MATERIALS AND METHODS: At the first prenatal visit, 1026 women were invited to undergo sampling of the vaginal fluid for wet mount microscopy and culture, of whom 759 were fully evaluable. Abnormal vaginal flora (AVF; disappearance of lactobacilli), bacterial vaginosis (BV), aerobic vaginitis (AV), increased inflammation (more than ten leucocytes per epithelial cell) and vaginal colonisation with Candida (CV) were scored according to standardised definitions. Partial BV was defined as patchy streaks of BV flora or sporadic clue cells mixed with other flora, and full BV as a granular anaerobic-type flora or more than 20% clue cells. Vaginal fluid was cultured for aerobic bacteria, Mycoplasma hominis and Ureaplasma urealyticum. Outcome was recorded as miscarriage

Strength training and aerobic exercise training for muscle disease.

BACKGROUND: Strength training or aerobic exercise programmes might maximise muscle and cardiorespiratory function and prevent additional disuse atrophy in patients with muscle disease. However, over-exerting might cause more rapid disease progression. OBJECTIVES: To examine the efficacy and safety of strength training and aerobic exercise training in patients with muscle diseases. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (October 2002 and May 2004), the Cochrane Collaboration Rehabilitation and Related Therapies Field register (October 2002), MEDLINE (January 1966 to December 2002), EMBASE (January 1973 to October 2002), and CINAHL (January 1982 to August 2002) for randomised trials. We reviewed the bibliographies of trials identified and reviews covering the subject. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing strength training and/or aerobic exercise programmes lasting at least 10 weeks. Types of outcome measures: FOR STRENGTH TRAINING. Primary: static or dynamic muscle strength. Secondary: muscle strength (endurance or fatigue), functional assessments, quality of life, muscle membrane permeability, pain, and fatigue. FOR AEROBIC EXERCISE TRAINING. Primary: aerobic capacity expressed as work capacity. Secondary: aerobic capacity (oxygen consumption, parameters of cardiac or respiratory function), functional assessments, quality of life, muscle membrane permeability, pain, and fatigue. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted the data. MAIN RESULTS: We identified two randomised trials fulfilling all inclusion criteria. The first trial compared the effect of strength training versus no training in 36 patients with myotonic dystrophy. The other trial compared strength training versus no training combined with albuterol or placebo in 65 patients with facioscapulohumeral muscular dystrophy. Methodological quality and training programmes were graded adequate. In the myotonic dystrophy trial there were no significant differences between training and non-training groups for the primary outcome measure. In the facioscapulohumeral muscular dystrophy trial static muscle strength did not show significant differences between training and non-training groups. Only a +1.2 kg difference (95% confidence interval 0.2 to 2.1) in dynamic strength of elbow flexors in favour of the training group, reached statistical significance. For both trials there were no significant differences between groups for most of the secondary outcome measures, including those covering adverse effects. AUTHORS' CONCLUSIONS: In myotonic dystrophy and facioscapulohumeral muscular dystrophy moderate-intensity strength training appears not to do harm but there is insufficient evidence to establish that it offers benefit. Limitations in the design of studies in other muscle diseases prevent general conclusions in these disorders.

Ultrasonographic features of the endometrium and the ovaries in women on etonogestrel implant.

OBJECTIVE: To evaluate the ultrasound features of the endometrium and ovaries in women on etonogestrel implant, and to correlate these features with the bleeding pattern. METHODS: Observational study including 188 consecutive women presenting for follow-up transvaginal ultrasound examination after insertion of an etonogestrel implant contraceptive device. Thirty women had more than one follow-up examination. The bleeding pattern was considered abnormal if, in the last 3 months, there were more than five episodes of vaginal bleeding, or there was prolonged bleeding exceeding 14 consecutive days. RESULTS: At first follow-up examination, the mean age was 29.7 years and 47% of women had an abnormal bleeding pattern. Most bleeding episodes were of less intensity than menses. The mean endometrial thickness (ET) on ultrasound was 2.9 mm (standard deviation, 2.0). Ovarian follicle growth exceeding 5 mm was observed in 60% of the cases. Ovulation was demonstrated in one woman. Univariate analysis showed a positive association (P < 0.01) between ET, bleeding pattern, and bleeding intensity. Follicle growth was positively associated (P < 0.01) with ET, bleeding pattern, and interval between insertion and examination. Multivariate analysis showed that the ET was on average 1.25 mm greater in women with abnormal bleeding (P = 0.0001). The odds of finding follicle growth were 2.8 times higher (95% confidence interval, 1.2-6.2) in women presenting with a three-layer type of endometrial morphology. There was no association between the other patients' characteristics and the bleeding pattern. CONCLUSIONS: Abnormal uterine bleeding in women on etonogestrel implant was associated with follicle growth and a thicker, three-layer type of endometrium, suggesting incomplete ovarian inhibition and estrogen stimulation of the endometrium.

Histologic and ultrastructural changes in human endometriotic implants treated with the antiprogesterone steroid ethylnorgestrienone (gestrinone) during 2 months.

In 20 infertile patients, the laparoscopic, histologic, and ultrastructural characteristics of endometriotic implants were studied before and after a 2-month course of therapy using 1.25 mg of the antiprogesterone steroid ethylnorgestrienone daily. Before treatment, well-differentiated endometriotic foci were seen only in implants with a rich microvascular supply. It is postulated that the degree of microvascular development may determine the differentiation of ectopic endometrium. After therapy, well-differentiated endometriotic tissues were recovered in only one patient. In all other patients, the foci remained undifferentiated, while in 11 patients striking epithelial involutionary changes were seen, such as nuclear pyknosis, extrusion of nuclear remnants, enhanced lysosomal autophagy, abortive secretion, and focal epithelial erosion. These histologic and ultrastructural changes reflect a progesterone withdrawal effect in endometriotic implants. It is thus concluded that ethylnorgestrienone induces inactivity in most endometriotic implants, while marked involution is observed in many foci. However, this subcellular involution does not result in a change of the extent of the disease according to the American Fertility Society classification system. Preliminary data concerning the pregnancy rate reveal that five patients conceived during a mean follow-up period of 6 months.