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Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial.

BACKGROUND: It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART). METHODS: A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS cycles and 141 control cycles). RESULTS: Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer embryos were transferred in the PGD-AS group than in the control group (P<0.001). The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group versus 11.5% in the control group (not significant; P=0.09). We observed a normal diploid status in 36.8% of the embryos. CONCLUSIONS: This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.

Adult↗

Single embryo transfer: a mini-review.

This paper provides a concise review of single embryo transfer (SET) in cycles using fresh embryos as well as in cycles using frozen-thawed embryos. Relevant studies were identified by a computerized search in PubMed for the period 1995-2004. The pregnancy rates, delivery rates and multiple pregnancy/birth rates were evaluated after fresh or frozen embryo transfer as well as cumulative delivery rates after fresh and frozen SET. The results of four randomized controlled trials (RCT) and seven observational studies using fresh embryo transfers are analysed. No RCT with SET in freezing-thawing cycles was identified, while one observational study was identified. The effects of a change in the rules from the National Board of Health and Welfare in Sweden in 2003 regarding the implementation of SET in Sweden are summarized.

Cryopreservation↗

Investigation of staff and patients' opinions of a proposed trial of elective single embryo transfer.

BACKGROUND: In the context of mounting concern about the risks of twin pregnancies resulting from IVF, this study aimed to assess staff and patients' attitudes towards a proposed randomized controlled trial (RCT) of elective single embryo transfer (SET) in a Scottish fertility centre. METHODS: The views of 10 members of IVF clinic staff were assessed by means of a focus group and those of 12 couples by semi-structured interviews. RESULTS: Staff were aware of the risks of twin pregnancies to mothers and babies and the need for evidence of success in SET, but had reservations about the proposed RCT. The need to subject patients to unpopular scientific procedures such as randomization and blinding conflicted with their perceived caring role. They felt it would be hard to recruit and onerous to patients but nevertheless discussed how it could be successfully mounted if necessary. They debated how to ensure that consent was fully informed, and when, and how, to randomize. Patients accepted the possibility of twins but were largely unaware of risks inherent in twin pregnancies. They saw no need for a trial and found the idea of randomization unacceptable except in younger women. They would accept SET if it became unit policy and appeared unaffected by financial considerations. CONCLUSIONS: Involving affected staff at the design stage may make it easier to conduct a SET trial in their clinics. IVF patients whose ultimate goal is pregnancy are less likely to support a trial which aims to minimize twin pregnancies.

Adult↗

Soft versus firm embryo transfer catheters for assisted reproduction: a systematic review and meta-analysis.

BACKGROUND: The true impact of the embryo transfer catheter choice on an IVF programme has not been fully examined. We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter. METHODS: An extensive computerized search was conducted for all relevant articles published as full text, or abstracts, and critically appraised. In addition, a hand search was undertaken to locate any further trials. RESULTS: A total of 23 randomized controlled trials (RCT) evaluating the types of embryo transfer catheters were identified. Only ten of these trials, including 4141 embryo transfers, compared soft versus firm embryo catheters. Pooling of the results demonstrated a statistically significantly increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters [P = 0.01; odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.08-1.79]. When only the truly RCT were analysed, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402)], but with a greater significance (P < 0.00001; OR = 1.49, 95% CI = 1.26-1.77). CONCLUSION: Using soft embryo transfer catheters for embryo transfer results in a significantly higher pregnancy rate as compared to firm catheters.

Catheterization↗

Community pharmacy supply of emergency hormonal contraception: a structured literature review of international evidence.

BACKGROUND: We could find no previous published review of the evidence relating to pharmacy supply of emergency hormonal contraception (EHC). Our objectives were to review, summarize and evaluate the peer-reviewed evidence relating to community pharmacy supply of EHC both in the UK and internationally. METHODS: Systematic searches were conducted for peer-reviewed international research from January 1990 to January 2005. The UK Health Development Agency's Evidence Base 2000 standards and the evidence categories used by the UK Department of Health were applied to each paper. RESULTS: We included 24 peer-reviewed papers. There was one randomized controlled trial (RCT); the remainder of the studies were qualitative or observational studies. Pharmacy supply of EHC enables most women to receive it within 24 h of unprotected sexual intercourse. Services were highly rated by women. One RCT showed that improving access to EHC did not reduce the use of other contraceptives, lead to an increase in risky sexual behaviour or increase the incidence of sexually transmitted infections (STIs). Users expressed some concerns about the appropriateness of receiving additional pharmacist advice regarding future contraception use and STIs. One study found pharmacy supply had led to a decrease in attendances at accident and emergency departments. CONCLUSION: There is good evidence that community pharmacy EHC services provide timely access to treatment and are highly rated by women.

Attitude of Health Personnel↗

Continuous versus cyclic use of combined oral contraceptives for contraception: systematic Cochrane review of randomized controlled trials.

BACKGROUND: With the recent US Food and Drug Administration approval of a combination oral contraceptive that causes a withdrawal bleed every 3 months instead of monthly, avoidance of menstruation through extended or continuous administration (>28 days of active pills) of combined oral contraceptives may become more commonplace for reasons of personal preference rather than limited to treatment of menstrual-associated medical disorders. METHODS: The review aimed to compare contraceptive efficacy, compliance, continuation, satisfaction, bleeding profiles, and menstrual symptoms of combined oral contraceptives with continuous dosing (>28 days of active pills) versus traditional cyclic dosing (21 days of active pills and 7 days of placebo). We searched five computerized databases as well as reference lists of relevant articles for randomized controlled trials (RCT) using continuous or extended combined oral contraceptives for contraception. Two reviewers independently extracted data from eligible articles. RESULTS: Six RCT met inclusion criteria and were of good quality. Contraceptive efficacy and compliance were similar between groups. Discontinuation overall, and for bleeding problems, was not uniformly higher in either group. When studied, participants reported high satisfaction with both dosing regimens. Five out of the six studies found that bleeding patterns were either equivalent or improved with continuous-dosing regimens. The continuous-dosing group had greater improvement of menstrual-associated symptoms (headaches, genital irritation, tiredness, bloating, and menstrual pain). CONCLUSIONS: The variations in pill type and time-interval for continuous dosing make direct comparisons between regimens unfeasible. To allow for comparisons, future studies should choose a previously researched pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.

Adult↗

On randomized controlled trials and lifestyle interventions.

Randomized controlled trials (RCT) are viewed as the ultimate method for evaluation. The author claims that RCT do not enable full evaluation of lifestyle interventions in particular. Lifestyle interventions usually affect several diseases not measured by RCTs and the people who have undergone these interventions also have an impact on the lifestyle in their immediate environment. These potential biases indicate that RCTs underestimate the value of lifestyle interventions.

Bias↗

Investigating patient exclusion bias in meta-analysis.

BACKGROUND: Trial investigators frequently exclude patients from trial analyses which may bias estimates of the effect of treatment. Combining these estimates in a meta-analysis could aggregate any such biases. METHODS: To investigate how excluding patients from trials can affect the results of both trials and meta-analyses, we used 14 meta-analyses of individual patient data (IPD) that addressed therapeutic questions in cancer. These included 133 randomized controlled trials (RCT) and 21 905 patients. We explored whether exclusions were related to trial characteristics and categorized the reasons for exclusions. For each RCT and meta-analysis, we compared results of an intention-to-treat analysis of all randomized patients with an analysis based on those patients included in the investigators' analysis. RESULTS: In all, 92 trials (69%) excluded between 0.3 and 38% of patients randomized. Trials excluding patients tended to be older and larger than those that did not. Most patients were excluded because of ineligibility or protocol violations. Exclusions varied substantially by meta-analysis, more patients tending to be excluded from the treatment arm. Comparing trial analyses there was no clear indication that exclusion of patients altered the results more in favour of either treatment or control. However, comparing meta-analysis results, there was a tendency for those based on 'included' patients to favour the research treatment (P = 0.03). Inconsistency of trial results was often increased as a result of the investigators' exclusions. CONCLUSIONS: Trials, systematic reviews, and meta-analyses may be prone to bias associated with post-randomization exclusion of patients. Wherever possible, the level of such exclusions should be taken into account when assessing the potential for bias in trials, systematic reviews, and meta-analyses. Ideally, trials, systematic reviews, and meta-analyses should be based on all randomized patients.

Bias↗

Patterns of care study for postmastectomy radiotherapy in Japan: its role in monitoring the patterns of changes in practice.

BACKGROUND: Three prospective randomized clinical trials (RCT) in the 1990s demonstrated the survival benefit of postmastectomy radiotherapy (PMRT) for patients with locally advanced breast cancer. The present study was performed to evaluate whether the Patterns of Care Study (PCS) fulfills a role in monitoring the patterns of changes in clinical practices in Japan. METHODS: The first survey (JPCS-1) involved 79 Japanese facilities by two-stage cluster sampling of facilities and patients, and was carried out during 1998-2000. JPCS-1 included 1124 patients with breast cancer who were treated between 1995 and 1997. The second survey (JPCS-2) was carried out during 2001-2003, involving 827 patients who were treated between 1999 and 2001 in 76 facilities. RESULTS: Patients with adverse risk factors, including pathologically axillary positive nodes (> or =4) and/or advanced primary disease (pT3-4) accounted for 57% of the patients who received PMRT in JPCS-1 and 72% of those in JPCS-2 (P = 0.039). The multiple radiotherapy target volume including the chest wall and regional lymph nodes was applied in 18% of the patients in JPCS-1 and 44% of those in JPCS-2 (P < 0.001). However, the dose distribution was calculated in only 42% of the patients in both surveys (P = 0.467). CONCLUSIONS: The eligibility and the target volume for PMRT were influenced by the outcome of RCT, but the quality of radiotherapy did not improve sufficiently. The PCS survey is useful to monitor the changes in patterns of clinical practice and can clarify some problems with radiotherapy techniques.

Aged↗

Trans fatty acids affect lipoprotein metabolism in rats.

This study was designed to investigate the effects of oleic (CIS), palmitic (SAT) and trans fatty acids (TRANS) on cholesterol metabolism. Rats fed the TRANS diet had lower plasma total cholesterol (P < 0.005) and non-HDL-cholesterol (non HDL-C) concentrations (P < 0.005) compared with their CIS-fed counterparts. Plasma HDL-C was highest in rats fed the SAT diet (P = 0.01). An in vivo assay of reverse cholesterol transport (RCT) was performed whereby radiolabeled cholesterol was delivered to the liver as acetylated LDL and the reappearance of label into plasma and HDL was determined. Plasma radioactivity in TRANS-fed rats was lower than in their SAT-fed counterparts (P = 0.01), and consistent with the cholesterol distribution in plasma, the difference was due to lower [(3)H]-cholesterol in lower density lipoproteins. Despite diet-induced differences in the cholesterol and phospholipid concentrations and fatty acid composition of HDL, the amount of label in HDL did not differ among groups, suggesting that consumption of these diets resulted in HDL populations with similar capacity to participate in RCT. The present findings suggest that dietary trans fatty acids regulate the metabolism of apolipoprotein B-containing lipoproteins in rats and that the effect may be masked in species possessing high plasma cholesteryl ester transfer protein (CETP) activity. These results reinforce the important role of CETP activity in determining the distribution of plasma cholesterol in response to dietary trans fatty acids.

Animals↗

Dietary fats differentially modulate the expression of lecithin:cholesterol acyltransferase, apoprotein-A1 and scavenger receptor b1 in rats.

In the present study the effects of dietary fat with defined fatty acids on lecithin:cholesterol acyltransferase (LCAT) and apoA-1, the two components of HDL that play a major role in reverse cholesterol transport (RCT), were examined. In addition, the expression of scavenger receptor B1 (SR-B1), the receptor involved in the uptake of HDL core lipids, was also determined under the same conditions in rats fed semisynthetic diets supplemented with triolein (TO), tripalmitin (TP) or menhaden oil (MO). Serum LCAT activity [ micro mol CE/(L.h)] was significantly (P < 0.05) higher in rats fed TO (33 +/- 4) compared with those fed TP (23 +/- 3) or MO (21 +/- 1). The levels of hepatic LCAT mRNA and hepatic SR-B1 receptor protein did not differ between rats fed TP and MO. The triolein diet, on the other hand, increased the induction of hepatic LCAT mRNA and hepatic SR-B1 receptor protein 1.5- to 2-fold. Serum HDL cholesterol concentrations differed among all groups and were 1.30 +/- 0.08, 1.17 +/- 0.10 and 0.91 +/- 0.06 mmol/L for TO-, TP- and MO-fed rats, respectively. Serum apoA-1 levels were significantly higher in TO-fed rats than in the other two groups. The data indicate that TO increases the secretion of HDL and its components (apoA-1 and LCAT), and stimulates the production of hepatic SR-B1 receptor protein. Overall, these results suggest that triolein may promote RCT and thus retard the development of atherosclerosis.

Animals↗

Development of ribozyme synthesis system using a rolling-synchronization: effect of template DNA secondary structure on recognition of RNA polymerase.

Circular DNA behaves as an efficient template for RNA polymerase (RNAP) in rolling circle transcription (RCT). We found that the short hairpin-stem structure in the circular DNA without promoter enhances the DNA recognition of T7 RNAP in RCT. The result indicates that T7 RNAP would distinguish the short DNA hairpin-stem structure.

Base Sequence↗

Cellular cholesterol efflux to plasma from proteinuric patients is elevated and remains unaffected by antiproteinuric treatment.

BACKGROUND: Lipid derangements are assumed to contribute to the elevated cardiovascular risk in proteinuric patients. The impact of proteinuria on reverse cholesterol transport (RCT) is unknown. The first step in RCT, cellular cholesterol efflux to plasma, may be altered in proteinuria, consequent to changes in pre-beta high-density lipoprotein (HDL) formation and plasma phospholipid transfer protein (PLTP) activity. METHODS: In six non-diabetic male patients with nephrotic-range proteinuria and 12 matched healthy men, plasma (apo)lipoproteins, pre-beta HDL formation, PLTP activity as well as the ability of plasma to promote cholesterol efflux out of cultured human skin fibroblasts were determined. These variables were also measured in response to antiproteinuric treatment, consisting of single and dual RAAS blockade by losartan and lisinopril. RESULTS: Plasma total cholesterol (P<0.05), triglycerides (P<0.05), apolipoprotein (apo) A-I (P<0.001), apo B (P<0.001), PLTP activity (P<0.005) and pre-beta HDL formation (P<0.001) were higher in proteinuric patients. Cellular cholesterol efflux to plasma from proteinuric patients was 41% higher than to plasma from healthy subjects (P<0.001). Reduction of proteinuria from 5.0 to 1.4 g/day by dual RAAS blockade was associated with a 23% reduction in plasma apo B levels (P<0.05). Pre-beta HDL formation and plasma PLTP activity did not change significantly. Combined antiproteinuric treatment did not reduce the elevated cellular cholesterol efflux. CONCLUSION: Cellular cholesterol efflux to plasma from patients with nephrotic-range proteinuria is enhanced, in conjunction with elevated pre-beta HDL formation and plasma PLTP activity. These changes may attenuate the cardiovascular risk associated with proteinuria-associated hyperlipidaemia. Antiproteinuric therapy lowers plasma apo B, but does not affect cell-derived cholesterol efflux, suggesting that this therapy beneficially affects cardiovascular risk in proteinuric patients.

Adult↗

Evaluating computerized health information systems: hardware, software and human ware: experiences from the Northern Province, South Africa.

Despite enormous investment world-wide in computerized health information systems their overall benefits and costs have rarely been fully assessed. A major new initiative in South Africa provides the opportunity to evaluate the introduction of information technology from a global perspective and assess its impact on public health. The Northern Province is implementing a comprehensive integrated hospital information system (HIS) in all of its 42 hospitals. These include two mental health institutions, eight regional hospitals (two acting as a tertiary complex with teaching responsibilities) and 32 district hospitals. The overall goal of the HIS is to improve the efficiency and effectiveness of health (and welfare) services through the creation and use of information, for clinical, administrative and monitoring purposes. This multi-site implementation is being undertaken as a single project at a cost of R130 million (which represents 2.5 per cent of the health and welfare budget on an annual basis). The implementation process commenced on 1 September 1998 with the introduction of the system into Mankweng Hospital as the pilot site and is to be completed in the year 2001. An evaluation programme has been designed to maximize the likelihood of success of the implementation phase (formative evaluation) as well as providing an overall assessment of its benefits and costs (summative evaluation). The evaluation was designed as a form of health technology assessment; the system will have to prove its worth (in terms of cost-effectiveness) relative to other interventions. This is more extensive than the traditional form of technical assessment of hardware and software functionality, and moves into assessing the day-to-day utility of the system, the clinical and managerial environment in which it is situated (humanware), and ultimately its effects on the quality of patient care and public health. In keeping with new South African legislation the evaluation process sought to involve as many stakeholders as possible at the same time as creating a methodologically rigorous study that lived within realistic resource limits. The design chosen for the summative assessment was a randomized controlled trial (RCT) in which 24 district hospitals will receive the HIS either early or late. This is the first attempt to carry out an RCT evaluation of a multi-site implementation of an HIS in the world. Within this design the evaluation will utilize a range of qualitative and quantitative techniques over varying time scales, each addressing specific aims of the evaluation programme. In addition, it will attempt to provide an overview of the general impact on people and organizations of introducing high-technology solutions into a relatively unprepared environment. The study should help to stimulate an evaluation culture in the health and welfare services in the Northern Province as well as building the capacity to undertake such evaluations in the future.

Computers↗

Oximes in acute organophosphorus pesticide poisoning: a systematic review of clinical trials.

BACKGROUND: Acute organophosphorus (OP) pesticide poisoning is widespread in the developing world. Standard treatment involves the administration of intravenous atropine and an oxime to counter acetylcholinesterase inhibition at the synapse, but the usefulness of oximes is uncertain. AIM: To assess the evidence on the use of oximes in OP poisoning. DESIGN: Systematic review. METHODS: We searched Medline, Embase, and Cochrane databases (last check 01/02/02) for 'organophosphate' or 'oxime' together with 'poisoning' or 'overdose'. We cross-referenced from other articles, and contacted experts to identify unpublished studies. A Web search engine [www.google.com] was also used, with the keywords 'organophosphate', 'oxime', and 'trial' (last check 01/02/02). RESULTS: We found two randomized controlled trials (RCTs) involving 182 patients treated with pralidoxime. The RCTs found no benefit with pralidoxime, and have been used to argue that pralidoxime should not be used in OP poisoning. DISCUSSION: The RCT authors must be congratulated for attempting important studies in a difficult environment. However, their studies did not take into account recently clarified issues regarding outcome, and their methodology is unclear. A generalized statement that pralidoxime should not be used in OP poisoning is not supported by the published results. Oximes may well be irrelevant in the overwhelming self-poisoning typical of the tropics, but a large RCT comparing the current WHO-recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/h infusion) with placebo is needed for a definitive answer. Such a study should be designed to identify any patient subgroups that might benefit from oximes.

Acute Disease↗

A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal.

INTRODUCTION: Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to treat rheumatoid arthritis (RA). Early trials showed their toxicity while recent trials suggest superior efficacy. Trials of DMARD combinations have enrolled different types of patient (early or established RA), used different designs (step-up, parallel or step-down) and utilized a range of outcome measures. We undertook a systematic review of combination DMARD therapy for RA and carried out a meta-analysis to evaluate the evidence for efficacy and toxicity. METHOD: Medline, PubMed and EmBase were searched using MESH headlines 'arthritis, rheumatoid', 'drug therapy, combination' and 'randomized controlled trial' (RCT) for papers published from 1975 to April 2004. References from published articles were also searched. Three independent assessors evaluated abstracts and selected trials for detailed examination. Trials were excluded if their quality was poor, were not published in English or studied DMARDs not licensed to treat RA. Two independent assessors extracted data. Efficacy was assessed by the numbers of patients withdrawn due to lack of efficacy. Toxicity was assessed by the numbers of patients withdrawn due to adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were calculated and meta-analysis was carried out based on a random effects model. Sensitivity analyses evaluated different treatment combinations, trial designs, study populations and outcome measures. RESULTS: Fifty-three potentially relevant RCTs were identified. Twelve were excluded due to: using unlicensed DMARDs (n = 3); reporting in journal supplements of RCTs already included (n = 2); follow-up of an earlier RCT, report of biological outcomes or pharmacokinetics (n = 5); and non-English language publications (n = 2). Forty-one RCTs were evaluated in detail and another five excluded (three open-labelled studies and two with high patient attrition); 36 studies were included in the meta-analysis. These comprised 13 step-up, 16 parallel and 7 step-down trials. Nine assessed early RA and 27 established RA. Seven added steroids to DMARD monotherapy and one study added steroids to DMARD combinations. Six assessed methotrexate (MTX) plus tumour necrosis factor (TNF) inhibitors. Overall, combination DMARD therapy was more effective than monotherapy (RR 0.35; 95% CI 0.28, 0.45) although the risk of toxicity was also slightly higher (RR 1.37; 95% CI 1.16, 1.62). Combinations of MTX with TNF inhibitors and MTX with sulphasalazine or anti-malarials showed good efficacy/toxicity ratios. CONCLUSIONS: DMARD combinations vary in their efficacy/toxicity ratio. MTX plus sulphasalazine and/or anti-malarials and MTX plus TNF inhibitors have particularly favourable benefit/risk ratios.

Antirheumatic Agents↗

A cost consequences analysis of local corticosteroid injection and physiotherapy for the treatment of new episodes of unilateral shoulder pain in primary care.

OBJECTIVE: Local steroid injections and community-based physiotherapy have been shown to be of similar benefit for treating shoulder pain presenting to primary care. This paper presents a cost consequences analysis of a prospective economic evaluation, conducted alongside a randomized clinical trial (RCT) of corticosteroid injections versus physiotherapy for new episodes of unilateral shoulder pain, to determine the economic implications of injection versus physiotherapy. METHODS: A pragmatic RCT with 207 patients randomized to either physiotherapy (n = 103) or local steroid injection (n = 104) was conducted. The resource inputs required were identified for each treatment arm in terms of capital, staff and consumables. These were measured for the period up to 6 months post-randomization. Outcome measures included shoulder disability, shoulder pain, global assessment of health change and the EQ5D, all at 6 months. A sensitivity analysis was performed around the general practitioner minor surgical fee. RESULTS: Analysis is presented on the 199 patients for which the general practice record review (101 physiotherapy, 98 injection) was available. The total mean costs, per patient, were 71.28 pound sterling for the injection group and 114.60 pound sterling for the physiotherapy group. The difference in average total cost per patient was 43.32 pound sterling (95% bootstrap confidence interval: 16.21 pound sterling, 68.03 pound sterling ). This is a statistically significant difference in cost. Outcome was similar in both groups across all measures following intervention. Smaller mean differences in cost were observed between the treatment groups in the sensitivity analysis, but the difference remained in favour of injection over physiotherapy. CONCLUSIONS: This study has shown, given similar clinical outcomes across the treatment groups, that corticosteroid injections were the cost-effective option for patients presenting with new episodes of unilateral shoulder pain in primary care.

Adult↗

In vitro diagnosis of malignant hyperthermia susceptibility with ryanodine-induced contractures in human skeletal muscles.

The in vitro contracture test with ryanodine is a new method to distinguish malignant hyperthermia (MH) susceptible (MHS) from normal (MHN) patients. The purpose of our investigation was to determine whether smaller concentrations of ryanodine than those used previously may result in a better differentiation. We performed a ryanodine contracture test (RCT) using concentrations of 1 and 2 microM in muscle specimens of 41 MHS, 58 MHN, and 19 MH-equivocal (MHE) patients. Nine patients were excluded from the study due to neuromuscular diseases. All contracture levels (i.e., start of contractures, contractures of 0.2 g and 1.0 g) were attained significantly earlier in MHS than in MHN muscles at both concentrations of ryanodine. Using a ryanodine concentration of 2 microM, all contracture levels were reached significantly faster than with 1 microM. There was no overlap in the range of times between groups at all contracture levels with ryanodine 1 and 2 microM. The median threshold times for all MHE patients were always between those of MHS and MHN. Defining arbitrarily threshold times for MHS and MHN, an assignment of MHE patients to either MHS or MHN using 1 or 2 microM ryanodine was possible in most cases. Ryanodine administration at a concentration of 1 microM led to a better distinction of MHS from MHN patients than 2 microM. The RCT with ryanodine 1 microM should therefore be added to the current diagnostic methods.

Adolescent↗