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The effects of nocturnal hemodialysis compared to conventional hemodialysis on change in left ventricular mass: rationale and study design of a randomized controlled pilot study.

BACKGROUND: Nocturnal hemodialysis (NHD) is an alternative to conventional three times per week hemodialysis (CvHD) and has been reported to improve several health outcomes. To date, no randomized controlled trial (RCT) has compared NHD and CvHD. We have undertaken a multi-center RCT in hemodialysis patients comparing the effect of NHD to CvHD on left ventricular (LV) mass, as measured by cardiac magnetic resonance imaging (cMR). METHODOLOGY/DESIGN: All patients in Alberta, Canada, expressing an interest in performing NHD are eligible for the study. Patients enrolled in the study will be randomized to either NHD or CvHD for a six month period. All patients will have a full clinical assessment, including collection of biochemical and cMR data at baseline and at 6 months. Both groups of patients will be monitored biweekly to optimize blood pressure (BP) to a goal of <130/80 mmHg post-dialysis using a predefined BP management protocol. The primary outcome is change in LV mass, a surrogate marker for cardiac mortality, measured at baseline and 6 months. The high sensitivity and reproducibility of cMR facilitates reduction of the required sample size and the time needed between measures compared with echocardiography. Secondary outcomes include BP control, anemia, mineral metabolism, health-related quality of life, and costs. DISCUSSION: To our knowledge, this study will be the first RCT evaluating health outcomes in NHD. The impact of NHD on LV mass represents a clinically important outcome which will further elucidate the potential benefits of NHD and guide future clinical endpoint studies.

Female↗

Effects of high volume saline enemas vs no enema during labour--The N-Ma Randomised Controlled Trial [ISRCTN43153145].

BACKGROUND: Enemas are used during labour in obstetric settings with the belief that they reduce puerperal and neonatal infections, shorten labour duration, and make delivery cleaner for attending personnel. However, a systematic review of the literature found insufficient evidence to support the use of enemas. The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates. METHODS DESIGN: RCT (randomised controlled trial; randomized clinical trial). OUTCOMES: Clinical diagnosis of maternal or neonatal infections, labour duration, delivery types, episiotomy rates, and prescription of antibiotics. SETTING: Tertiary care referral hospital at the Javeriana University (Bogotá, Colombia) that attended 3170 births during study period with a caesarean section rate of 26%. PARTICIPANTS: 443 women admitted for delivery to the obstetrics service (February 1997 to February 1998) and followed for a month after delivery. Inclusion criteria were women with: low risk pregnancy and expected to remain in Bogotá during follow up; gestational age > or = 36 weeks; no pelvic or systemic bacterial infection; intact membranes; cervix dilatation < or = 7 cm. INTERVENTION: 1 litre saline enema, versus no enema, allocated following a block random allocation sequence and using sealed opaque envelopes. RESULTS: Allocation provided balanced groups and 86% of the participants were followed up for one month. The overall infection rate for newborns was 21%, and 18% for women. We found no significant differences in puerperal or neonatal infection rates (Puerperal infection: 41/190 [22%] with enema v 26/182 [14%] without enema; RR 0.66 CI 95%: 0.43 to 1.03; neonatal infection 38/191 [20%] with enema v 40/179 [22%] without enema; RR 1.12, 95% CI 95% 0.76 to 1.66), and median labour time was similar between groups (515 min. with enema v 585 min. without enema; P = 0.24). Enemas didn't significantly change episiorraphy dehiscence rates (21/182 [12%] with enema v 32/190 [17%] without enema; P = 0.30). CONCLUSION: This RCT found no evidence to support routine use of enemas during labour. Although these results cannot rule out a small clinical effect, it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit.

Journal Article↗

Effectiveness of a Minimal Intervention for Stress-related mental disorders with Sick leave (MISS); study protocol of a cluster randomised controlled trial in general practice [ISRCTN43779641].

BACKGROUND: The main aims of this paper are to describe the setting and design of a Minimal Intervention in general practice for Stress-related mental disorders in patients on Sick leave (MISS), as well as to ascertain the study complies with the requirements for a cluster randomised controlled trial (RCT). The potential adverse consequences of sick leave due to Stress-related Mental Disorders (SMDs) are extensive, but often not recognised. Since most people having SMDs with sick leave consult their general practitioner (GP) at an early stage, a tailored intervention given by GPs is justified. We provide a detailed description of the MISS; that is more accurate assessment, education, advice and monitoring to treat SMDs in patients on sick leave. Our hypothesis is that the MISS will be more effective compared to the usual care, in reducing days of sick leave of these patients. METHODS: The design is a pragmatic RCT. Randomisation is at the level of GPs. They received the MISS-training versus no training, in order to compare the MISS vs. usual care at patient level. Enrollment of patients took place after screening in the source population, that comprised 20-60 year old primary care attendees. Inclusion criteria were: moderately elevated distress levels, having a paid job and sick leave for no longer than three months. There is a one year follow up. The primary outcome measure is lasting full return to work. Reduction of SMD- symptoms is one of the secondary outcome measures. Forty-six GPs and 433 patients agreed to participate. DISCUSSION: In our study design, attention is given to the practical application of the requirements for a pragmatic trial. The results of this cluster RCT will add to the evidence about treatment options in general practice for SMDs in patients on sick leave, and might contribute to a new and appropriate guideline. These results will be available at the end of 2006.

Adult↗

The acceptability and impact of a randomised controlled trial of welfare rights advice accessed via primary health care: qualitative study.

BACKGROUND: Qualitative research is increasingly used alongside randomised controlled trials (RCTs) to study a range of factors including participants' experiences of a trial. The need for a sound evidence base within public health will increase the need for RCTs of non-clinical interventions. Welfare rights advice has been proposed as an intervention with potential to reduce health inequalities. This qualitative study, nested within an RCT of the impact of welfare rights advice, examined the acceptability of the intervention, the acceptability of the research process and the perceived impact of the intervention. METHODS: 25 men and women aged 60 years or over were recruited from four general practices in Newcastle upon Tyne (UK), a sub-sample of those who consented to be contacted (n = 96) during the RCT baseline interview. Semi-structured interviews were undertaken and analysed using the Framework Method. RESULTS: Participants viewed the trial positively although, despite agreeing that the information leaflet was clear, some had agreed to participate without being fully aware of what was involved. Some participants were unaware of the implications of randomisation. Most thought it fair, but a few concerns were raised about the control condition. The intervention was acceptable and made participants feel confident about applying for benefit entitlements. 14 out of 25 participants received some financial award; median weekly income gain was pounds 57 (Euro 84, dollar 101). The perceived impact of additional finances was considerable and included: increased affordability of necessities and occasional expenses; increased capacity to deal with emergencies; and a reduction in stress related to financial worries. Overall, perceived independence and ability to participate in society increased. Most participants perceived benefits to their mental well-being, but no-one reported an improvement in physical health. The RCT showed little or no effect on a wide range of outcome measures. CONCLUSION: Participation in the trial and the intervention was acceptable to participants. Welfare rights advice targeted at people aged 60 years or over and accessed via primary care had a positive impact on quality of life and resulted in increased social participation. The divergence of qualitative and quantitative findings suggests that both methods make important contributions to the evaluation of complex social interventions.

Aged↗

Cost effectiveness of a multi-stage return to work program for workers on sick leave due to low back pain, design of a population based controlled trial [ISRCTN60233560].

BACKGROUND: To describe the design of a population based randomized controlled trial (RCT), including a cost-effectiveness analysis, comparing participative ergonomics interventions between 2-8 weeks of sick leave and Graded Activity after 8 weeks of sick leave with usual care, in occupational back pain management. METHODS DESIGN: An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain. Interventions used are 1. Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist. 2. Graded Activity based on cognitive behavioural principles by a physiotherapist. 3. Usual care, provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain. The primary outcome measure is return to work. Secondary outcome measures are pain intensity, functional status and general improvement. Intermediate variables are kinesiophobia and pain coping. The cost-effectiveness analysis includes the direct and indirect costs due to low back pain. The outcome measures are assessed before randomization (after 2-6 weeks on sick leave) and 12 weeks, 26 weeks and 52 weeks after first day of sick leave. DISCUSSION: The combination of these interventions has been subject of earlier research in Canada. The results of the current RCT will: 1. crossvalidate the Canadian findings in an different sociocultural environment; 2. add to the cost-effectiveness on treatment options for workers in the sub acute phase of low back pain. Results might lead to alterations of existing (inter)national guidelines.

Cost-Benefit Analysis↗

Hypertriglyceridemia is associated with prebeta-HDL concentrations in subjects with familial low HDL.

Prebeta-HDL particles act as the primary acceptors of cellular cholesterol in reverse cholesterol transport (RCT). An impairment of RCT may be the reason for the increased risk of coronary heart disease (CHD) in subjects with familial low HDL. We studied the levels of serum prebeta-HDL and the major regulating factors of HDL metabolism in 67 subjects with familial low HDL and in 64 normolipidemic subjects. We report that the subjects with familial low HDL had markedly reduced prebeta-HDL concentrations compared with the normolipidemic subjects (17.4 +/- 7.2 vs. 23.4 +/- 7.8 mg apolipoprotein A-I/dl; P < 0.001). A positive correlation was observed between prebeta-HDL concentration and serum triglyceride (TG) level (r = 0.334, P = 0.006). In addition, serum TG level was found to be the strongest predictor of prebeta-HDL concentration in subjects with familial low HDL. The activities of cholesteryl ester transfer protein and hepatic lipase were markedly increased in subjects with familial low HDL without a significant correlation to prebeta-HDL concentration. Our results support the hypothesis that impaired RCT is one mechanism behind the increased risk for CHD in subjects with familial low HDL.

Adult↗

Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways.

Endocytosis of LDL and modified LDL represents regulated and unregulated cholesterol delivery to macrophages. To elucidate the mechanisms of cellular cholesterol transport and egress under both conditions, various primary macrophages were labeled and loaded with cholesterol or cholesteryl ester from LDL or acetylated low density lipoprotein (AcLDL), and the cellular cholesterol traffic pathways were examined. Confocal microscopy using fluorescently labeled 3,3'-dioctyldecyloxacarbocyanine perchlorate-labeled LDL and 1,1'-dioctyldecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate-labeled AcLDL demonstrated their discrete traffic pathways and accumulation in distinct endosomes. ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I) was much greater for AcLDL-loaded macrophages compared with LDL. Treatment with the liver X receptor ligand 22-OH increased efflux to apoA-I in AcLDL-loaded but not LDL-loaded cells. In contrast, at a level equivalent to AcLDL, LDL-derived cholesterol was preferentially effluxed to HDL, in keeping with increased ABCG1. In vivo studies of reverse cholesterol transport (RCT) from cholesterol-labeled macrophages injected intraperitoneally demonstrated that LDL-derived cholesterol was more efficiently transported to the liver and secreted into bile than AcLDL-derived cholesterol. This indicates a greater efficiency of HDL than lipid-poor apoA-I in interstitial fluid in controlling in vivo RCT. These assays, taken together, emphasize the importance of mediators of diffusional cholesterol efflux in RCT.

ATP Binding Cassette Transporter 1↗

Publication bias of randomized controlled trials in emergency medicine.

OBJECTIVES: To determine the publication status and time to publication of randomized controlled trials (RCTs) that were presented at the Society for Academic Emergency Medicine (SAEM) meetings from 1995 to 2003. The impact of positive-outcome bias, time-lag bias, and gray literature bias also was assessed. METHODS: Retrospective cohort study of RCT abstracts presented at nine SAEM scientific meetings. Electronic searches identified publications from the abstracts. RESULTS: Of 4,399 abstracts, 383 (8.7%; 95% confidence interval [CI] = 7.8% to 9.5%) were identified as RCTs. One hundred ninety-four (50.7%; 95% CI = 45.7% to 55.7%) were subsequently published up to May 2004. The median time to publication was 32 months (95% CI = 23 to 41), with 59% of RCT abstracts published within five years of presentation. No evidence of positive-outcome bias or time-lag bias was identified; however, changes from abstract to manuscript were found. Manuscripts were less likely to endorse the experimental intervention than were abstracts (OR, 0.2; 95% CI = 0.0 to 0.6). CONCLUSIONS: The proportion of emergency medicine RCT abstracts published is slightly lower than that for other biomedical specialties; however, biases reported by investigators in other biomedical areas do not appear to be as problematic in emergency medicine research. Differences between conclusions from abstracts and manuscripts must be considered when employing meeting abstracts as a source of evidence for future research or for systematic reviews in emergency medicine.

Abstracting and Indexing↗

Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results.

PURPOSE: To evaluate our long-term experience with combined modality treatment and selective bladder preservation and to identify factors that may predict treatment response, risk of relapse, and survival. PATIENTS AND METHODS: Between 1982 and 2000, 415 patients with bladder cancer (high-risk T1, n = 89; T2 to T4, n = 326) were treated with radiotherapy (RT; n = 126) or radiochemotherapy (RCT; n = 289) after transurethral resection (TUR) of the tumor. Six weeks after RT/RCT, response was evaluated by restaging-TUR. In case of complete response (CR), patients were observed at regular intervals. In case of persistent or recurrent invasive tumor, salvage-cystectomy was recommended. Median follow-up was 60 months (range, 6 to 199 months). RESULTS: CR was achieved in 72% of patients. Local control after CR without muscle-invasive relapse was maintained in 64% of patients at 10 years. Distant metastases were diagnosed in 98 patients with an actuarial rate of 35% at 10 years. Ten-year disease-specific survival was 42%, and more than 80% of survivors preserved their bladder. Early tumor stage and a complete TUR were the most important factors predicting CR and survival. RCT was more effective than RT alone in terms of CR and survival. Salvage cystectomy for local failure was associated with a 45% disease-specific survival rate at 10 years. Cystectomy because of a contracted bladder was restricted to 2% of patients. CONCLUSION: TUR with RCT is a reasonable option for patients seeking an alternative to radical cystectomy. Ideal candidates are those with early-stage and unifocal tumors, in whom a complete TUR is accomplished.

Adult↗

Stability of parental understanding of random assignment in childhood leukemia trials: an empirical examination of informed consent.

PURPOSE: To examine stability versus change in parental understanding of random assignment in randomized clinical trials (RCTs) for pediatric leukemia and to identify factors associated with changes in understanding. METHODS: Eighty-four parents of children diagnosed with acute lymphoblastic leukemia or acute myeloid leukemia who were enrolled onto a pediatric leukemia RCT at one of six US children's hospitals participated. Parents were interviewed twice, once within 48 hours after the Informed Consent Conference (ICC; time 1 [T1]) and again 6 months later (time 2 [T2]). Interviews focused on parental understanding of key components of the RCT, including random assignment. Interviews were audiotaped, transcribed, and later analyzed. RESULTS: Changes in understanding of random assignment occurred in 19% of parents, with 17% of parents deteriorating in understanding from T1 to T2. Forty-nine percent of parents failed to understand random assignment at both times. Factors associated with understanding at both times included majority ethnicity, high socioeconomic status, parental reading of consent document, and presence of a nurse during the ICC. Physician discussion of specific components of the RCT was also associated with understanding at both times. Female caregivers and parents of low socioeconomic status were overrepresented among those who showed decay in understanding from T1 to T2. CONCLUSION: Parents showed little gain in understanding over time. Factors that predicted understanding at diagnosis as well as sustained understanding over time may be important intervention targets. Attention to both modifiable and nonmodifiable barriers is important for clinical practice.

Adult↗

How do endurance runners actually train? Relationship with competition performance.

PURPOSE: To quantify the relationship between total training load and running performance during the most important competitions of the season (national cross-country championships, 4.175- and 10.130-km races). METHODS: Eight well-trained, subelite endurance runners (age (mean+/-SD): 23+/-2 yr; VO2max: 70.0+/-7.3 mL.kg.min) performed a maximal cardiorespiratory exercise test before the training period to determine ventilatory threshold (VT) and respiratory compensation threshold (RCT). Heart rate was continuously recorded using telemetry during each training session over a 6-month macrocycle, designed to achieve peak performance during the aforementioned cross-country races, lasting from late August to the time that these races were held, that is, mid-February. This allowed us to quantify the total cumulative time spent in three intensity zones calculated as zone 1 (low intensity, lower than the VT); zone 2 (moderate intensity, between VT and RCT); and zone 3 (high intensity, above the RCT). RESULTS: Total training time in zone 1 (4581+/-979 min) was significantly higher (P<0.001) than that accumulated in zones 2 (1354+/-583 min) and 3 (487+/-154 min). Total time in zone 2 was significantly higher than time in zone 3 (P<0.05). A correlation coefficient of r=-0.79 (P=0.06) and r=-0.97 (P=0.008) was found between the total training time spent in zone 1 and performance time during the short and long cross-country races, respectively. CONCLUSIONS: Our findings suggest that total training time spent at low intensities might be associated with improved performance during highly intense endurance events, especially if the event duration is approximately 35 min. Interventional studies (i.e., improving or reducing training time in zone 1) are needed to corroborate our findings and to elucidate the physiological mechanisms behind them.

Adaptation, Physiological↗

Re-infection of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men who have sex with men.

Our aim was to determine the incidence of re-infection of men who have sex with men (MSM) for rectal Neisseria gonorrhoeae (RNg) and rectal Chlamydia trachomatis (RCt) infection. The medical records of 126 MSM diagnosed with RNg or RCt infections at Melbourne Sexual Health Centre were reviewed. A total of 68 of the 126 (54%) MSM were re-tested. Among the HIV-positive MSM, 17 (81%) of 21 were re-tested and eight were positive (47%, 95% confidence interval [CI] 23-72%). Among the 51 (49%) of 105 of the HIV-negative or unknown MSM re-tested, 13 (25%, 14-40) were positive. Of the 21 infections identified, five cases were symptomatic. The incidence of rectal infections among MSM is high and prior RNg or RCt should be included as a risk factor for frequent screening.

Adult↗

Randomized controlled trials: do they have external validity for patients with multiple comorbidities?

PURPOSE: Many randomized controlled trials (RCTs) exclude patients who have multiple comorbidities. The aim of this study was to illustrate the prevalence of comorbidities among patients followed up in primary care who would have met the inclusion criteria of selected RCTs focusing on treatment of a particular condition. We used hypertension as an example of a particular chronic condition. METHODS: We used an existing database of 980 patients (660 women) that was representative of a population consulting primary care family doctors and that contained information about all chronic conditions. We randomly selected 5 RCTs that focused on patients with hypertension. The inclusion and exclusion criteria used in each of the 5 RCTs were applied (1 study at a time) to the patients in our database. The patients from our data set who met the inclusion criteria of a given RCT were considered eligible for that RCT. RESULTS: Of the patients from our data set who were eligible for each of the RCTs, 89% to 100% had multiple chronic conditions. The mean number of chronic conditions of patients eligible for each RCT ranged from 5.5 +/- 3.3 to 11.7 +/- 5.3. CONCLUSIONS: Results from this study suggest that RCTs targeting a chronic medical condition such as hypertension could find that, in a sample taken from family practice, most eligible patients have comorbid conditions. Whether these patients are sampled or excluded should be reported. Research results intended to be applied in medical practice should take the complex reality of effective treatment of these patients into consideration.

Adult↗

Does random treatment assignment cause harm to research participants?

BACKGROUND: Some argue that by precluding individualized treatment, randomized clinical trials (RCTs) provide substandard medical care, while others claim that participation in clinical research is associated with improved patient outcomes. However, there are few data to assess the impact of random treatment assignment on RCT participants. We therefore performed a systematic review to quantify the differences in health outcomes between randomized trial participants and eligible non-participants. METHODS AND FINDINGS: Studies were identified by searching Medline, the Web of Science citation database, and manuscript references. Studies were eligible if they documented baseline characteristics and clinical outcomes of RCT participants and eligible non-participants, and allowed non-participants access to the same interventions available to trial participants. Primary study outcomes according to patient group (randomized trial participants versus eligible non-participants) were extracted from all eligible manuscripts. For 22 of the 25 studies (88%) meeting eligibility criteria, there were no significant differences in clinical outcomes between patients who received random assignment of treatment (RCT participants) and those who received individualized treatment assignment (eligible non-participants). In addition, there was no relation between random treatment assignment and clinical outcome in 15 of the 17 studies (88%) in which randomized and nonrandomized patients had similar health status at baseline. CONCLUSIONS: These findings suggest that randomized treatment assignment as part of a clinical trial does not harm research participants.

Cardiology↗

The potential impact of male circumcision on HIV in Sub-Saharan Africa.

BACKGROUND: A randomized controlled trial (RCT) has shown that male circumcision (MC) reduces sexual transmission of HIV from women to men by 60% (32%-76%; 95% CI) offering an intervention of proven efficacy for reducing the sexual spread of HIV. We explore the implications of this finding for the promotion of MC as a public health intervention to control HIV in sub-Saharan Africa. METHODS AND FINDINGS: Using dynamical simulation models we consider the impact of MC on the relative prevalence of HIV in men and women and in circumcised and uncircumcised men. Using country level data on HIV prevalence and MC, we estimate the impact of increasing MC coverage on HIV incidence, HIV prevalence, and HIV-related deaths over the next ten, twenty, and thirty years in sub-Saharan Africa. Assuming that full coverage of MC is achieved over the next ten years, we consider three scenarios in which the reduction in transmission is given by the best estimate and the upper and lower 95% confidence limits of the reduction in transmission observed in the RCT. MC could avert 2.0 (1.1-3.8) million new HIV infections and 0.3 (0.1-0.5) million deaths over the next ten years in sub-Saharan Africa. In the ten years after that, it could avert a further 3.7 (1.9-7.5) million new HIV infections and 2.7 (1.5-5.3) million deaths, with about one quarter of all the incident cases prevented and the deaths averted occurring in South Africa. We show that a) MC will increase the proportion of infected people who are women from about 52% to 58%; b) where there is homogenous mixing but not all men are circumcised, the prevalence of infection in circumcised men is likely to be about 80% of that in uncircumcised men; c) MC is equivalent to an intervention, such as a vaccine or increased condom use, that reduces transmission in both directions by 37%. CONCLUSIONS: This analysis is based on the result of just one RCT, but if the results of that trial are confirmed we suggest that MC could substantially reduce the burden of HIV in Africa, especially in southern Africa where the prevalence of MC is low and the prevalence of HIV is high. While the protective benefit to HIV-negative men will be immediate, the full impact of MC on HIV-related illness and death will only be apparent in ten to twenty years.

Africa South of the Sahara↗

Association of coronary heart disease with pre-beta-HDL concentrations in Japanese men.

BACKGROUND: In individuals heterozygous for ABCA1 transporter mutations, defective reverse cholesterol transport (RCT) causes low HDL-cholesterol and premature coronary heart disease (CHD). However, the extent to which impaired RCT underlies premature CHD in others with low HDL-cholesterol is not known. The primary acceptors of cell cholesterol are a minor subclass of lipid-poor pre-beta-HDLs. These are generated during remodeling of alpha-HDLs, which account for almost all HDL-cholesterol. We studied the strength of the association of CHD with pre-beta-HDL concentrations in Japanese men. METHODS: Blood was collected from 42 men with clinical CHD and 44 healthy controls 40-70 years of age. Pre-beta-HDL was assayed by crossed immunoelectrophoresis. RESULTS: Cases had lower HDL-cholesterol (-23%), total apolipoprotein A-I (-26%), and pre-beta-HDL (-55%; all P <0.001) concentrations; lower pre-beta-HDL:alpha-HDL ratios (-45%; P <0.001); and higher plasma triglycerides (20%; P <0.03) than the controls. On stepwise logistic regression, CHD was associated most strongly with pre-beta-HDL concentrations. On ROC analysis, pre-beta-HDL concentration discriminated between cases and controls better than any other lipoprotein measurement. When plasma was incubated for 16 h at 37 degrees C, mean (SD) pre-beta-HDL increased by 47 (36)% in controls, but was unchanged in cases (group difference, P <0.001). CONCLUSIONS: Our results suggest that inefficient RCT, secondary to a low pre-beta-HDL concentration and production rate in plasma, contributes to premature CHD in Japanese men with low HDL-cholesterol.

Adult↗

Heliox vs air-oxygen mixtures for the treatment of patients with acute asthma: a systematic overview.

OBJECTIVE: To evaluate, by systematic review, the efficacy of heliox on respiratory mechanics and outcomes in patients with acute asthma. METHODS: The search strategy included searching electronic databases (MEDLINE, EMBASE, and The Cochrane Library) and the references of relevant articles. Study quality was assessed based on allocation concealment. Randomized controlled trials (RCTs) comparing heliox to an air-oxygen mixture (airO(2)) as an adjunct treatment in patients with acute asthmatic attacks were analyzed. For the qualitative portion of the analysis, all reports of the use of heliox in patients with acute asthma were included. RESULTS: Four RCTs (n = 278) were found to have a common respiratory parameter (peak expiratory flow rate as a percentage of predicted) suitable for meta-analysis. Within the 92% confidence interval (CI), there was a small benefit with the use of heliox compared to airO(2) (weighted mean difference, + 3%; 95% CI, - 2 to + 8%). There was also a slight improvement in the dyspnea index (weighted mean difference, 0.60; 95% CI, 0.04 to 1.16) with the use of heliox over airO(2). Overall, five RCTs, one nonrandomized unblinded parallel trial, one retrospective case-matched control trial, three case series, and one case report had results in favor of heliox; one RCT and one case series showed no improvement with heliox; one RCT showed a possible detrimental effect with heliox; and 1 small RCT was inconclusive. Most investigators did not prevent entrainment of room air during heliox use or compensate for the lower nebulizing efficiency of heliox. CONCLUSION: Based on surrogate markers, heliox may offer mild-to-moderate benefits in patients with acute asthma within the first hour of use, but its advantages become less apparent beyond 1 h, as most conventionally treated patients improve to similar levels, with or without it. The effect of heliox may be more pronounced in more severe cases. There are insufficient data on whether heliox can avert tracheal intubation, or change intensive care and hospital admission rates and duration, or mortality.

Acute Disease↗

Effects of hard tissue-related hormones on the intracellular calcium ion of the rat odontoblasts.

We examined the effects of PTH, calcitonin (CT) and parotin subunit on the intracellular Ca2+ of odontoblasts using a chelate reagent, FURA2-AM. Rat CT (rCT), at a final concentration of 0.01 microM, induced a gradual lowering of Ca2+, and addition of ATP, in the presence of CT, resulted in a partial and short-lasting recovery of Ca2+. At higher concentrations, it caused a rapid decrease of Ca2+. CTs of other animal species showed similar effects. Human PTH (hPTH) added at concentrations of 0.01, 0.1 and 1 microM, caused no significant changes in intracellular Ca2+. Parotin subunit caused a rapid lowering of Ca2+ which was seen already at 0.01 microM. rCT added after treatment with hPTH caused an immediate decrease of Ca2+ to zero level, showing that CT action was enhanced by pretreatment with hPTH. This enhancement was also confirmed by addition of hPTH after rCT, where at 1 microM, it caused further acute decrease in Ca2+. After intracellular Ca2+ was lowered by CT pretreatment, parotin, at 0.1 microM, induced a further but gradual decrease of Ca2+. The present results, together with our previous study indicating that hPTH increased cAMP production and that CT inhibited the PTH action, made it clear that all the hormones affect odontoblasts, and that CT and parotin act via Ca-related signal transduction system, while PTH acts via cAMP-PKA-related cascade. Possible crosstalk of both systems was also suggested.

Adenosine Triphosphate↗