Ingeborg van der Tweel

Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis

BACKGROUND Since the early 1980s, imaging techniques have enabled population-based studies of intracerebral haemorrhage. We aimed to assess the incidence, case fatality, and functional outcome of intracerebral haemorrhage in relation to age, sex, ethnic origin, and time period in studies published since 1980. METHODS From PubMed and Embase searches with predefined inclusion criteria, we identified population-based studies published between January, 1980, and November, 2008. We calculated incidence and case fatality. Incidences for multiple studies were pooled in a random-effects binomial meta-analysis. Time trends of case fatality were assessed with weighted linear-regression analysis. FINDINGS 36 eligible studies described 44 time periods (mid-year range 1983-2006). These studies included 8145 patients with intracerebral haemorrhage. Incidence did not decrease between 1980 and 2008. Overall incidence was 24.6 per 100 000 person-years (95% CI 19.7-30.7). Incidence was not significantly lower in women than in men (overall incidence ratio 0.85, 95% CI 0.61-1.18). Using the age group 45-54 years as reference, incidence ratios increased from 0.10 (95% CI 0.06-0.14) for people aged less than 45 years to 9.6 (6.6-13.9) for people older than 85 years. Median case fatality at 1 month was 40.4% (range 13.1-61.0) and did not decrease over time, and was lower in Japan (16.7%, 95% CI 15.0-18.5) than elsewhere (42.3%, 40.9-43.6). Six studies reported functional outcome, with independency rates of between 12% and 39%. Incidence of intracerebral haemorrhage per 100 000 person-years was 24.2 (95% CI 20.9-28.0) in white people, 22.9 (14.8-35.6) in black people, 19.6 (15.7-24.5) in Hispanic people, and 51.8 (38.8-69.3) in Asian people. INTERPRETATION Incidence of intracerebral haemorrhage increases with age and has not decreased between 1980 and 2006. Case fatality is lower in Japan than elsewhere, increases with age, and has not decreased over time. More data on functional outcome are needed. FUNDING Netherlands Heart Foundation.

Physical activity and breast cancer: a systematic review.

Background: Many epidemiologic studies have found an association between physical activity and breast cancer risk, although this has not been a consistent finding. Methods: Studies were identified through a systematic review of literature available on PubMed through February 2006. We included all cohort and case–control studies that assessed total or leisure time activities in relation to occurrence or mortality of breast cancer. The fully adjusted risk estimates and 95% confidence intervals for the highest versus lowest level of activity were documented for each study as well as evidence for a dose–response relationship. Methodologic quality was also assessed. Due to statistical and methodologic heterogeneity among studies, we did not carry out statistical pooling. To draw conclusions, we performed a best-evidence synthesis taking study quality into account. Results: Nineteen cohort studies and 29 case–control studies were evaluated. There was strong evidence for an inverse association between physical activity and postmenopausal breast cancer with risk reductions ranging from 20% to 80%. For premenopausal breast cancer, however, the evidence was much weaker. For pre- and postmenopausal breast cancer combined, physical activity was associated with a modest (15–20%) decreased risk. Evidence for a dose–response relationship was observed in approximately half of the higher-quality studies that reported a decreased risk. A trend analysis indicated a 6% (95% confidence interval = 3% to 8%) decrease in breast cancer risk for each additional hour of physical activity per week assuming that the level of activity would be sustained. Conclusions: There is evidence for an inverse association between physical activity and breast cancer risk. The evidence is stronger for postmenopausal breast cancer than for premenopausal breast cancer.

Feasibility and effects of the semirecumbent position to prevent ventilator-associated pneumonia: a randomized study.

Context:Reducing aspiration of gastric contents by placing mechanically ventilated patients in a semirecumbent position has been associated with lower incidences of ventilator-associated pneumonia (VAP). The feasibility and efficacy of this intervention in a larger patient population, however, are unknown. Objective:Assessment of the feasibility of the semirecumbent position for intensive care unit patients and its influence on development of VAP. Design:In a prospective multicentered trial, critically ill patients undergoing mechanical ventilation were randomly assigned to the semirecumbent position, with a target backrest elevation of 45°, or standard care (i.e., supine position) with a backrest elevation of 10°. Main Outcome Measures:Backrest elevation was measured continuously during the first week of ventilation with a monitor-linked device. A deviation of position was defined as a change of the randomized position >5°. Diagnosis of VAP was made by quantitative cultures of samples obtained by bronchoscopic techniques. Results:One hundred nine patients were assigned to the supine group and 112 to the semirecumbent group. Baseline characteristics were comparable for both groups. Average elevations were 9.8° and 16.1° at day 1 and day 7, respectively, for the supine group and 28.1° and 22.6° at day 1 and day 7, respectively, for the semirecumbent group (p < .001). The target semirecumbent position of 45° was not achieved for 85% of the study time, and these patients more frequently changed position than supine-positioned patients. VAP was diagnosed in eight patients (6.5%) in the supine group and in 13 (10.7%) in the semirecumbent group (NS), after a mean of 6 (range, 3–9) and 7 (range, 3–12) days, respectively. There were no differences in numbers of patients undergoing enteral feeding, receiving stress ulcer prophylaxis, or developing pressure sores or in mortality rates or duration of ventilation and intensive care unit stay between the groups. Conclusions:The targeted backrest elevation of 45° for semirecumbent positioning was not reached in the conditions of the present randomized study. The achieved difference in treatment position (28° vs. 10°) did not prevent the development of VAP.

Effect of Online Hemodiafiltration on All-Cause Mortality and Cardiovascular Outcomes

In patients with ESRD, the effects of online hemodiafiltration on all-cause mortality and cardiovascular events are unclear. In this prospective study, we randomly assigned 714 chronic hemodialysis patients to online postdilution hemodiafiltration (n=358) or to continue low-flux hemodialysis (n=356). The primary outcome measure was all-cause mortality. The main secondary endpoint was a composite of major cardiovascular events, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, therapeutic coronary intervention, therapeutic carotid intervention, vascular intervention, or amputation. After a mean 3.0 years of follow-up (range, 0.4-6.6 years), we did not detect a significant difference between treatment groups with regard to all-cause mortality (121 versus 127 deaths per 1000 person-years in the online hemodiafiltration and low-flux hemodialysis groups, respectively; hazard ratio, 0.95; 95% confidence interval, 0.75-1.20). The incidences of cardiovascular events were 127 and 116 per 1000 person-years, respectively (hazard ratio, 1.07; 95% confidence interval, 0.83-1.39). Receiving high-volume hemodiafiltration during the trial associated with lower all-cause mortality, a finding that persisted after adjusting for potential confounders and dialysis facility. In conclusion, this trial did not detect a beneficial effect of hemodiafiltration on all-cause mortality and cardiovascular events compared with low-flux hemodialysis. On-treatment analysis suggests the possibility of a survival benefit among patients who receive high-volume hemodiafiltration, although this subgroup finding requires confirmation.

A randomized sequential trial of creatine in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double‐blind, placebo‐controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable‐laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo‐controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS. Ann Neurol 2003;53:437–445

Results and Complications after Ileal Pouch Anal Anastomosis: A Meta-Analysis of 43 Observational Studies Comprising 9,317 Patients

Objective: To analyze the literature of ileal pouch anal anastomosis (IPAA) regarding complications and functional outcome, to provide audit data for individual surgeons and units to assess their own performance against and also to serve as reference standard for the assessment of novel alternatives. Background: IPAA is the standard restorative procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). This operation is, however, associated with distinct rates of failure, complications and fecal incontinence. Methods: A meta-analysis on pooled incidences of complications of IPAA was conducted. Medline search and cross-reference search identified studies on IPAA (n ≧ 50). Two authors independently performed the data extraction on study characteristics, diagnosis, type of operation, pouch-related complications, pouch failure and functional results. In case of disagreement consensus was reached by joint review of the study. Estimates of pouch-related complications, pouch failure and functional results are described as pooled percentages with 95% confidence interval. Results: The initial search based on 1,206 abstracts yielded 43 studies eligible for further analysis. Indications for IPAA were UC in 87.5%, FAP in 8.9% and other diagnoses in 3.6%. The median follow-up was 36.7 months. Pouch failure was 6.8%, increasing to 8.5% in case of follow-up of more than 60 months. Pelvic sepsis occurred in 9.5%. Severe, mild and urge fecal incontinence were reported in 3.7, 17, and 7.3%, respectively.No effect of experience, duration of follow-up and type of surgical technique on the incidence of pouch failure and pelvic sepsis was demonstrable. Conclusions: Current techniques for restorative surgery after proctocolectomy are associated with non-negligible complication rates and leave room for improvement and continuation of development of alternative procedures.

Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies

BACKGROUND Accumulating evidence suggests a sex-dependent role of circulating testosterone in the metabolic syndrome (MetS). METHODS We conducted a meta-analysis of observational studies (PubMed and EMBASE-1 May 2010) relating MetS to determinants of testosterone status [total testosterone (TT), free testosterone (FT) and sex hormone-binding globulin (SHBG)]. RESULTS A total of 52 studies were identified, comprising 22 043 men and 7839 women and presenting relative risk (RR) estimates or hormone levels for subjects with and without MetS. Endogenous TT and FT levels were lower in men with MetS [TT mean difference = -2.64 nmol/l, 95% confidence interval (CI) -2.95 to -2.32; FT standardized mean difference = -0.26 pmol/l, 95% CI -0.39 to -0.13] and higher in women with MetS (TT mean difference = 0.14 nmol/l, 95% CI 0.07-0.20; FT standardized mean difference = 0.52 pmol/l, 95% CI 0.33-0.71) compared with those without. Similarly, men with higher TT levels had a lower MetS risk (RR estimate = 0.38, 95% CI 0.28-0.50) whereas higher TT levels increased the risk of MetS in women (RR estimate = 1.68, 95% CI 1.15-2.45). In both sexes, higher SHBG levels were associated with a reduced risk (men: RR estimate = 0.29, 95% CI 0.21-0.41; women: RR estimate = 0.30, 95% CI 0.21-0.42). CONCLUSION This meta-analysis supports the presence of a sex-dependent association between testosterone and MetS: TT and FT levels are lower in men with MetS, whereas they are higher in women with MetS. There are no indications for a sex-specific association between SHBG and MetS. In both men and women, MetS is associated with lower SHBG levels.

The status of the resection margin as a prognostic factor in the treatment of head and neck carcinoma

The value of the status of the resection margin as a prognostic factor after surgical treatment was investigated in 80 patients with squamous cell carcinoma of the oral cavity, oropharynx and laryngohypopharynx. The relation of locoregional recurrence with the presence or absence of tumour at the surgical margin was analysed together with other indications for postoperative radiotherapy. Locoregional recurrence was observed in 20% and was correlated with tumour thickness over 5 mm, spidery growth and tumour-positive margins. Tumour-positive margin as a single indication for postoperative irradiation was not related to an increased recurrence rate. When however occurring together with other indications for postoperative irradiation, the recurrence rate was higher than in the patient group with the same number of indications for postoperative radiotherapy but without tumour at the surgical margins.

Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis

To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design.

Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients - the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial [ISRCTN38365125]

BackgroundThe high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related to the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) removes these molecules more effectively than standard hemodialysis (HD), it has been suggested that online HDF improves survival and cardiovascular outcome. Thus far, no conclusive data of HDF on target organ damage and cardiovascular morbidity and mortality are available. Therefore, the CONvective TRAnsport STudy (CONTRAST) has been initiated.MethodsCONTRAST is a Dutch multi-center randomised controlled trial. In this trial, approximately 800 chronic hemodialysis patients will be randomised between online HDF and low-flux HD, and followed for three years. The primary endpoint is all cause mortality. The main secondary outcome variables are fatal and non-fatal cardiovascular events.ConclusionThe study is designed to provide conclusive evidence whether online HDF leads to a lower mortality and less cardiovascular events as compared to standard HD.