551 research outputs found
Does current reporting of lung function by the UK Cystic Fibrosis Registry allow a fair comparison of adult centres?
Background:Outcome data for UK cystic fibrosis centres are publicly available in an annual report, which ranks centres by median FEV1% predicted. We wished to assess whether there are differences in lung function outcomes between adult centres that might imply differing standards of care.Methods:UK Registry data from 4761 subjects at 34 anonymised adult centres were used to calculate mean FEV1% and rate of change of lung function for 2007–13. These measures were used to rank centres and compare outcomes.Results:There are minor differences between centres for mean FEV1% for some years of the study and for rate of change of lung function over the study period. However, rankings are critically dependent on the outcome measure chosen and centre variation becomes negligible once patient population characteristics are taken into account.Conclusions:We have demonstrated that the ranking of centres is biased and any apparent difference in respiratory outcomes is unlikely to be related to differing standards of care between centres
A case-control study of the locus coeruleus degeneration in Alzheimer’s disease
The locus coeruleus (LC) is the major source of noradrenaline, which plays a key role in cognition. We aimed to detect the extent of the LC signal attenuation in Alzheimer's disease (AD) patients using a neuromelanin (NM)-sensitive MRI and how it may correlate with inflammatory and autonomic measures. An individually matched case-control study design was employed. 24 patients with AD and 24 age and gender matched controls with no cognitive impairment were recruited. The primary outcome measure was the LC signal intensity indicated by the LC contrast ratio (CR) and measured by the NM-sensitive MRI. Secondary outcome measures included neuropsychometric tests of cognitive state, peripheral inflammatory and autonomic measures. Conditional logistic regression analysis revealed a significant 22% LC-CR reduction in the AD group compared with the control group. However, there was no statistical significance from inflammatory or autonomic measures. This is the largest individually-matched case-control study to visualise the LC degeneration in AD patients. The study revealed significant LC degeneration which holds promise to stratify patients who may benefit from treatment targeting noradrenergic dysfunction.</p
Consequences of ignoring clustering in linear regression
Background: clustering of observations is a common phenomenon in epidemiological and clinical research. Previous studies have highlighted the importance of using multilevel analysis to account for such clustering, but in practice, methods ignoring clustering are often employed. We used simulated data to explore the circumstances in which failure to account for clustering in linear regression could lead to importantly erroneous conclusions. Methods: we simulated data following the random-intercept model specification under different scenarios of clustering of a continuous outcome and a single continuous or binary explanatory variable. We fitted random-intercept (RI) and ordinary least squares (OLS) models and compared effect estimates with the “true” value that had been used in simulation. We also assessed the relative precision of effect estimates, and explored the extent to which coverage by 95% confidence intervals and Type I error rates were appropriate. Results: we found that effect estimates from both types of regression model were on average unbiased. However, deviations from the “true” value were greater when the outcome variable was more clustered. For a continuous explanatory variable, they tended also to be greater for the OLS than the RI model, and when the explanatory variable was less clustered. The precision of effect estimates from the OLS model was overestimated when the explanatory variable varied more between than within clusters, and was somewhat underestimated when the explanatory variable was less clustered. The cluster-unadjusted model gave poor coverage rates by 95% confidence intervals and high Type I error rates when the explanatory variable was continuous. With a binary explanatory variable, coverage rates by 95% confidence intervals and Type I error rates deviated from nominal values when the outcome variable was more clustered, but the direction of the deviation varied according to the overall prevalence of the explanatory variable, and the extent to which it was clustered. Conclusions: in this study we identified circumstances in which application of an OLS regression model to clustered data is more likely to mislead statistical inference. The potential for error is greatest when the explanatory variable is continuous, and the outcome variable more clustered (intraclass correlation coefficient is ≥0.01). <br/
Letter from Osmond K. Fraenkel, Esq. to Ernest Besig, Director, American Civil Liberties Union of Northern California, December 17, 1943
Letter from Osmond K. Fraenkel to Ernest Besig enclosing a rough draft of the brief amicus in the Korematsu case.The ACLU-Northern California case file records contain legal documents and correspondence pertaining to the case argued before the Supreme Court in Korematsu v. United States (1944), challenging the constitutionality of Executive Order 9066
Letter from Osmond K. Fraenkel to Ernest Besig, Director, American Civil Liberties Union of Northern California, December 20, 1943
Letter from Osmond K. Fraenkel to Ernest Besig regarding the brief amicus in the Korematsu case, and policy differences between the national ACLU office and the local northern California chapter.The ACLU-Northern California case file records contain legal documents and correspondence pertaining to the case argued before the Supreme Court in Korematsu v. United States (1944), challenging the constitutionality of Executive Order 9066
Effect of administration of intestinal anthelmintic drugs on haemoglobin: systematic review of randomised controlled trials
Objective: To evaluate the effect of routine administration of intestinal anthelmintic drugs on haemoglobin.Design: Systematic review of randomised controlled trials.Data sources: Electronic databases and hand search of reviews, bibliographies of books, and abstracts and proceedings of international conferences.Study selection: Included studies were randomised or quasi-randomised controlled trials using an intestinal anthelmintic agent in the intervention group, in which haemoglobin was evaluated as an outcome measure. Trials in which treatment for schistosoma (praziquantel) was given exclusively to the intervention group were excluded.Results: The search identified 14 eligible randomised controlled trials. Data were available for 7829 subjects, of whom 4107 received an anthelmintic drug and 3722 received placebo. The pooled weighted mean difference (random effect model) of the change in haemoglobin was 1.71 (95% confidence interval 0.70 to 2.73) g/l (P<0.001; test for heterogeneity: Cochran Q=51.17, P<0.001; I2=61% (37% to 76%)). With the World Health Organization's recommended haemoglobin cut-offs of 120 g/l in adults and 110 g/l in children, the average estimated reduction in prevalence of anaemia ranged from 1.1% to 12.4% in adults and from 4.4% to 21.0% in children. The estimated reductions in the prevalence of anaemia increased with lower haemoglobin cut-offs used to define anaemia.Conclusions: Routine administration of intestinal anthelmintic agents results in a marginal increase in haemoglobin (1.71 g/l), which could translate on a public health scale into a small (5% to 10%) reduction in the prevalence of anaemia in populations with a relatively high prevalence of intestinal helminthiasis
Fetal growth in women with homozygous sickle cell disease: an observational study
OBJECTIVES: To assess fetal growth and whether lower birthweight to mothers with homozygous sickle cell (SS) disease is related to maternal body composition or to clinical events in pregnancy.STUDY DESIGN: A prospective study of 41 pregnant women with SS disease and 41 women with a normal (AA) phenotype attending the antenatal clinic, University Hospital of the West Indies, Kingston, Jamaica. Maternal anthropometry, body composition and fetal sonographic measurements were assessed at 15, 25, and 35 weeks' gestation from December 2005 to April 2008. Birth measurements were performed within 24h of delivery. Differences between maternal genotypes and between their offspring were assessed using 2-sample t-tests. Multiple linear regression was used to control for baby's gender and gestational age at delivery. Fetal growth was compared in SS mothers with and without admission for sickle-related complications including bone pain crisis, acute chest syndrome, pregnancy-induced hypertension and urinary tract infection.RESULTS: Mothers with SS disease had lower weight, body fat, fat mass and lean body mass throughout pregnancy but correlation with birth size did not reach statistical significance. Sonographically, babies of SS mothers had smaller abdominal circumference, femoral length and a lower estimated fetal weight at 35 weeks. Birth measurements confirm lower birthweight, crown-heel length and head circumference but the differences were no longer significant after adjustment for baby gender and gestational age at delivery. Bone pain crisis in pregnancy was associated with a significantly reduced crown-heel length at birth.CONCLUSION: Lower birthweight in babies of mothers with SS disease is largely the result of the lower gestational age. Fetal sonography showed no growth differences by maternal genotype until 35 weeks' gestation and a reduced crown-heel length in offspring of SS mothers was associated with bone pain crises in pregnancy
Long-term outcomes of Fine Needle Diathermy for established corneal neovascularisation
BACKGROUND/AIMS:Corneal neovascularisation (CoNV) can lead to significant ocular comorbidity with reduction in vision and cosmesis. A number of techniques have been described to reduce CoNV, but these can be expensive. Our study aimed to determine the safety, efficacy and long-term outcomes of fine needle diathermy (FND) for CoNV.METHODS:A 5-year retrospective study identified all cases of FND. Indications, intraoperative complications, and postoperative visual acuity, after treatment and retreatments, were documented, along with the procedure time. Evidence of regression and number of retreatments were identified.RESULTS:56 eyes from 52 patients underwent FND for CoNV. The main indications included herpes simplex keratitis (HSK) (53%, n=25) and microbial keratitis/peripheral ulcerative keratitis (13%, n=6). Pretreatment acuity was significantly correlated with extent of CoNV (p=0.044). One complication was noted during the procedure-an intrastromal and subconjunctival haemorrhage (rate 2%). 68.1% of patients demonstrated regression at first follow-up (mean 6.9 weeks), and 89.3% (n=42) showed regression with two or less treatments. Mean post-FND acuity was 0.72 (range -0.2-3.0) vs 0.82 (-0.2-3.0) preprocedure (p=0.08). VA improved in the HSK subgroup (p=0.012). Mean follow-up was 18.9 months (range 1-56 months).CONCLUSIONS:In the largest case series reported, FND appears to be a safe and effective technique in the long term to induce regression of CoNV, with significant improvement in the VA of patients with HSK
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