E. coli bacteraemia and antimicrobial resistance following antimicrobial prescribing for urinary tract infection in the community

Background: Urinary tract infections are one of the most common infections in primary and secondary care, with the majority of antimicrobial therapy initiated empirically before culture results are available. In some cases, however, over 40% of the bacteria that cause UTIs are resistant to some of the antimicrobials used, yet we do not know how the patient outcome is affected in terms of relapse, treatment failure, progression to more serious illness (bacteraemia) requiring hospitalization, and ultimately death. This study analyzed the current patterns of antimicrobial use for UTI in the community in Scotland, and factors for poor outcomes. Objectives: To explore antimicrobial use for UTI in the community in Scotland, and the relationship with patient characteristics and antimicrobial resistance in E. coli bloodstream infections and subsequent mortality. Methods: We included all adult patients in Scotland with a positive blood culture with E. coli growth, receiving at least one UTI-related antimicrobial (amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, trimethoprim, and nitrofurantoin) between 1st January 2009 and 31st December 2012. Univariate and multivariate logistic regression analysis was performed to understand the impact of age, gender, socioeconomic status, previous community antimicrobial exposure (including long-term use), prior treatment failure, and multi-morbidity, on the occurrence of E. coli bacteraemia, trimethoprim and nitrofurantoin resistance, and mortality. Results: There were 1,093,227 patients aged 16 to 100 years old identified as receiving at least one prescription for the 5 UTI-related antimicrobials during the study period. Antimicrobial use was particularly prevalent in the female elderly population, and 10% study population was on long-term antimicrobials. The greatest predictor for trimethoprim resistance in E. coli bacteraemia was increasing age (OR 7.18, 95% CI 5.70 to 9.04 for the 65 years old and over group), followed by multi-morbidity (OR 5.42, 95% CI 4.82 to 6.09 for Charlson Index 3+). Prior antimicrobial use, along with prior treatment failure, male gender, and higher deprivation were also associated with a greater likelihood of a resistant E. coli bacteraemia. Mortality was significantly associated with both having an E. coli bloodstream infection, and those with resistant growth. Conclusion: Increasing age, increasing co-morbidity, lower socioeconomic status, and prior community antibiotic exposure were significantly associated with a resistant E. coli bacteraemia, which leads to increased mortality

Linear mixed models for longitudinal shape data with applications to facial modelling

We present a novel application of methods for analysis of high-dimensional longitudinal data to a comparison of facial shape over time between babies with cleft lip and palate and similarly aged controls. A pairwise methodology is used that was introduced in Fieuws and Verbeke (2006) in order to apply a linear mixed-effects model to data of high dimensions, such as describe facial shape. The approach involves fitting bivariate linear mixed-effects models to all the pairwise combinations of responses, where the latter result from the individual coordinate positions, and aggregating the results across repeated parameter estimates (such as the random-effects variance for a particular coordinate). We describe one example using landmarks and another using facial curves from the cleft lip study, the latter using B-splines to provide an efficient parameterization. The results are presented in 2 dimensions, both in the profile and in the frontal views, with bivariate confidence intervals for the mean position of each landmark or curve, allowing objective assessment of significant differences in particular areas of the face between the 2 groups. Model comparison is performed using Wald and pseudolikelihood ratio tests

Negative symptoms and psychosocial functioning in schizophrenia: neglected but important targets for treatment

<p>Background: Many patients with schizophrenia suffer from poor social functioning, with high levels of unemployment being one particular consequence. Negative symptoms tend to persist during periods of clinical stability and may have a detrimental effect on function. This paper aims to investigate the relationship between negative symptoms and ability to function.</p> <p>Methods: The EGOFORS study measured negative symptoms in 295 schizophrenia patients in 11 European sites using the PANSS Negative Subscale and assessment scales for psychosocial function: Global Assessment of Functioning (GAF), Personal and Social Performance (PSP), Quality of Life Scale (QLS), Functional Remission of General Schizophrenia (FROGS), Psychosocial Remission in Schizophrenia (PSRS) and Subjective Wellbeing under Neuroleptics (SWN). The relationships between the PANSS Negative Subscale and the functional scales were investigated, adjusting for differences between study sites. Being in work, duration of illness, age of onset and number of years of education were also investigated for a relationship with function.</p> <p>Results: There were strong, statistically significant correlations between PANSS Negative Subscale and all of the function scales (95% confidence intervals for the correlation coefficients: PSRS 0.77–0.91; FROGS 0.74–0.89; QLS 0.74–0.92; GAF 0.64–0.78; PSP 0.63–0.80) except the SWN. All of the functional scales except SWN were at least moderately related to one another. All of the items in each of the PANSS Negative Subscale and the function scales contributed to the relationships between them. Better functioning correlated strongly with participants being in work.</p> <p>Conclusion: This study shows a strong and significant relationship between negative symptoms and psychosocial functioning. Given the impact of negative symptoms on psychosocial function, much more emphasis should be placed on developing effective treatments for negative symptoms, given that most patients with schizophrenia now live in community settings and require to function adequately to support their quality of life.</p&gt

Systematic review of schizophrenia

<p>INTRODUCTION: The prevalence of schizophrenia is thought to be about one in 100; about 75% of people have relapses and continued disability, and one third fail to respond to standard treatment. Positive symptoms include auditory hallucinations, delusions, and thought disorder. Negative symptoms (demotivation, self-neglect, and reduced emotion) have not been consistently improved by any treatment.</p> <p>METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for positive, negative, or cognitive symptoms of schizophrenia? What are the effects of interventions in people with schizophrenia who are resistant to standard antipsychotic drugs? What are the effects of interventions to improve adherence to antipsychotic medication in people with schizophrenia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).</p> <p>RESULTS: We found 51 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.</p> <p>CONCLUSIONS: In this systematic review, we present information relating to the effectiveness and safety of the following interventions: behavioural therapy, clozapine, cognitive behavioural therapy (CBT), compliance therapy, first-generation antipsychotic drugs in treatment-resistant people, multiple-session family interventions, psychoeducational interventions, second-generation antipsychotic drugs in treatment-resistant people, and social-skills training.</p&gt

Patterns of treatment response in newly diagnosed epilepsy

<p>Objective: To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy.</p> <p>Methods: Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982 and April 1, 2006, were followed up until March 31, 2008. Outcomes were categorized into four patterns: (A)early and sustained seizure freedom; (B)delayed but sustained seizure freedom; (C)fluctuation between periods of seizure freedom and relapse; (D)seizure freedom never attained. Probability of seizure freedom with successive drug regimens was compared. Seizure freedom was defined as no seizures for ≥1 year.</p> <p>Results: A total of 1,098 patients were included (median age 32 years, range 9 to 93). At the last clinic visit, 749(68%) patients were seizure-free, 678(62%) on monotherapy. Outcome pattern A was observed in 408(37%), pattern B in 246(22%), pattern C in 172(16%) and pattern D in 272(25%) patients. There was a higher probability of seizure freedom in patients receiving one compared to two drug regimens, and two compared to three regimens (p<0.001). The difference was greater among patients with symptomatic or cryptogenic than with idiopathic epilepsy. Less than 2% of patients became seizure-free on subsequent regimens but a few did so on their sixth or seventh regimen.</p> <p>Conclusions: Most patients with newly diagnosed epilepsy had a constant course which could usually be predicted early. The chance of seizure freedom declined with successive drug regimens, most markedly from the first to the third and among patients with localization-related epilepsies.</p&gt

A randomised double-blind placebo-controlled trial to determine the effect of cranberry juice on decreasing the incidence of urinary symptoms and urinary tract infections in patients undergoing radiotherapy for cancer of the bladder or cervix

Aims: Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix. Materials and methods: The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration. Results: The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P = 0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14–1.63). Conclusions: The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study

Is there cognitive decline 1 year after CABG? Comparison with surgical and nonsurgical controls

<p><b>Background:</b> It is widely assumed that decline in cognition after coronary artery bypass grafting (CABG) is related to use of the cardiopulmonary bypass pump. Because most studies have not included comparable control groups, it remains unclear whether postoperative cognitive changes are specific to cardiopulmonary bypass, general aspects of surgery, or vascular pathologies of the aging brain.</p> <p><b>Methods:</b> This nonrandomized study included four groups: CABG patients (n = 140); off-pump coronary surgery (n = 72); nonsurgical cardiac controls (NSCC) with diagnosed coronary artery disease but no surgery (n = 99); and heart healthy controls (HHC) with no cardiac risk factors (n = 69). Subjects were evaluated at baseline (preoperatively), 3 months, and 12 months. Eight cognitive domains and a global cognitive score, as well as depressive and subjective symptoms were analyzed.</p> <p><b>Results:</b> At baseline, patients with coronary artery disease (CABG, off-pump, and NSCC) had lower performance than the HHC group in several cognitive domains. By 3 months, all groups had improved. From 3 to 12 months, there were minimal intrasubject changes for all groups. No consistent differences between the CABG and off-pump patients were observed.</p> <p><b>Conclusions:</b> Compared with heart healthy controls (HHC), the groups with coronary artery disease had lower cognitive test scores at baseline. There was no evidence that the cognitive test performance of coronary artery bypass grafting (CABG) patients differed from that of control groups with coronary artery disease over a 1-year period. This study emphasizes the need for appropriate control groups for interpreting longitudinal changes in cognitive performance after CABG.</p&gt