Implementation of a Modified Early Screening for Discharge Tool to Optimize Case Manager Efficiency and Impact Length of Stay.

PURPOSE OF STUDY: The postacute landscape has been challenged since the onset of the COVID-19 pandemic by staffing shortages and a decline in postacute bed availability. As a result, patients in acute care hospitals are experiencing longer lengths of stay (LOS) and case managers (CMs) are managing increasingly complex discharge plans. This project involved the design and implementation of a modified Early Screen for Discharge Planning (ESDP) tool to support prioritizing patients with complex discharge needs, with the primary outcome of decreasing LOS. PRIMARY PRACTICE SETTING: The project took place in a community teaching hospital, part of a large academic health system in the Northeast, United States. METHODOLOGY AND PARTICIPANTS: The project was designed as a prospective controlled study (between September 1 and November 30, 2021) with defined intervention and control cohorts, involving a modified ESDP electronic health record-based score including self-rated walking limitation, age, prior living status, and mobility level of assist. A modified ESDP score of 10 and greater indicated that patients would benefit from ongoing CM support, whereas those with an ESDP score of less than 10 were unlikely to have discharge planning needs. Participants were adult patients on medical and surgical inpatient units. RESULTS: The project included 718 patients, 376 and 342 in the intervention and control cohorts, respectively. The modified ESDP performed comparably with the standard ESDP (14% discrepancy, with all patients appropriately identified for CM services). Implementation of the modified ESDP led to 53.5% of patients screening out of CM services, thereby increasing the time CMs were able to spend on complex discharge planning and was associated with a trend in LOS reduction (0.55 days). IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The findings of this project demonstrate that implementation of a modified ESDP can improve CM efficiency and improve hospital throughput. Given the unprecedented capacity challenges in both the acute and postacute settings, there is a need to implement CM workflow strategies that will optimize the effectiveness of critical resources, while ensuring that patients' complex discharge needs are met.

Parallel randomized controlled feasibility trials of the "Active Brains" digital intervention to protect cognitive health in adults aged 60-85.

Introduction: Multidomain interventions to address modifiable risk factors for dementia are promising, but require more cost-effective, scalable delivery. This study investigated the feasibility of the "Active Brains" digital behavior change intervention and its trial procedures. Materials and methods: Active Brains aims to reduce cognitive decline by promoting physical activity, healthy eating, and online cognitive training. We conducted 12-month parallel-design randomized controlled feasibility trials of "Active Brains" amongst "lower cognitive scoring" (n = 180) and "higher cognitive scoring" (n = 180) adults aged 60-85. Results: We collected 67.2 and 76.1% of our 12-month primary outcome (Baddeley verbal reasoning task) data for the "lower cognitive score" and "higher cognitive score" groups, respectively. Usage of "Active Brains" indicated overall feasibility and satisfactory engagement with the physical activity intervention content (which did not require sustained online engagement), but engagement with online cognitive training was limited. Uptake of the additional brief telephone support appeared to be higher in the "lower cognitive score" trial. Preliminary descriptive trends in the primary outcome data might indicate a protective effect of Active Brains against cognitive decline, but further investigation in fully-powered trials is required to answer this definitively. Discussion: Whilst initial uptake and engagement with the online intervention was modest, it was in line with typical usage of other digital behavior change interventions, and early indications from the descriptive analysis of the primary outcome and behavioral data suggest that further exploration of the potential protective benefits of Active Brains are warranted. The study also identified minor modifications to procedures, particularly to improve online primary-outcome completion. Further investigation of Active Brains will now seek to determine its efficacy in protecting cognitive performance amongst adults aged 60-85 with varied levels of existing cognitive performance.

Accuracy of ultrasound in the estimation of customised birth weight in a public hospital service.

INTRODUCTION: Studies have shown that ultrasound estimated foetal weight (EFW) in small for gestational age (SGA) babies tends to be less-accurate when compared to appropriate (AGA) and large (LGA) for gestational age babies. We aimed to analyse the accuracy of ultrasound EFW overall, and by customised birth weight centile category (severe SGA, SGA, AGA, LGA). Also, the accuracy of estimating the centile category using calculated customised EFW centiles. METHODS: We performed a retrospective study of pregnant women between 20-43 weeks gestation who underwent ultrasound within 7 days of delivery at a large tertiary maternity unit between January 2018 and December 2020. Stillbirths, major foetal anomalies and multiple pregnancies were excluded. The EFW and birth weight were compared, and an accurate estimate defined as ≤15% difference. The customised EFW and birth weight centiles were calculated and used to analyse the accuracy of category prediction. RESULTS: Of 2061 foetuses included, 92% (n = 1902) were born weighing within 15% of their EFW. Accuracy was not affected by maternal BMI, ethnicity, parity or gestation. 87% of SGA babies were within 15% of their EFW. Ultrasound sensitivity for SGA was 51% (95% CI: 46-55%). The specificity and positive predictive values were 97% (95% CI: 96-98%) and 87% (95% CI: 82-90%) respectively. CONCLUSION: The accuracy of Ultrasound EFW overall is good, however, is reduced in SGA babies whose EFW and birth weight centile categories tended to be overestimated. The high specificity for SGA supports monitoring with a lowered threshold to intervene in pregnancies identified by ultrasound as SGA.

Accuracy of ultrasound in estimating fetal weight in New Zealand.

INTRODUCTION: Ultrasound estimation of fetal weight is an important factor guiding antenatal management. We aimed to review the accuracy of ultrasound in predicting fetal weight and birthweight category and identify influencing factors. METHODS: We performed a retrospective study of term pregnant women who underwent ultrasound within 7 days of delivery at National Women's Health between January 2019 and January 2020. Stillbirths, major fetal anomalies and multiple pregnancies were excluded. Estimated fetal weight (EFW) was calculated using Hadlock formula and compared with birthweights. We evaluated change in weight categories due to these errors. RESULTS: Of 560 fetuses included, three quarters (n = 425, 76%) of EFWs were within 10% of birthweight. 135 fetuses had EFWs either less than 90% (n = 19) or greater than 110% (n = 116). Fetuses with EFW < 90% had longer times between scanning and delivery, lower EFW and higher maternal BMI. Fetuses with EFW > 110% were associated with higher EFW, later gestational age and older maternal age. US incorrectly estimated 71 (12.7%) fetal birthweight categories. Underestimated weight category (8.9%) was associated with higher maternal BMI. DISCUSSION: Inaccurate EFWs were more common at the extremes of fetal weight. A significant association was underestimation birthweight in mothers with increased BMI, who are at increased risk for perinatal and surgical complications. CONCLUSION: Our accuracy of 76% correctly predicted EFWs compares favourably with previous studies. Clinicians and sonographers should be aware of the increased risk for inaccurate categorisation of fetuses at the extremes of EFW and in mothers with increased BMI.

Involvement of the epidermal growth factor receptor in IL-13-mediated corticosteroid-resistant airway inflammation.

BACKGROUND: Effective treatment for severe asthma is a significant unmet need. While eosinophilic inflammation caused by type 2 cytokines is responsive to corticosteroid and biologic therapies, many severe asthmatics exhibit corticosteroid-unresponsive mixed granulocytic inflammation. OBJECTIVE: Here, we tested the hypothesis that the pro-allergic cytokine, IL-13, can drive both corticosteroid-sensitive and corticosteroid-resistant responses. RESULTS: By integration of in vivo and in vitro models of IL-13-driven inflammation, we identify a role for the epidermal growth factor receptor (EGFR/ERBB1) as a mediator of corticosteroid-unresponsive inflammation and bronchial hyperresponsiveness driven by IL-13. Topological data analysis using human epithelial transcriptomic data from the U-BIOPRED cohort identified severe asthma groups with features consistent with the presence of IL-13 and EGFR/ERBB activation, with involvement of distinct EGFR ligands. Our data suggest that IL-13 may play a dual role in severe asthma: on the one hand driving pathologic corticosteroid-refractory mixed granulocytic inflammation, but on the other hand underpinning beneficial epithelial repair responses, which may confound responses in clinical trials. CONCLUSION AND CLINICAL RELEVANCE: Detailed dissection of those molecular pathways that are downstream of IL-13 and utilize the ERBB receptor and ligand family to drive corticosteroid-refractory inflammation should enhance the development of new treatments that target this sub-phenotype(s) of severe asthma, where there is an unmet need.

Previvor: An Oncology Nurse's Story of Cancer Risk Reduction Through Genetic Testing.

My mother was diagnosed with triple-negative breast cancer in 1998 at age 48. Her younger sister has been diagnosed with breast cancer at age 33 but ultimately died of ovarian cancer at age 47. Her mother died of ovarian cancer at age 47. I knew my fate. Meanwhile, as the medical world around me kept turning, the medical-surgical floor on which I worked became an oncology floor. This was not part of my plan.

Effectiveness of adjunctive, personalised psychosocial intervention for non-response to opioid agonist treatment: Study protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Opioid use disorder (OUD) is a debilitating and relapsing psychiatric disorder; opioid agonist therapy (OAT) is the front-line, evidence-supported treatment. A substantial number of patients relapse or continue to use heroin or other illicit drugs during OAT. There is considerable heterogeneity in the OAT-resistant sub-population, with many behavioural moderators of treatment response. We have developed a personalised psychosocial intervention (PSI) targeting these individuals. A formulation-guided assessment is linked to a toolkit of motivational, cognitive/behavioural and social support techniques. Change methods have been adapted from evidence-supported psychological therapies and are idiosyncratically tailored to the need and response. METHODS: In this single-centre, 18-week, parallel group, pragmatic randomised clinical trial, we will determine the clinical and cost-effectiveness of the PSI as an adjunctive intervention during OAT, in comparison to opioid agonist treatment-as-usual. We plan to recruit 368 adults. The primary outcome measure is the proportion of participants categorised as 'responders' at the end of the intervention (defined as self-reported abstinence from heroin and cocaine with no positive biological drug tests during the 28days prior to the endpoint). Secondary outcomes include: percentage of days abstinent from heroin and cocaine in the 28days before follow-up; treatment retention; therapy compliance; health and social functioning; exploratory genetic biomarkers; and analyses of treatment moderation and mediation. CONCLUSIONS: This pragmatic controlled trial determines the effectiveness and cost-effectiveness of a personalised PSI for non-responding patients during OAT. Our intervention applies motivational, cognitive/behavioural and social support techniques adapted from evidence-based therapies. Findings will inform stratified delivery of OAT.

Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life.

Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma.

An internet-delivered handwashing intervention to modify influenza-like illness and respiratory infection transmission (PRIMIT): a primary care randomised trial.

BACKGROUND: Handwashing to prevent transmission of respiratory tract infections (RTIs) has been widely advocated, especially during the H1N1 pandemic. However, the role of handwashing is debated, and no good randomised evidence exists among adults in non-deprived settings. We aimed to assess whether an internet-delivered intervention to modify handwashing would reduce the number of RTIs among adults and their household members. METHODS: We recruited individuals sharing a household by mailed invitation through general practices in England. After consent, participants were randomised online by an automated computer-generated random number programme to receive either no access or access to a bespoke automated web-based intervention that maximised handwashing intention, monitored handwashing behaviour, provided tailored feedback, reinforced helpful attitudes and norms, and addressed negative beliefs. We enrolled participants into an additional cohort (randomised to receive intervention or no intervention) to assess whether the baseline questionnaire on handwashing would affect handwashing behaviour. Participants were not masked to intervention allocation, but statistical analysis commands were constructed masked to group. The primary outcome was number of episodes of RTIs in index participants in a modified intention-to-treat population of randomly assigned participants who completed follow-up at 16 weeks. This trial is registered with the ISRCTN registry, number ISRCTN75058295. FINDINGS: Across three winters between Jan 17, 2011, and March 31, 2013, we enrolled 20,066 participants and randomly assigned them to receive intervention (n=10,040) or no intervention (n=10,026). 16,908 (84%) participants were followed up with the 16 week questionnaire (8241 index participants in intervention group and 8667 in control group). After 16 weeks, 4242 individuals (51%) in the intervention group reported one or more episodes of RTI compared with 5135 (59%) in the control group (multivariate risk ratio 0·86, 95% CI 0·83-0·89; p<0·0001). The intervention reduced transmission of RTIs (reported within 1 week of another household member) both to and from the index person. We noted a slight increase in minor self-reported skin irritation (231 [4%] of 5429 in intervention group vs 79 [1%] of 6087 in control group) and no reported serious adverse events. INTERPRETATION: In non-pandemic years, an effective internet intervention designed to increase handwashing could have an important effect in reduction of infection transmission. In view of the heightened concern during a pandemic and the likely role of the internet in access to advice, the intervention also has potential for effective implementation during a pandemic. FUNDING: Medical Research Council.

Randomised controlled trial of a brief intervention targeting predominantly non-verbal communication in general practice consultations.

BACKGROUND: The impact of changing non-verbal consultation behaviours is unknown. AIM: To assess brief physician training on improving predominantly non-verbal communication. DESIGN AND SETTING: Cluster randomised parallel group trial among adults aged ≥16 years attending general practices close to the study coordinating centres in Southampton. METHOD: Sixteen GPs were randomised to no training, or training consisting of a brief presentation of behaviours identified from a prior study (acronym KEPe Warm: demonstrating Knowledge of the patient; Encouraging [back-channelling by saying 'hmm', for example]; Physically engaging [touch, gestures, slight lean]; Warm-up: cool/professional initially, warming up, avoiding distancing or non-verbal cut-offs at the end of the consultation); and encouragement to reflect on videos of their consultation. Outcomes were the Medical Interview Satisfaction Scale (MISS) mean item score (1-7) and patients' perceptions of other domains of communication. RESULTS: Intervention participants scored higher MISS overall (0.23, 95% confidence interval [CI] = 0.06 to 0.41), with the largest changes in the distress-relief and perceived relationship subscales. Significant improvement occurred in perceived communication/partnership (0.29, 95% CI = 0.09 to 0.49) and health promotion (0.26, 95% CI = 0.05 to 0.46). Non-significant improvements occurred in perceptions of a personal relationship, a positive approach, and understanding the effects of the illness on life. CONCLUSION: Brief training of GPs in predominantly non-verbal communication in the consultation and reflection on consultation videotapes improves patients' perceptions of satisfaction, distress, a partnership approach, and health promotion.

Verbal and non-verbal behaviour and patient perception of communication in primary care: an observational study.

BACKGROUND: Few studies have assessed the importance of a broad range of verbal and non-verbal consultation behaviours. AIM: To explore the relationship of observer ratings of behaviours of videotaped consultations with patients' perceptions. DESIGN AND SETTING: Observational study in general practices close to Southampton, Southern England. METHOD: Verbal and non-verbal behaviour was rated by independent observers blind to outcome. Patients competed the Medical Interview Satisfaction Scale (MISS; primary outcome) and questionnaires addressing other communication domains. RESULTS: In total, 275/360 consultations from 25 GPs had useable videotapes. Higher MISS scores were associated with slight forward lean (an 0.02 increase for each degree of lean, 95% confidence interval [CI] = 0.002 to 0.03), the number of gestures (0.08, 95% CI = 0.01 to 0.15), 'back-channelling' (for example, saying 'mmm') (0.11, 95% CI = 0.02 to 0.2), and social talk (0.29, 95% CI = 0.4 to 0.54). Starting the consultation with professional coolness ('aloof') was helpful and optimism unhelpful. Finishing with non-verbal 'cut-offs' (for example, looking away), being professionally cool ('aloof'), or patronising, ('infantilising') resulted in poorer ratings. Physical contact was also important, but not traditional verbal communication. CONCLUSION: These exploratory results require confirmation, but suggest that patients may be responding to several non-verbal behaviours and non-specific verbal behaviours, such as social talk and back-channelling, more than traditional verbal behaviours. A changing consultation dynamic may also help, from professional 'coolness' at the beginning of the consultation to becoming warmer and avoiding non-verbal cut-offs at the end.

Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial.

OBJECTIVE: To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections. DESIGN: Open pragmatic parallel group factorial randomised controlled trial. SETTING: Primary care in United Kingdom. PARTICIPANTS: Patients aged ≥ 3 with acute respiratory tract infections. INTERVENTION: 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation). OUTCOMES: Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations. RESULTS: Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval -0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, -0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5 °C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen -0.40, -0.78 to -0.01; combination -0.47; -0.84 to -0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: -0.47, -0.76 to -0.18; combination: -0.04, -0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients (2%) who returned full diaries, but no reconsultations with scalding were documented. CONCLUSION: Overall advice to use steam inhalation, or ibuprofen rather than paracetamol, does not help control symptoms in patients with acute respiratory tract infections and must be balanced against the possible progression of symptoms during the next month for a minority of patients. Advice to use ibuprofen might help short term control of symptoms in those with chest infections and in children. TRIAL REGISTRATION: ISRCTN 38551726.

PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A ß-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat.

OBJECTIVE: To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. DESIGN: Diagnostic cohort. SETTING: UK general practices. PARTICIPANTS: Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. MAIN OUTCOME: Predictors of the presence of Lancefield A/C/G streptococci. RESULTS: The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. CONCLUSIONS: Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci.

Clinical score and rapid antigen detection test to guide antibiotic use for sore throats: randomised controlled trial of PRISM (primary care streptococcal management).

OBJECTIVE: To determine the effect of clinical scores that predict streptococcal infection or rapid streptococcal antigen detection tests compared with delayed antibiotic prescribing. DESIGN: Open adaptive pragmatic parallel group randomised controlled trial. SETTING: Primary care in United Kingdom. PATIENTS: Patients aged ≥ 3 with acute sore throat. INTERVENTION: An internet programme randomised patients to targeted antibiotic use according to: delayed antibiotics (the comparator group for analyses), clinical score, or antigen test used according to clinical score. During the trial a preliminary streptococcal score (score 1, n=1129) was replaced by a more consistent score (score 2, n=631; features: fever during previous 24 hours; purulence; attends rapidly (within three days after onset of symptoms); inflamed tonsils; no cough/coryza (acronym FeverPAIN). OUTCOMES: Symptom severity reported by patients on a 7 point Likert scale (mean severity of sore throat/difficulty swallowing for days two to four after the consultation (primary outcome)), duration of symptoms, use of antibiotics. RESULTS: For score 1 there were no significant differences between groups. For score 2, symptom severity was documented in 80% (168/207 (81%) in delayed antibiotics group; 168/211 (80%) in clinical score group; 166/213 (78%) in antigen test group). Reported severity of symptoms was lower in the clinical score group (-0.33, 95% confidence interval -0.64 to -0.02; P=0.04), equivalent to one in three rating sore throat a slight versus moderate problem, with a similar reduction for the antigen test group (-0.30, -0.61 to -0.00; P=0.05). Symptoms rated moderately bad or worse resolved significantly faster in the clinical score group (hazard ratio 1.30, 95% confidence interval 1.03 to 1.63) but not the antigen test group (1.11, 0.88 to 1.40). In the delayed antibiotics group, 75/164 (46%) used antibiotics. Use of antibiotics in the clinical score group (60/161) was 29% lower (adjusted risk ratio 0.71, 95% confidence interval 0.50 to 0.95; P=0.02) and in the antigen test group (58/164) was 27% lower (0.73, 0.52 to 0.98; P=0.03). There were no significant differences in complications or reconsultations. CONCLUSION: Targeted use of antibiotics for acute sore throat with a clinical score improves reported symptoms and reduces antibiotic use. Antigen tests used according to a clinical score provide similar benefits but with no clear advantages over a clinical score alone. TRIAL REGISTRATION: ISRCTN32027234.

Depressive disorders during weaning from prolonged mechanical ventilation.

PURPOSE: Patients who require mechanical ventilation are at risk of emotional stress because of total dependence on a machine for breathing. The stress may negatively impact ventilator weaning and survival. The purpose of this study was to determine whether depressive disorders in patients being weaned from prolonged mechanical ventilation are linked to weaning failure and decreased survival. METHODS: A prospective study of 478 consecutive patients transferred to a long-term acute care hospital for weaning from prolonged ventilation was undertaken. A clinical psychologist conducted a psychiatric interview to assess for the presence of depressive disorders. RESULTS: Of the 478 patients, 142 had persistent coma or delirium and were unable to be evaluated for depressive disorders. Of the remaining 336 patients, 142 (42%) were diagnosed with depressive disorders. In multivariate analysis, co-morbidity score [odds ratio (OR), 1.23; P = 0.007], functional dependence before the acute illness (OR, 1.70, P = 0.03) and history of psychiatric disorders (OR, 3.04, P = 0.0001) were independent predictors of depressive disorders. The rate of weaning failure was higher in patients with depressive disorders than in those without such disorders (61 vs. 33%, P = 0.0001), as was mortality (24 vs. 10%, P = 0.0008). The presence of depressive disorders was independently associated with mortality (OR, 4.3; P = 0.0002); age (OR, 1.06; P = 0.001) and co-morbidity score (OR, 1.24; P = 0.02) also predicted mortality. CONCLUSION: Depressive disorders were diagnosed in 42% of patients who were being weaned from prolonged ventilation. Patients with depressive disorders were more likely to experience weaning failure and death.

High diversity in functional properties of melanocortin 1 receptor (MC1R) in divergent primate species is more strongly associated with phylogeny than coat color.

We have characterized the biochemical function of the melanocortin 1 receptor (MC1R), a critical regulator of melanin synthesis, from 9 phylogenetically diverse primate species with varying coat colors. There is substantial diversity in melanocyte-stimulating hormone (MSH) binding affinity and basal levels of activity in the cloned MC1Rs. MSH binding was lost independently in lemur and New World monkey lineages, whereas high basal levels of MC1R activity occur in lemurs and some New World monkeys and Old World monkeys. Highest levels of basal activity were found in the MC1R of ruffed lemurs, which have the E94K mutation that leads to constitutive activation in other species. In 3 species (2 lemurs and the howler monkey), we report the novel finding that binding and inhibition of MC1R by agouti signaling protein (ASIP) can occur when MSH binding has been lost, thus enabling continuing regulation of the melanin type via ASIP expression. Together, these findings can explain the previous paradox of a predominantly pheomelanic coat in the red ruffed lemur (Varecia rubra). The presence of a functional, MSH-responsive MC1R in orangutan demonstrates that the mechanism of red hair generation in this ape is different from the prevalent mechanism in European human populations. Overall, we have found unexpected diversity in MC1R function among primates and show that the evolution of the regulatory control of MC1R activity occurs by independent variation of 3 distinct mechanisms: basal MC1R activity, MSH binding and activation, and ASIP binding and inhibition. This diversity of function is broadly associated with primate phylogeny and does not have a simple relation to coat color phenotype within primate clades.

Investigation of the role of the agouti signaling protein gene (ASIP) in coat color evolution in primates.

We investigated variation in the gene encoding the agouti signaling protein (ASIP) in relation to coat color evolution in primates. We found little evidence that mutations in the coding region of ASIP have been involved in color changes among closely related primate species. Among many closely related species with differing coat color, the coding region of ASIP was identical. In two cases (Sulawesi macaque and black lion tamarin) where species with almost completely black coat color had derived point mutations in exon 4 of the ASIP coding sequence, the same mutations did not alter coloration in other mammals and so probably do not affect ASIP function. Evolutionary reconstructions of two key phenotypes that are typically related to ASIP function--transverse phaeomelanin bands on hairs and pale ventral coloration--showed that these usually evolved concurrently, suggesting that loci acting downstream of ASIP may be involved. Analysis of dN/dS ratios revealed a likely change in functional constraint on ASIP following loss of agouti-banded hairs + pale ventral coloration, particularly in catarrhine primates (humans, apes, and Old World monkeys). Together with previous results on a lack of association of coat color with MC1R variation, these results suggest that other loci probably have an important role in primate coat color evolution.

Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial.

CONTEXT: Acute lower respiratory tract infection is the most common condition treated in primary care. Many physicians still prescribe antibiotics; however, systematic reviews of the use of antibiotics are small and have diverse conclusions. OBJECTIVE: To estimate the effectiveness of 3 prescribing strategies and an information leaflet for acute lower respiratory tract infection. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial conducted from August 18, 1998, to July 30, 2003, of 807 patients presenting in a primary care setting with acute uncomplicated lower respiratory tract infection. Patients were assigned to 1 of 6 groups by a factorial design: leaflet or no leaflet and 1 of 3 antibiotic groups (immediate antibiotics, no offer of antibiotics, and delayed antibiotics). INTERVENTION: Three strategies, immediate antibiotics (n = 262), a delayed antibiotic prescription (n = 272), and no offer of antibiotics (n = 273), were prescribed. Approximately half of each group received an information leaflet (129 for immediate antibiotics, 136 for delayed antibiotic prescription, and 140 for no antibiotics). MAIN OUTCOME MEASURES: Symptom duration and severity. RESULTS: A total of 562 patients (70%) returned complete diaries and 78 (10%) provided information about both symptom duration and severity. Cough rated at least "a slight problem" lasted a mean of 11.7 days (25% of patients had a cough lasting > or =17 days). An information leaflet had no effect on the main outcomes. Compared with no offer of antibiotics, other strategies did not alter cough duration (delayed, 0.75 days; 95% confidence intervals [CI], -0.37 to 1.88; immediate, 0.11 days; 95% CI, -1.01 to 1.24) or other primary outcomes. Compared with the immediate antibiotic group, slightly fewer patients in the delayed and control groups used antibiotics (96%, 20%, and 16%, respectively; P<.001), fewer patients were "very satisfied" (86%, 77%, and 72%, respectively; P = .005), and fewer patients believed in the effectiveness of antibiotics (75%, 40%, and 47%, respectively; P<.001). There were lower reattendances within a month with antibiotics (mean attendances for no antibiotics, 0.19; delayed, 0.12; and immediate, 0.11; P = .04) and higher attendance with a leaflet (mean attendances for no leaflet, 0.11; and leaflet, 0.17; P = .02). CONCLUSION: No offer or a delayed offer of antibiotics for acute uncomplicated lower respiratory tract infection is acceptable, associated with little difference in symptom resolution, and is likely to considerably reduce antibiotic use and beliefs in the effectiveness of antibiotics.