Efficacy and safety of lumacaftor/ivacaftor combination therapy in patients with cystic fibrosis homozygous for Phe508del CFTR by pulmonary function subgroup

Background Lumacaftor/ivacaftor combination therapy demonstrated clinical benefits inpatients with cystic fibrosis homozygous for the Phe508del CFTR mutation.Pretreatment lung function is a confounding factor that potentially impacts the efficacyand safety of lumacaftor/ivacaftor therapy. Methods Two multinational, randomised, double-blind, placebo-controlled, parallelgroupPhase 3 studies randomised patients to receive placebo or lumacaftor (600 mgonce daily [qd] or 400 mg every 12 hours [q12h]) in combination with ivacaftor (250 mgq12h) for 24 weeks. Prespecified analyses of pooled efficacy and safety data by lungfunction, as measured by percent predicted forced expiratory volume in 1 second(ppFEV1), were performed for patients with baseline ppFEV1 <40 (n=81) and ≥40(n=1016) and screening ppFEV1 <70 (n=730) and ≥70 (n=342). These studies wereregistered with ClinicalTrials.gov (NCT01807923 and NCT01807949). Findings The studies were conducted from April 2013 through April 2014.Improvements in the primary endpoint, absolute change from baseline at week 24 inppFEV1, were observed with both lumacaftor/ivacaftor doses in the subgroup withbaseline ppFEV1 <40 (least-squares mean difference versus placebo was 3∙7 and 3.3percentage points for lumacaftor 600 mg qd/ivacaftor 250 mg q12h and lumacaftor 400mg q12h/ivacaftor 250 mg q12h, respectively [p<0∙05] and in the subgroup with baselineppFEV1 ≥40 (3∙3 and 2∙8 percentage points, respectively [p<0∙001]). Similar absoluteimprovements versus placebo in ppFEV1 were observed in subgroups with screening 4ppFEV1 <70 (3∙3 and 3∙3 percentage points for lumacaftor 600 mg qd/ivacaftor 250 mgq12h and lumacaftor 400 mg q12h/ivacaftor 250 mg q12h, respectively [p<0∙001]) and≥70 (3∙3 and 1∙9 percentage points, respectively [p=0.002] and [p=0∙079]). Increases inBMI and reduction in number of pulmonary exacerbation events were observed in bothLUM/IVA dose groups vs placebo across all lung function subgroups. Treatment wasgenerally well tolerated, although the incidence of some respiratory adverse events washigher with active treatment than with placebo. Interpretation Lumacaftor/ivacaftor combination therapy benefits patients homozygousfor Phe508del CFTR who have varying degrees of lung function impairment. Funding Vertex Pharmaceuticals Incorporated.

Care planning for aggression management in a specialist secure mental health service: user involvement

This paper describes an audit of prevention and management of violence and aggression care plans and incident reporting forms which aimed to: (i) report the compliance rate of completion of care plans; (ii) identify the extent to which patients contribute to and agree with their care plan; (iii) describe de-escalation methods documented in care plans; and (iv) ascertain the extent to which the de-escalation methods described in the care plan are recorded as having been attempted in the event of an incident. Care plans and incident report forms were examined for all patients in men's and women's mental health care pathways who were involved in aggressive incidents between May and October 2012. In total, 539 incidents were examined, involving 147 patients and 121 care plans. There was no care plan in place at the time of 151 incidents giving a compliance rate of 72%. It was documented that 40% of patients had contributed to their care plans. Thematic analysis of de-escalation methods documented in the care plans revealed five de-escalation themes: staff interventions, interactions, space/quiet, activities and patient strategies/skills. A sixth category, coercive strategies, was also documented. Evidence of adherence to de-escalation elements of the care plan was documented in 58% of incidents. The reasons for the low compliance rate and very low documentation of patient involvement need further investigation. The inclusion of coercive strategies within de-escalation documentation suggests that some staff fundamentally misunderstand de-escalation.

An epidemiological surveillance network of lumbar disc surgery to help prevention of and compensation for low back pain

International audience

Anthropometric characteristics and the burden of altered nutritional status among neuropsychiatric patients at Zomba Mental Hospital in Zomba, Malawi

Objective To determine the prevalence of overnutrition and undernutrition among neuropsychiatric inpatients and outpatients at Zomba Mental Hospital in Zomba, Malawi. Methods In this analytical cross-sectional study (n = 239), data were collected from psychiatric patients who were either inpatients (n = 181) or outpatients (n = 58) at Zomba Mental Hospital, which is the largest mental health facility in Malawi. Information was collected about patient demographics, anthropometric data, dietary information, and tobacco and alcohol use, among other variables. Data were entered and analysed in SPSS 16.0 (SPSS Inc., Chicago, IL, USA). Means were generated and compared between male and female patients, and between inpatients and outpatients. Results The study recruited 158 male and 81 female patients, with mean ages of 31.24 ± 11.85 years and 33.08 ± 15.18 years (p = 0.328), respectively. Male patients were significantly taller (165.27 ± 7.25 cm) than female patients (155.30 ± 6.56 cm) (p < 0.001); were significantly heavier than females (60.02 ± 10.56 kg versus 55.64 ± 10.53 kg); and had a significantly lower mean body mass index (BMI) than females (21.87 ± 3.21 vs. 23.01 ± 3.78) (p = 0.016). Overweight and obese patients comprised 17.6% of the participants, and 8.8% were underweight. There were no significant differences in the prevalence of overweight, obesity, and underweight between male and female participants, or between inpatients and outpatients. Conclusion Our study—the first one of its kind in Malawi—characterised the anthropometry of neuropsychiatric patients at a major metal health facility in Malawi, and has shown a high proportion of overweight patients and a notable presence of underweight patients among them. Being overweight or obese is a risk factor for metabolic disorders. Being underweight may aggravate mental illness or disturb the effect of medication. There is need, therefore, to include nutrition screening and therapeutic or supplementary feeding as part of a comprehensive care and treatment plan for neuropsychiatric patients.

Prevalence of AmpC β-lactamase among Gram-negative bacteria recovered from clinical specimens in Benin City, Nigeria

Purpose: Infections caused by AmpC-positive bacteria results in high patient morbidity and mortality making their detection clinically important as they cannot be detected in routine susceptibility testing. This study aim to determine the prevalence of AmpC β-lactamase among Gram negative bacteria recovered from clinical specimens in Benin City, Nigeria. Methods: A total of 256 consecutive and non-repetitive Gram negative bacteria were recovered from various clinical specimens. The prevalence of AmpC β-lactamase was determined using a combination of disc antagonism test and cefoxitin-cloxacillin inhibition test. Disc susceptibility test was performed on all isolates using standard techniques. Results: Cefoxitin-cloxacillin inhibition test detected more AmpC β-lactamase than other tests. The prevalence of AmpC β-lactamase did not differ significantly between both genders and between inpatients and out-patients (p>0.05). Isolates recovered from sputum had significantly higher prevalence of AmpC β-lactamase producers compared with isolates from other clinical specimens (p=0.0484). The prevalence of AmpC production was significantly higher among isolates of Pseudomonas aeruginosa than other isolates (p = 0.0085). Isolates that produced AmpC β-lactamase were more susceptible to the test cephalosoprins. Conclusion: An overall prevalence of AmpC β-lactamase (15.23 %) was observed in this study. Pseudomonas aeruginosa was the most prevalent producer of AmpC enzymes. Prudent use of antibiotics is advocated.

Structured professional judgement approach to risk assessment: generalisability across patient groups for the prediction of adverse outcomes in secure mental health care

This is a redacted version of the the final thesis. Copyright material has been removed to comply with UK Copyright Law.

Cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. Due to ageing of the general population and improved survival from cardiac disease the prevalence of heart failure is rising. Despite the fact that the majority of patients with heart failure are aged over 65 years old, many with multiple co-morbidities, the association between cognitive impairment and heart failure has received relatively little research interest compared to other aspects of cardiac disease. The presence of concomitant cognitive impairment has implications for the management of patients with heart failure in the community. There are many evidence based pharmacological therapies used in heart failure management which obviously rely on patient education regarding compliance. Also central to the treatment of heart failure is patient self-monitoring for signs indicative of clinical deterioration which may prompt them to seek medical assistance or initiate a therapeutic intervention e.g. taking additional diuretic. Adherence and self-management may be jeopardised by cognitive impairment. Formal diagnosis of cognitive impairment requires evidence of abnormalities on neuropsychological testing (typically a result ≥1.5 standard deviation below the age-standardised mean) in at least one cognitive domain. Cognitive impairment is associated with an increased risk of dementia and people with mild cognitive impairment develop dementia at a rate of 10-15% per year, compared with a rate of 1-2% per year in healthy controls.1 Cognitive impairment has been reported in a variety of cardiovascular disorders. It is well documented among patients with hypertension, atrial fibrillation and coronary artery disease, especially after coronary artery bypass grafting. This background is relevant to the study of patients with heart failure as many, if not most, have a history of one or more of these co-morbidities. A systematic review of the literature to date has shown a wide variation in the reported prevalence of cognitive impairment in heart failure. This range in variation probably reflects small study sample sizes, differences in the heart failure populations studied (inpatients versus outpatients), neuropsychological tests employed and threshold values used to define cognitive impairment. The main aim of this study was to identify the prevalence of cognitive impairment in a representative sample of heart failure patients and to examine whether this association was due to heart failure per se rather than the common cardiovascular co-morbidities that often accompany it such as atherosclerosis and atrial fibrillation. Of the 817 potential participants screened, 344 were included in this study. The study cohort included 196 patients with HF, 61 patients with ischaemic heart disease and no HF and 87 healthy control participants. The HF cohort consisted of 70 patients with HF and coronary artery disease in sinus rhythm, 51 patients with no coronary artery disease in sinus rhythm and 75 patients with HF and atrial fibrillation. All patients with HF had evidence of HF-REF with a LVEF <45% on transthoracic echocardiography. The majority of the cohort was male and elderly. HF patients with AF were more likely to have multiple co-morbidities. Patients recruited from cardiac rehabilitation clinics had proven coronary artery disease, no clinical HF and a LVEF >55%. The ischaemic heart disease group were relatively well matched to healthy controls who had no previous diagnosis of any chronic illness, prescribed no regular medication and also had a LVEF >55%. All participants underwent the same baseline investigations and there were no obvious differences in baseline demographics between each of the cohorts. All 344 participants attended for 2 study visits. Baseline investigations including physiological measurements, electrocardiography, echocardiography and laboratory testing were all completed at the initial screening visit. Participants were then invited to attend their second study visit within 10 days of the screening visit. 342 participants completed all neuropsychological assessments (2 participants failed to complete 1 questionnaire). A full comprehensive battery of neuropsychological assessment tools were administered in the 90 minute study visit. These included three global cognitive screening assessment tools (mini mental state examination, Montreal cognitive assessment tool and the repeatable battery for the assessment of neuropsychological status) and additional measures of executive function (an area we believe has been understudied to date). In total there were 9 cognitive tests performed. These were generally well tolerated. Data were also collected using quality of life questionnaires and health status measures. In addition to this, carers of the study participant were asked to complete a measure of caregiver strain and an informant questionnaire on cognitive decline. The prevalence of cognitive impairment varied significantly depending on the neuropsychological assessment tool used and cut-off value used to define cognitive impairment. Despite this, all assessment tools showed the same pattern of results with those patients with heart failure and atrial fibrillation having poorer cognitive performance than those with heart failure in sinus rhythm. Cognitive impairment was also more common in patients with cardiac disease (either coronary artery disease or heart failure) than age-, sex- and education-matched healthy controls, even after adjustment for common vascular risk factors.

Descripción del análisis microbológico realizado mediante maldi-tof en muestras de la fundación santa fe de Bogotá.

Introducción: La rápida detección e identificación bacteriana es fundamental para el manejo de los pacientes críticos que presentan una patología infecciosa, esto requiere de métodos rápidos para el inicio de un correcto tratamiento. En Colombia se usan pruebas microbiología convencional. No hay estudios de espectrofotometría de masas en análisis de muestras de pacientes críticos en Colombia. Objetivo general: Describir la experiencia del análisis microbiológico mediante la tecnología MALDI-TOF MS en muestras tomadas en la Fundación Santa Fe de Bogotá. Materiales y Métodos: Entre junio y julio de 2013, se analizaron 147 aislamientos bacterianos de muestras clínicas, las cuales fueron procesadas previamente por medio del sistema VITEK II. Los aislamientos correspondieron a 88 hemocultivos (60%), 28 urocultivos (19%), y otros cultivos 31 (21%). Resultados: Se obtuvieron 147 aislamientos con identificación adecuada a nivel de género y/o especie así: en el 88.4% (130 muestras) a nivel de género y especie, con una concordancia del 100% comparado con el sistema VITEK II. El porcentaje de identificación fue de 66% en el grupo de bacilos gram negativos no fermentadores, 96% en enterobacterias, 100% en gérmenes fastidiosos, 92% en cocos gram positivos, 100% bacilos gram negativos móviles y 100% en levaduras. No se encontró ninguna concordancia en bacilos gram positivos y gérmenes del genero Aggregatibacter. Conclusiones: El MALDI-TOF es una prueba rápida para la identificación microbiológica de género y especie que concuerda con los resultados obtenidos de manera convencional. Faltan estudios para hacer del MALDI-TOF MS la prueba oro en identificación de gérmenes.

Impact on hip fracture mortality after the establishment of an orthogeriatric care program in a colombian hospital

El objetivo del estudio es evaluar la mortalidad a un año en pacientes con fractura de cadera, mayores de 65 años tratados en un programa establecido de orto-geriatría. 298 se trataron de acuerdo al protocolo de orto-geriatría, se calculo la mortalidad a un año, se establecieron los predictores de mortalidad orto-geriátrico. La sobrevida anual se incremento de 80% a 89% (p = .039) durante los cuatro años de seguimiento del programa y disminuyo el riesgo de mortalidad anual postoperatorio (Hazard Ratio = 0.54, p = .049). La enfermedad cardiaca y la edad maor a 85 años fueron predictores positivos para mortalidad.

Descripción de la prevalencia del boarding en la fundación santa fe de bogotá.

Introducción: El boarding es el fenómeno que ocurre cuando existen pacientes hospitalizados en urgencias sin una cama de hospitalización a la cual trasladarse, en la literatura mundial se ha identificado como un factor que repercute en la calidad y seguridad de la atención en urgencias. Este trabajo busca describir la prevalencia de dicho fenómeno en el servicio de urgencias de la Fundación Santa fe de Bogotá Metodología: Estudio observacional de prevalencia. Se incluyeron pacientes del mes de octubre de 2015 atendidos por especialistas en medicina de emergencias de la Fundación Santa fe de Bogotá. Se tomaron datos del turno realizado (mañana, tarde y noche), y datos del servicio de urgencias para su descripción. Resultados: La mediana de ocupación por boarding en urgencias fue del 68% con un rango intercuartil de 54-75%; en términos de tiempo en minutos, la mediana fue de 1054 minutos, con un rango intercuartil de 621-1490. Existen diferencias numéricas del tiempo en minutos de acuerdo el turno (mañana: 992,77 DE 519, tarde:1584,13 DE 1000,27 noche:1304,13 DE 2126,43). Discusión: El tiempo de boarding reportado para urgencias de la Fundación Santa fe de Bogotá es comparativamente mayor al descrito en la literatura mundial, se deben explorar en estudios analíticos posteriores los factores o variables que se asocien a la presencia de este fenómeno.

Identification of a molecular signature as potential biomarker in blood of symptomatic and asymptomatic patients with carotid atherosclerosis

Background and Objectives: Carotid revascularization to prevent future vascular events is reasonable in patients with high-grade carotid stenosis. Currently, several biomarkers to predict carotid plaque development and progression have been investigated, among which microRNAs (miRs) are promising tools for the diagnosis of atherosclerosis. Methods and Results: A total of 49 participants were included in the study, divided into two main populations: Population 1 comprising symptomatic and asymptomatic inpatients, and Population 2 comprising asymptomatic outpatients. The study consisted of two main phases: a preliminary discovery phase and a validation phase, applying different techniques. MiR-profiles were performed on plasma and plaque tissue samples obtained from 4 symptomatic and 4 asymptomatic inpatients. MiRs emerging from profiling comparisons, i.e. miR-126-5p, miR-134-5p, miR-145-5p, miR-151a-5p, miR-34b, miR-451a, miR-720 and miR-1271-5p, were subjected to validation through RT-qPCR analysis in the total cohort of donors. Comparing asymptomatic and symptomatic inpatients, significant differences were reported in the expression levels of c-miRs for miR-126-5p and miR-1271-5p in blood, being more expressed in symptomatic subjects. In contrast, simultaneous evaluation of the selected miRs in plaque tissue samples did not confirm data obtained by the miR profiling, and no significant differences were observed. Using Receiver-Operating Characteristic (ROC) analysis, a circulating molecular signature (mir-126-5p, miR-1271-5p, albumin, C-reactive protein, and monocytes) was identified, allowing the distinction of the two groups in Population 1 (AUC = 0.795). Conclusions: Data emerging from this thesis suggest that c-miRs (i.e. miR-126-5p, miR-1271-5p) combined with selected haemato-biochemical parameters (albumin, C-reactive protein, and monocytes) produced a good molecular 'signature' to distinguish asymptomatic and symptomatic inpatients. C-miRs in blood do not necessarily reflect the expression levels of the same miRs in carotid plaque tissues since different mechanism can influence their expression.