LUMBAR syndrome-OEIS complex overlap: A case series and review.

We present three new and six published infants with overlapping features of LUMBAR syndrome (lower body hemangioma, urogenital anomalies, spinal cord malformations, bony deformities, anorectal/arterial anomalies and renal anomalies) and OEIS complex (omphalocele, exstrophy, imperforate anus, and spinal defects), also known as cloacal exstrophy. OEIS is included under the recently proposed umbrella coined recurrent constellations of embryonic malformations (RCEMs). The RCEMs represent a phenotypically overlapping spectrum of rare disorders of caudal dysgenesis with unknown cause but likely shared pathogenesis. It has recently been proposed that LUMBAR be considered an RCEM. This report of infants with combined features of OEIS and LUMBAR is the first to demonstrate an overlap between LUMBAR and another RCEM, which supports LUMBAR's inclusion within the RCEM spectrum.

Proposals for revised IWG 2018 hematological response criteria in patients with MDS included in clinical trials.

The heterogeneity of myelodysplastic syndromes (MDSs) has made evaluating patient response to treatment challenging. In 2006, the International Working Group (IWG) proposed a revision to previously published standardized response criteria (IWG 2000) for uniformly evaluating clinical responses in MDSs. These IWG 2006 criteria have been used prospectively in many clinical trials in MDSs, but proved challenging in several of them, especially for the evaluation of erythroid response. In this report, we provide rationale for modifications (IWG 2018) of these recommendations, mainly for "hematological improvement" criteria used for lower-risk MDSs, based on recent practical and reported experience in clinical trials. Most suggestions relate to erythroid response assessment, which are refined in an overall more stringent manner. Two major proposed changes are the differentiation between "procedures" and "criteria" for hematologic improvement-erythroid assessment and a new categorization of transfusion-burden subgroups.

Effect of body surface area and gender on wall thickness thresholds in hypertrophic cardiomyopathy.

BACKGROUND: Family screening for hypertrophic cardiomyopathy (HCM) is based on genetic testing and clinical evaluation (maximal left ventricular wall thickness (MWT) ≥15 mm, or ≥13 mm in first-degree relatives of HCM patients). The aim of this study was to assess the effect of gender and body size on diagnosis of HCM and prediction of clinical outcome. METHODS: This study includes 199 genotype-positive subjects (age 44 ± 15 years, 50% men) referred for cardiac screening. Gender-specific reference values for MWT indexed by body surface area (BSA), height and weight were derived from 147 healthy controls. Predictive accuracy of each method for HCM-related events was assessed by comparing areas under the receiver operating characteristic curves (AUC). RESULTS: Men had a higher absolute, but similar BSA- and weight-indexed MWT compared with women (14.0 ± 3.9 mm vs 11.5 ± 3.8 mm, p < 0.05; 6.8 ± 2.1 mm/m2 vs 6.6 ± 2.4 mm/m2; 0.17 ± 0.06 mm/kg vs 0.17 ± 0.06 mm/kg, both p > 0.05). Applying BSA- and weight-indexed cut-off values decreased HCM diagnoses in the study group (48% vs 42%; 48% vs 39%, both p < 0.05), reclassified subjects in the largest, lightest and heaviest tertiles (≥2.03 m2: 58% vs 45%; ≤70 kg: 37% vs 46%; ≥85 kg: 53% vs 25%, all p < 0.05) and improved predictive accuracy (AUC 0.76 [95% CI 0.69-0.82] vs 0.78 [0.72-0.85]; and vs 0.80 [0.74-0.87]; both p < 0.05). CONCLUSIONS: In genotype-positive subjects referred for family screening, differences in MWT across gender are mitigated after indexation by BSA or weight. Indexation decreases the prevalence of HCM, particularly in larger men, and improves the predictive accuracy for HCM-related events.

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

Theory analysis of the Dental Hygiene Human Needs Conceptual Model.

PURPOSE: Theories provide a structural knowing about concept relationships, practice intricacies, and intuitions and thus shape the distinct body of the profession. Capturing ways of knowing and being is essential to any professions' practice, education and research. This process defines the phenomenon of the profession - its existence or experience. Theory evaluation is a systematic criterion-based assessment of a specific theory. This study presents a theory analysis of the Dental Hygiene Human Needs Conceptual Model (DH HNCM). METHODS: Using the Walker and Avant Theory Analysis, a seven-step process, the DH HNCM, was analysed and evaluated for its meaningfulness and contribution to dental hygiene. The steps include the following: (i) investigate the origins; (ii) examine relationships of the theory's concepts; (iii) assess the logic of the theory's structure; (iv) consider the usefulness to practice; (v) judge the generalizability; (vi) evaluate the parsimony; and (vii) appraise the testability of the theory. FINDINGS: Human needs theory in nursing and Maslow's Hierarchy of Need Theory prompted this theory's development. The DH HNCM depicts four concepts based on the paradigm concepts of the profession: client, health/oral health, environment and dental hygiene actions, and includes validated eleven human needs that evolved overtime to eight. It is logical, simplistic, allows scientific predictions and testing, and provides a unique lens for the dental hygiene practitioner. With this model, dental hygienists have entered practice, knowing they enable clients to meet their human needs. CONCLUSION: For the DH HNCM, theory analysis affirmed that the model is reasonable and insightful and adds to the dental hygiene professions' epistemology and ontology.

Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

Early market access of cancer drugs in the EU.

Patient access to new cancer drugs in the EU involves centralised licensing decisions by regulators as well as reimbursement recommendations in the context of national healthcare systems. Differences in assessment criteria and evidence requirements may result in divergent decisions at central and national levels, ultimately compromising effective access to patients. Early access decisions are particularly challenging due to the limited clinical evidence available to conclude on the benefit-risk and relative (cost-) effectiveness of new high-priced cancer drugs. We describe mechanisms to accelerate approval of promising anticancer drugs that fulfil an unmet medical need, review the experience from the European Medicines Agency, compare timelines and outcomes of reimbursement decisions in major EU markets, and discuss shortcomings of the current system, ongoing initiatives, and future steps to facilitate effective early access.

Assessment of adult patients with chronic liver failure for liver transplantation in 2015: who and when?

In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease (MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future.

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation.

Cardiovascular sequelae in long-term survivors of young peoples' cancer: a linked cohort study.

BACKGROUND: We aimed to define the incidence and risk of cardiovascular late effects (LEs) identified from inpatient hospital episode statistics (HES) among long-term survivors of cancer in young people by age at diagnosis (0-14 and 15-29 years). METHODS: Records from the Yorkshire Specialist Register of Cancer in Children and Young People (1991-2006) were linked to inpatient HES data (1996-2011) to assess rates of cardiovascular LEs. Rates were compared with the general population in Yorkshire using age-sex-matched HES records for the entire region. RESULTS: Of 3247 survivors of cancer, 3.6% had at least one cardiovascular LE. Overall, cardiovascular hospitalisations for the childhood cohort were threefold higher compared with the general population, but did not differ for young adults. For young adults, increased rates were limited to pericardial disease, cardiomyopathy and heart failure, pulmonary heart disease, hypertension and conduction disorders. CONCLUSIONS: Survivors of childhood and young adult cancer remain at increased risk of cardiovascular LEs compared with the general population.

Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts.

BACKGROUND: Myelodysplastic syndromes are a diverse and common group of chronic hematologic cancers. The identification of new genetic lesions could facilitate new diagnostic and therapeutic strategies. METHODS: We used massively parallel sequencing technology to identify somatically acquired point mutations across all protein-coding exons in the genome in 9 patients with low-grade myelodysplasia. Targeted resequencing of the gene encoding RNA splicing factor 3B, subunit 1 (SF3B1), was also performed in a cohort of 2087 patients with myeloid or other cancers. RESULTS: We identified 64 point mutations in the 9 patients. Recurrent somatically acquired mutations were identified in SF3B1. Follow-up revealed SF3B1 mutations in 72 of 354 patients (20%) with myelodysplastic syndromes, with particularly high frequency among patients whose disease was characterized by ring sideroblasts (53 of 82 [65%]). The gene was also mutated in 1 to 5% of patients with a variety of other tumor types. The observed mutations were less deleterious than was expected on the basis of chance, suggesting that the mutated protein retains structural integrity with altered function. SF3B1 mutations were associated with down-regulation of key gene networks, including core mitochondrial pathways. Clinically, patients with SF3B1 mutations had fewer cytopenias and longer event-free survival than patients without SF3B1 mutations. CONCLUSIONS: Mutations in SF3B1 implicate abnormalities of messenger RNA splicing in the pathogenesis of myelodysplastic syndromes. (Funded by the Wellcome Trust and others.).

Characterization of F8 defects in haemophilia A in Pakistan: investigation of correlation between mutation type and the in vitro thrombin generation assay.

Hereditary haemophilia A is an X-linked bleeding disorder caused by mutations in the coagulation factor VIII gene (FVIII abbreviates protein, gene symbol F8). The mutation spectrum has been reported in various populations but not in Pakistan. The aims of this study were to (i) characterize F8 mutations in a large haemophilia A cohort from Pakistan and to (ii) investigate whether in vitro thrombin generation (TG) differs according to mutation type (null compared with missense) in severe haemophilia A. One hundred individuals diagnosed with haemophilia A and 100 healthy controls were recruited in Pakistan. Phenotypic measurements were re-evaluated in Cardiff; the essential regions of F8 were screened for the causative defect. A diagnosis of haemophilia A was confirmed for 92 individuals, 7 were found to have haemophilia B and 1 did not have haemophilia. The F8 defects were characterized for 80 of the 92 haemophilia A individuals and comprised point mutations, inversions (intron 22 and intron 1) and frameshifts. Point mutations (41%) were the most frequent, followed by the intron 22 inversion (20%). Thirty novel variants were identified. Comparison of in vitro TG parameters [velocity index (VI) and peak] was made between severe individuals who had a null mutation (no FVIII) and those with a missense change (dysfunctional FVIII), no significant difference was observed. The spectrum of F8 defects in Pakistan is heterogenous; VI and peak in severe haemophilia A are not influenced by whether the underlying mutation gives rise to dysfunctional FVIII or no coagulation factor at all.

Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.

Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG.

Negative pressure device used in pediatric patients with Hostile abdomen. Case series. / Dispositivo de presión negativa empleado en pacientes pediátricos con abdomen hostil: serie de casos.

INTRODUCTION: Hostile abdomen is a surgical condition characterized by loss of space between organs and structures in the abdomen. Negative pressure therapy use has been widely described in adults; the case is not the same for pediatric patients. The goal of this study is to present short-term results of negative pressure therapy use in pediatric patients with hostile abdomen due to different etiologies. MATERIAL AND METHODS: Pediatric hostile abdomen patients (< 18 years) who were treated Negative pressure therapy using ABTHERA were identified and retrospectively reviewed. RESULTS: 7 patients were included in this study. Median age was 16 (range: 9-17 yo). 5 (71.4%) were male and 2 (28.6%) females. 3 (43%) had significant past medical/surgical history (Systemic Lupus Erythematosus, complicated appendectomy and ventriculoperitoneal-shunt). The device was set at a continuous pressure ranging from -50 to -125 mmHg. Pre and post-surgical findings were reported using Bjork's classification. Devices were replaced every 4-7 days (median 5 days). Total amount of replacements was 1-4 (median 3). 5 (71.4%) patients required invasive mechanical ventilation during use of Negative pressure therapy based on clinical status. 4 (57%) patients received enteral nutrition. 1 (14%) patient required re-intervention posterior to definitive closure due to retroperitoneal abscess development. Outcome, evaluated by (oral tolerance, bowel movement and absence of pain), was favorable in all patients. CONCLUSION: Negative pressure therapy devices generate favorable results in hostile abdomen in pediatric population but further information is needed to assess pressure settings and device replacement frequency.

INTRODUCCION: El abdomen hostil es una patología quirúrgica caracterizada por una pérdida de espacio entre los órganos y estructuras del abdomen. La terapia de presión negativa se ha descrito de manera extensa en adultos, pero no así en pacientes pediátricos. El objetivo de este estudio es presentar los resultados a corto plazo de la terapia de presión negativa en pacientes pediátricos con abdomen hostil debido a distintas etiologías. MATERIAL Y METODOS: Identificación y análisis retrospectivo de los pacientes pediátricos con abdomen hostil (< 18 años) tratados con terapia de presión negativa ABTHERA. RESULTADOS: Se incluyó a 7 pacientes. La mediana de edad fue de 16 años (rango: 9-17). 5 (71,4%) eran niños y 2 (28,6%) niñas. 3 (43%) presentaban antecedentes médico-quirúrgicos de interés (lupus eritematoso sistémico, apendicectomía complicada y derivación ventriculoperitoneal). El dispositivo se empleó a presión constante, entre ­50 y ­125 mmHg. Los hallazgos preoperatorios y postoperatorios se notificaron mediante la clasificación de Bjork. Los dispositivos se sustituyeron cada 4-7 días (mediana de 5 días). La cantidad total de reemplazos fue de 1-4 (mediana de 3). 5 (71,4%) pacientes precisaron ventilación mecánica invasiva durante la terapia de presión negativa debido al estado clínico. 4 (57%) pacientes recibieron nutrición enteral. 1 (14%) paciente requirió reintervención posterior al cierre definitivo por el desarrollo de un absceso retroperitoneal. El resultado, evaluado en base a la tolerancia oral, el movimiento intestinal y la ausencia de dolor, fue favorable en todos los pacientes. CONCLUSION: Los dispositivos de terapia de presión negativa aportan resultados favorables en los pacientes pediátricos con abdomen hostil, aunque se necesita más información para evaluar los ajustes de presión y la frecuencia de reemplazo del dispositivo.

Two-Step Fowler-Stephens orchiopexy for intra-abdominal testes: a 28-year single institution experience.

PURPOSE: Two-Step Fowler-Stephens orchiopexy for high undescended testes allows for mobilization of the testicle to the scrotal position while preserving perfusion by collateral circulation after gonadal vessel ligation. Although used for decades, the long-term efficacy of this procedure has not been reported. We present our 28-year clinical experience with this technique. MATERIALS AND METHODS: We retrospectively studied a cohort of patients who underwent 2-step Fowler-Stephens orchiopexy at our institution between 1982 and 2009. Patients were excluded if either step was performed elsewhere or if followup was less than 6 months. Bivariate and multivariate analyses were performed to determine associations between clinical, surgical and anatomical factors and testicular viability at last followup. RESULTS: A total of 62 patients (79 testes) met inclusion criteria. Median followup was 3.1 years (range 0.6 to 20). Based on the most recent examination/ultrasound, 70.9% of testicles were considered to be normal, with the remainder exhibiting relative (15.2%) or complete (14.9%) atrophy. Of the 10 testes assessed at or after puberty 6 were normal and 4 showed relative atrophy. On bivariate and multivariate analyses only an open second stage approach was associated with normal testicular viability, with 69.9% of normal vs 18.9% of completely atrophic testes being managed by an open approach (p = 0.0084). CONCLUSIONS: Thought to be highly effective in short-term followup, our data suggest that 2-step Fowler-Stephens orchiopexy leads to complete testicular viability in 70.9% of cases. This viability is strongly associated with an open second step.

Terlipressin therapy for moderate-to-severe hyponatraemia in patients with liver failure.

BACKGROUND: Hyponatraemia in liver failure is associated with increased morbidity and mortality. Improving serum sodium in liver failure has been observed in patients receiving terlipressin. METHODS: We assessed the response of hyponatraemia in patients with liver failure to terlipressin using comparative retrospective analysis. RESULTS: Twenty-three patients received terlipressin for hyponatraemia after failed conservative management (median age 52 years (27-67), model for end-stage liver disease score 28 (16-38)). The median therapy was 7 days (1-27), with an average total dose of 25 mg (4-90) and a mean follow up of 51 days (5-1248). These patients were compared with 11 hyponatraemic patients managed conservatively during the same period with comparable age, baseline serum sodium and follow up. After 1 week of terlipressin therapy, serum sodium increased from a median of 120 (115-128) to 129 mmol/L (121-144) (P < 0.001), and at the end of terlipressin therapy, the serum sodium had increased significantly to 131 mmol/L (120-148) (P < 0.001). In comparison, in the conservatively managed group, the serum sodium did not increase significantly from the baseline of 123 (117-127) mmol/L. Adverse events occurred in 26% of patients receiving terlipressin, which predominantly pulmonary oedema. Importantly, more hyponatraemic patients treated with terlipressin (48%) were alive compared with the conservative group (18%), despite the latter having a significantly lower baseline median MELD score of 21 (16-30) (P = 0.008). Moreover, the transplant-free survival was higher in the terlipressin (30%) compared with the conservative group (0%). CONCLUSIONS: Terlipressin is effective in treating hyponatraemia in liver failure. Importantly, terlipressin use results in better transplant-free survival but also more adverse events.

Patient and provider views on the use of medical services by women with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (ID) receive primary care in community-based practices and are encouraged to participate in the physician-patient relationship. However, the nature of this participation is not known. METHODS: Qualitative data were analysed to obtain perspectives from patients and providers regarding clinic visits. Patient participants were recruited from community organisations, while physician participants were recruited from emails and phone calls to local and regional practices and a national and regional list serve. Analysis methods derived from grounded theory were used. RESULTS: Twenty-seven women with ID and 22 family physicians were interviewed. Themes important to both groups included time, how the support worker should be used in the encounter and the nature of the physician-patient relationship. Patients expressed frustration at how little time they spent with their physician, and wished that physicians would speak directly to them instead of to their support worker. Physicians felt that patients with ID took too much time, and said that they preferred communicating with the support worker. The interviews also revealed unconscious biases about people with ID. CONCLUSIONS: Patient participation is encouraged for people with ID, but is limited because of both physician and patient factors. Greater awareness of these factors may improve care for patients with ID.

Prognostic value of temporal patterns of left atrial reservoir strain in patients with heart failure with reduced ejection fraction.

BACKGROUND: We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. METHODS: In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. RESULTS: Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10-0.41) and (0.13 (0.10-0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. CONCLUSION: LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr.

Insecticidal toxins from the bacterium Photorhabdus luminescens.

Transgenic plants expressing Bacillus thuringiensis (Bt) toxins are currently being deployed for insect control. In response to concerns about Bt resistance, we investigated a toxin secreted by a different bacterium Photorhabdus luminescens, which lives in the gut of entomophagous nematodes. In insects infected by the nematode, the bacteria are released into the insect hemocoel; the insect dies and the nematodes and bacteria replicate in the cadaver. The toxin consists of a series of four native complexes encoded by toxin complex loci tca, tcb, tcc, and tcd. Both tca and tcd encode complexes with high oral toxicity to Manduca sexta and therefore they represent potential alternatives to Bt for transgenic deployment.

Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.