A novel quantitative real-time PCR diagnostic assay for fecal and nasal swab detection of an otariid lungworm, Parafilaroides decorus.

Parafilaroides decorus, also known as sea lion lungworm, is a metastrongyloid nematode that infects otariid hosts, such as the charismatic California sea lion, Zalophus californianus. P. decorus causes bronchointerstitial pneumonia, respiratory distress, reduced ability to swim, dive and hunt and as a result, increased mortality particularly in young animals. Respiratory disease is a leading cause of stranding and admission to rehabilitation centers on the Pacific coast. Low-coverage genomic sequencing of four P. decorus individuals analyzed through Galaxy's RepeatExplorer identified a novel repeat DNA family we employed to design a sensitive quantitative PCR (qPCR) assay for diagnosing infections from fecal or sputum samples. The assay detects as little as 10 fg of P. decorus DNA and a linear regression model developed using a standard curve can be used to estimate the concentration of P. decorus DNA in a sample, ± 0.015 ng. This knowledge can be leveraged to estimate the level of parasite burden, which can be used to design improved treatments for animals in rehabilitation. Improved treatment of infections will aid in more animals being successfully released back into the wild.

Exaggeration of PFS by blinded, independent, central review (BICR).

BACKGROUND: Recent published studies have shown meaningful discrepancies between local investigator and blinded, independent, central review (BICR) assessed median progression-free survival (PFS). When the local review but not BICR shows progression, generally, no further assessments are carried out and patients are censored in the BICR analysis, leading to violation of the statistical assumptions of independence between censoring and outcome used in survival analysis methods. METHODS: We carried out a simulation study to assess methodological reasons behind these discrepancies and corroborated our findings in a case study of three BRCA-mutated ovarian cancer trials. We briefly outline possible methodological solutions that may lead to improved estimation of the BICR medians. RESULTS: The Kaplan-Meier (KM) curve for the BICR PFS can often be exaggerated. The degree of bias is largest when there is reasonably strong correlation between BICR and local PFS, especially when PFS is long compared with assessment frequency. This can result in an exaggeration of the medians and their difference; however, the hazard ratio (HR) is much less susceptible to bias. Our simulation shows that when the true BICR median PFS was 19 months, and patients assessed every 12 weeks, the estimated KM curves were materially biased whenever the correlation between BICR and local PFS was 0.4 or greater. This was corroborated by case studies where, in the active arm, the BICR median PFS was between 6 and 11 months greater than the local median PFS. Further research is required to find improved methods for estimating BICR survival curves. CONCLUSIONS: In general, when there is a difference between local and BICR medians, the true BICR KM curve is likely to be exaggerated and its true median will probably lie somewhere between the observed local and BICR medians. Presentation of data should always include both BICR and local results whenever a BICR is carried out.

Repeatability of measuring knee flexion angles with wearable inertial sensors.

BACKGROUND: As assessment with inertial-measurement-units (IMUs) increases in research and in clinics, it is important to be aware of the repeatability of these sensors. The objectives of this experiment were to evaluate the measurement repeatability of IMU joint angles using a repeatable robot controller and an anthropomorphic leg phantom and to determine effects of joint speed and sensor positioning on the angles collected by these sensors. Comparisons to an electro-goniometer and three-dimensional (3D) motion capture cameras were also completed. METHODS: Two dual-IMU setups (posterior and lateral) were tested concurrently with an electro-goniometer and 3D motion capture cameras using a repeatable robot controller and a leg phantom. All modalities were attached to the phantom, which was flexed 10 times using a pre-programmed motion pathway during each test. Mean angles were compared across tests. Effects of joint speed, sensor re-positioning, and anatomical placement of the sensors on repeatability were assessed. RESULTS: Re-positioning caused greater deviation to the maximum and minimum angles than differences in speed. Overall, the means ±â€¯standard deviations, and 95% confidence intervals of the maximum angles across all tests for the 3D camera markers, electro-goniometer, posterior IMUs, and lateral IMUs were 119.4 ±â€¯0.3° (119.4, 119.5), 112.4 ±â€¯0.5° (112.3, 112.5), 116.2 ±â€¯2.4° (115.7, 116.7), and 118.3 ±â€¯1.1° (118.1, 118.6). CONCLUSIONS: Both posterior and lateral IMU setups demonstrated acceptable repeatability in measurement of range of motion that was advantageous to manual goniometer methods. Posterior and lateral IMU setups demonstrated overlapping standard deviations about their means.

Randomised clinical trial: certolizumab pegol for fistulas in Crohn's disease - subgroup results from a placebo-controlled study.

BACKGROUND: Treatment options for fistulizing Crohn's disease (CD) are limited. AIM: To examine whether fistula closure is maintained at week 26 following treatment with certolizumab pegol. METHODS: Patients with draining fistulas at baseline from PRECiSE 2 (n = 108) received open-label induction with certolizumab pegol 400 mg at weeks 0 (baseline), 2 and 4. Response was defined as ≥100-point decrease from baseline in the Crohn's Disease Activity Index. Nonresponders (50/108) were excluded. At week 6, responders with draining fistulas (N = 58) were randomised to certolizumab pegol 400 mg (n = 28) or placebo (n = 30) every 4 weeks across weeks 8-24. Fistula closure was evaluated throughout the study, with a final assessment at week 26. RESULTS: The majority of patients (55/58) had perianal fistula. At week 26, 36% of patients in the certolizumab pegol group had 100% fistula closure compared with 17% of patients receiving placebo (P = 0.038). Protocol-defined fistula closure (≥50% closure at two consecutive post-baseline visits ≥3 weeks apart) was not statistically significant (P = 0.069) with 54% and 43% of patients treated with certolizumab pegol and placebo achieving this end point, respectively. CONCLUSION: Continuous treatment with certolizumab pegol improves the likelihood of sustained perianal fistula closure compared with placebo.

Clinical trial: impact of prior infliximab therapy on the clinical response to certolizumab pegol maintenance therapy for Crohn's disease.

BACKGROUND: Certolizumab pegol (CZP) is an effective therapy for Crohn's disease refractory to aminosalicylates, corticosteroids and immunosuppressants. In PRECiSE 2, patients were also eligible for enrolment if prior infliximab therapy was terminated due to loss of response. AIM: To evaluate prior infliximab therapy on sustained response and remission to CZP for Crohn's disease. METHODS: PRECiSE 2 were was analysed for predictors of sustained response and remission. Covariates included prior infliximab therapy, and baseline Crohn's Disease Activity Index (CDAI). RESULTS: Week 26 response (> or =100-point decrease from baseline CDAI) and remission (CDAI < or = 150) were greater with CZP vs. placebo in patients previously receiving infliximab (response: 44.2% vs. 25.5%, P = 0.018; remission: 32.7% vs. 13.7, P = 0.008) and infliximab-naïve patients (response: 68.7% vs. 39.6%, P < 0.001; remission: 52.8% vs. 33.3%, P < 0.001). Prior infliximab use was the only independent predictor of week 26 response and remission in both groups [response OR(CZP vs. placebo) = 3.06 (95% CI: 1.21-7.77); remission OR(CZP vs. placebo) = 4.22 (95% CI: 1.45-12.28)]. Adverse events were similar for both groups. CONCLUSIONS: Certolizumab pegol is an effective maintenance therapy in Crohn's disease regardless of prior infliximab use. Efficacy is higher in patients receiving CZP therapy as a first-line biologic, but approximately 50% of infliximab-experienced patients benefited from second-line CZP therapy.

An observational study of changes to long-term medication after admission to an intensive care unit.

Many patients admitted to intensive care units consume long-term medication. New drugs may be commenced during intensive care intended for the short term or longer. Patients are often cared for by several teams during hospital admission and long-term medication may inadvertently be permanently discontinued. Following admission, new therapies relevant only in the short term could be continued beyond intensive care and hospital discharge. We conducted a retrospective analysis of drug prescription by examining patients' notes and charts before, during and after intensive care admission. Of 197 drugs prescribed up to intensive care admission to 59 patients, 112 (57%) were stopped. Ninety-nine of these were not reintroduced by intensive care discharge and 34 were not reintroduced by hospital discharge. Of 154 drugs commenced during intensive care, 96 (62%) had no listed reason for their introduction. Twenty-eight were continued beyond hospital discharge, some without apparent ongoing indication. Reliable mechanisms to prevent prescription errors are required.

Chlorpheniramine is no more effective than placebo in relieving the symptoms of childhood atopic dermatitis with a nocturnal itching and scratching component.

BACKGROUND: Childhood atopic dermatitis (AD) is a common disorder affecting 15% of children aged over 18 months. AD is associated with intense nocturnal itching. The central sedative effect of antihistamines is thought to be useful in interrupting the itching cycle and may prevent exacerbations. OBJECTIVE: A multi-centred, double-blind, placebo-controlled study was carried out in 155 children to evaluate chlorpheniramine in alleviating symptoms of AD. METHODS: Assessments were carried out over a 4-week study period consisting of 3 visits to out-patient clinics. During the visits the severity of AD and itching was rated using a series of visual analogue scale (VAS) and 5-point rating scales. RESULTS: The use of chlorpheniramine resulted in no greater alleviation of AD symptoms than placebo. CONCLUSIONS: The findings contradict conventional wisdom that the sedative effect of earlier-generation antihistamines alleviates symptoms of AD. The study also indicates that the use of antihistamines in AD does not affect the amounts of topical treatment used over the short term.

The pharmacokinetics of a single intramuscular dose of amikacin in red-tailed hawks (Buteo jamaicensis).

The pharmacokinetic parameters of amikacin were determined in red-tailed hawks (Buteo jamaicensis) following the i.m. administration of a single 20 mg/kg dose. After a rapid absorption phase, mean amikacin serum concentrations peaked at 65 +/- 12 micrograms/ML 30-45 min following injection. The serum amikacin concentrations decreased to 2.3 +/- 2 micrograms/ml at 12 hr postinjection. Amikacin was eliminated with first-order kinetics characteristic of a single-compartment model with a half-life of 2.02 +/- 0.63 hr. The volume of distribution was estimated to be 0.28 +/- 0.03 L/kg. Forty-two isolates of gram-negative bacteria and coagulase-positive Staphylococcus species were cultured from birds of prey presented to the Veterinary Medical Teaching Hospital at the University of California-Davis. The minimum inhibitory concentration (MICs) of amikacin ranged from 0.5 to 8.0 micrograms/ml (mean = 2.5 micrograms/ml). The 20 mg/kg dose used in this study resulted in serum concentrations at or above the MICs for > 12 hr for most of the isolates examined. The heaviest birds had the lowest peak serum amikacin concentrations, and the lightest birds had the highest, despite exact volume replacement for each sample drawn. This observation suggests that doses should be based on factors other than weight alone. Amikacin administered at 15-20 mg/kg/day, either as a single dose or divided into two or three doses, is effective in treating sensitive pathogens of the red-tailed hawk.

Blood pressure monitor-induced petechiae and ecchymoses.

A case is presented of a diabetic, hypertensive, female patient who suffers from a bleeding complication from application of an ambulatory blood pressure monitor. A recent literature search is referred to and practitioners are cautioned against this adverse reaction.

Racial differences in perceptions concerning hypertension and its consequences.

To investigate racial differences in hypertensive patients' understanding of their disorder, we administered a questionnaire to 83 black and 260 white outpatients with the diagnosis of hypertension designated in their medical chart. No racial differences in systolic or diastolic blood pressure, age, or male/female ratio were observed. However, blacks were more likely than whites to identify renal failure as a consequence of hypertension, whereas whites were more likely to identify atherosclerosis. Blacks also were more likely than whites to accept higher diastolic blood pressures as normal (90 to 100 mm Hg versus 80 to 90 mm Hg). There was no correlation between knowledge and blood pressure. Our observations show that both racial groups are well educated about antihypertensive therapy as well as the consequences and complications of hypertension. Comprehensive treatment of hypertension should include educational strategies that are population-specific and that address ways to change disease-relevant behaviors, rather than merely identifying which behaviors to change.