Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis.

BACKGROUND: Infections are associated with biological therapies in psoriasis. OBJECTIVES: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody. METHODS: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. RESULTS: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. CONCLUSIONS: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.

Racial/ethnic differences in accuracy of body mass index reporting in a diverse cohort of young adults.

Surveillance data describing the weight status of the U.S. population often rely on self-reported height and weight, despite likely differences in reporting accuracy by demographics. Our objective was to determine if there were racial/ethnic differences in accuracy of self-reported body mass index (BMI) in a diverse nationally representative sample of young people. Using data from Wave III (data collected in 2001-2002) of the National Longitudinal Study of Adolescent Health when respondents were aged 18-26, we used gender-stratified multivariable linear regression models to examine the association of race/ethnicity and self-reported BMI controlling for measured BMI while also adjusting for factors known to be associated with weight self-perception. Black males and females (b(Female)=0.45, confidence interval (CI): 0.19, 0.71; b(Male)=0.34, CI: 0.17, 0.51) and Hispanic females (b(Female)=0.30, CI: 0.08, 0.52) and Native American males (b(Native) American=0.87, CI: 0.15, 1.58) reported higher BMIs than their similarly weighted White peers, leading to more accurate BMI reporting in these groups at higher BMIs. Caution should be taken in interpreting results from studies relying on self-reported BMI, as they may exaggerate racial/ethnic differences in weight status.

General practice in the Armed Forces: a definition and model.

Armed Forces General Practice is in an unprecedented time of challenge with the demands of contiguous worldwide operations in austere environments, reorganisation of defence, budgetary constraints and manpower shortfalls. We propose a model of this crucial area of military medical care as a key academic and practical reference point, which will help retain, and perhaps even enable, the development of this clinical speciality over the next decade. It provides a formalised definition and a basis for education, training and research in Military General Practice; it also has the advantage of highlighting the all-encompassing nature of military primary care when compared to the nearest equivalent model--that of civilian General Practice.

High risk occupations for non-Hodgkin's lymphoma in New Zealand: case-control study.

OBJECTIVES: Previous studies into occupational risk factors for non-Hodgkin's lymphoma (NHL) in New Zealand have indicated that farmers and meat workers are at increased risk for these neoplasms. A new nationwide case-control study was conducted to assess whether previously observed associations persist and to identify other occupations that may contribute to the risk of NHL in the New Zealand population. METHODS: A total of 291 incident cases of NHL (age 25-70 years) notified to the New Zealand Cancer Registry during 2003 and 2004, and 471 population controls, were interviewed face-to-face. The questionnaire collected demographic information and a full occupational history. The relative risk for NHL associated with ever being employed in particular occupations and industries was calculated by unconditional logistic regression adjusting for age, sex, smoking, ethnicity and socioeconomic status. Estimates were subsequently semi-Bayes adjusted to account for the large number of occupations and industries being considered. RESULTS: An elevated NHL risk was observed for field crop and vegetable growers (OR 2.74, 95% CI 1.04 to 7.25) and horticulture and fruit growing (OR 2.28, 95% CI 1.37 to 3.79), particularly for women (OR 3.44, 95% CI 0.62 to 18.9; OR 3.15, 95% CI 1.50 to 6.61). Sheep and dairy farming was not associated with an increased risk of NHL. Meat processors had an elevated risk (OR 1.97, 95% CI 0.97 to 3.97), as did heavy truck drivers (OR 1.98, 95% CI 0.92 to 4.24), workers employed in metal product manufacturing (OR 1.92, 95% CI 1.12 to 3.28) and cleaners (OR 2.11, 95% CI 1.21 to 3.65). After semi-Bayes adjustment the elevated risks for horticulture and fruit growing, metal product manufacturing and cleaners remained statistically significant, representing the most robust findings of this study. CONCLUSIONS: This study has confirmed that crop farmers and meat workers remain high risk occupations for NHL in New Zealand, and has identified several other occupations and industries of high NHL risk that merit further study.

Contribution of vibration to musculoskeletal disorders in New Zealand.

The aim of this study was to remind Australasian doctors about the importance of vibration as an occupational exposure capable of causing musculoskeletal disease. This is a common problem in the northern hemisphere, but only four reports have been found in Australasian published work. Nine cases are reported together with a summary of vibration disorders and their nomenclature. Of the nine cases reviewed, six arose from compensation disputes and two resulted in Department of Labour prosecutions. Three patients had hand symptoms arising from using vibrating concrete drills, two patients used heavy floor-polishing machines in hospitals and three used heavy metal polishing machines. One had general pain from whole-body vibration in a digging machine. Minor circulatory signs were found in two patients, but cold exposure was not noted. Vibration disease is underreported in New Zealand. Doctors must question patients about vibration exposure in taking an occupational history, as vibration is an important factor in the causation of occupational musculoskeletal disorders. As vibration can be controlled, illness can be prevented.

Occupational bladder cancer in New Zealand: a 1-year review of cases notified to the New Zealand Cancer Registry.

AIM: To identify which cases of adult bladder cancer notified to the New Zealand Cancer Registry in 2001 had a probable occupational cause. METHODS: Occupational Safety and Health (OSH), in conjunction with the Massey University Centre for Public Health Research, interviewed and obtained an occupational history for 210 (162 men, 48 women) cases. RESULTS: Of the 162 male cases (response rate 65%), 45 (28%) were considered to be 'probable' occupational cancers. Of the 48 female cases (response rate 76%), three cases (6%) were considered to be 'probable' occupational cancers. The largest occupational group for men was truck drivers, which made up 51% of probable cases. Other common groups were engineering and metal workers (18%), crop farmers/orchardists (7%), textile and leather workers (7%), painters/furniture finishers (7%), and plastics manufacturing workers (4%). The three female cases considered to be of occupational origin included two textile workers and one telephonist. CONCLUSIONS: The percentage of cases considered to be of occupational origin is similar to that reported in Europe and the United States, indicating that occupational cancer is a major occupational health problem in New Zealand as it is in other parts of the world.

Failure after 5 years of self-regulation: a health and safety audit of New Zealand engineering companies carrying out welding.

The aim of this study was to audit the degree of compliance with new health and safety legislation 5 years after enactment in a typical cross-section of New Zealand manufacturing industries. To this end, 299 randomly selected enterprises using a welding process were visited by Occupational Safety and Health Officers of the Department of Labour. An interviewer-administered questionnaire concerning the nature of the hazards encountered in that enterprise and the chosen control measures employed to protect the health of their employees was undertaken and analysed. Only 40% of New Zealand businesses in this sample undertaking welding had adopted the most basic of regulatory requirements to control health and safety risks. This percentage seemed independent of employer size. Fundamental safety issues (e.g. welding in confined spaces) were ignored by >50% of enterprises. In conclusion, self-management of health and safety risks had not occurred in over half the enterprises surveyed.

Do electric patient beds reduce the risk of lower back disorders in nurses?

The aim of this study was to compare the probability estimates of lower back disorder (LBD) for a nurse performing a range of simulated patient care activities involving manual and electric patient beds. Studies of simulated patient care involving patient beds were undertaken using electrically powered and manually operated patient beds. The estimated probabilities of back injury, as calculated by the Lumbar Motion Monitor (LMM), between the two beds were compared statistically. A statistically significant reduction in LBD probability was observed in those functions that were completely achieved by the electrical mechanism. No significant difference in risk was observed in the patient care activities involving manipulating the patient in and around the bed that are more typical of 'heavy' orthopaedic nursing care in a busy acute ward environment. A potential for increased patient independence was observed during this trial. The LMM recorded no real risk reduction between situations involving electric or manual patient beds in those actions typically required of nurses in an acute orthopaedic ward caring for a disabled patient.

The distribution of occupations in two populations with upper limb pain.

Occupations of two geographically distinct populations of patients with upper limb pain were examined. Relative risks for being in an occupation were calculated for subjects with epicondylitis, carpal tunnel syndrome, and pain syndromes in one population and nonspecific occupational overuse syndrome (OOS) in the other. Population A subjects (806 female, 154 male Auckland clinic referrals) with epicondylitis and carpal tunnel syndrome had higher rates of manual occupations compared with the Auckland employed population, consistent with previous research. Both Population A and Population B subjects (1,188 female, 499 male national notifications to the Department of Labour) with pain syndrome or nonspecific OOS had increased rates of clerical occupations. Relative risks ranged from 2.24 (95% CI 1.69,2.97) to 3.92 (3.50 ,4.40). Word processor operators, data-entry operators, and mail sorters were overrepresented in both populations. An unexplained association between nonspecific upper arm pain and being in some clerical occupations requires further research.

An environmentally benign soybean derived fuel as a blending stock or replacement for home heating oil.

The use of bio-derived materials both as fuels and/or as blending stocks becomes more attractive as the price of middle distillate fuels, especially home heating oil, continues to rise. Historically, many biomass and agricultural derived materials have been suggested. One of the most difficult problems encountered with home heating oil is that of storage stability. High maintenance costs associated with home heating oil are, in large part, because of this stability problem. In the present research, Soygold, a soybean derived fuel, was added in concentrations of 10%-20% to both a stable middle distillate fuel and an unstable home heating oil. Fuel instability in this article will be further related to the organo-nitrogen compounds present. The soy-fuel mixtures proved stable, and the addition of the soy liquid enhanced both the combustion properties, and dramatically improved the stability of the unstable home heating oil.

Hazards associated with the boat building industry in New Zealand: an OSH audit.

AIM: To randomly audit the boat building industry in New Zealand to assess the occupational health status and level of knowledge of employees. METHODS: A survey was conducted using a nurse and inspector administered questionnaire. 151 workers from 120 randomly selected firms participated in the survey. RESULTS: 31.5% respondents thought they had had some sort of work related health problem since working in that job. 22% reported wheezing during the last twelve months. 14-16% met criteria for occupational causation, and 4% met a measure of severe wheezing related to work. 25.6% of workers had dermatitis. Only a quarter of these met criteria for occupational causation. No respondents reported symptoms suggestive of chronic solvent neurotoxicity. Solvents and epoxy resins comprised the majority of chemicals with which there was contact. Observation suggested little use of Material Safety Data Sheets as a source of knowledge about toxicity of the chemicals used. Although 94.3% reported wearing gloves, this did not correlate with numbers reporting dermatitis suggesting non-compliance or glove failure. CONCLUSION: New Zealand boat builders and their employees remain at risk for occupational health problems by virtue of their employment.

Bioavailability of the oral selective phosphodiesterase 4 inhibitor cilomilast.

STUDY OBJECTIVE: To determine the absolute bioavailability of cilomilast, and assess the effects of food, dosing time, and coadministration of antacid agents on its bioavailability and pharmacokinetics in healthy volunteers. SETTING: Clinical pharmacology unit. DESIGN: Five prospective pharmacokinetic studies: one single-blind, dose-escalating, placebo-controlled trial; four open-label, randomized studies. SUBJECTS: Ninety-six healthy adult volunteers who were nonsmokers. INTERVENTION: In the first study, four subjects received intravenous cilomilast 1, 2, and 4 mg. In the second study, 16 subjects received oral cilomilast 15 mg or intravenous cilomilast 4 mg. In the other three studies, a total of 76 subjects were given single oral 15-mg doses; one study compared its effects in fed versus fasted subjects, one looked for differences of morning versus evening dosing, and one examined coadministration with aluminum hydroxide-magnesium hydroxide. MEASUREMENTS AND MAIN RESULTS: After intravenous administration of cilomilast, plasma concentrations increased in an approximately dose-proportional manner; the half-life, approximately 6.5 hours, was dose independent. Cilomilast clearance and volume of distribution were small. After oral dosing, the absolute bioavailability was consistently close to 100%. Absorption was slower in fed subjects than in fasted (median 2-hr delay in time to reach maximum plasma concentration, average 39% reduction in maximum plasma concentration), but the area under the concentration-time curve from time zero to infinity (systemic availability) was unaffected. Pharmacokinetic parameters were not influenced by time of dosing or coadministration of antacid. CONCLUSION: The absolute bioavailability of oral cilomilast was 100%; it was not adversely affected by time of dosing or coadministration with food or antacid.

In vitro activities of terbinafine against Aspergillus species in comparison with those of itraconazole and amphotericin B.

Compared with the in vitro activities of itraconazole (geometric mean MIC [GM], 0.56 microg/ml) and amphotericin B (GM, 0.66 microg/ml), the in vitro activity of terbinafine was inferior against Aspergillus fumigatus (GM, 19.03 microg/ml) (P < 0.05) and superior against A. flavus (GM, 0.10 microg/ml), A. terreus (GM, 0.16 microg/ml), and A. niger (GM, 0.19 microg/ml). Clinical correlation is required, as trailing endpoints are problematic.

Pathologic changes in grossly normal menisci in dogs with rupture of the cranial cruciate ligament.

OBJECTIVE: To determine whether histopathologic changes are detectable in grossly normal medial menisci from dogs with rupture of the cranial cruciate ligament (CCL). DESIGN: Case series. SAMPLE POPULATION: 40 medial menisci from dogs with rupture of the CCL and 20 medial menisci from control dogs without stifle joint disease. PROCEDURE: Data evaluated included age, duration of clinical signs, and whether rupture of the CCL was complete or incomplete. Three groups (n = 20/group) were also compared on the basis of 5 histologic criteria; group-1 menisci appeared grossly normal and were obtained from dogs with naturally occurring rupture of the CCL, group-2 menisci were grossly abnormal and were also obtained from dogs with naturally occurring CCL ruptures, and group-3 menisci were collected at postmortem from dogs without stifle joint disease that were of similar age and weight as dogs in groups 1 and 2. RESULTS: Group-2 menisci were significantly different from group-1 and -3 menisci in all histologic criteria. Group-1 menisci were significantly different from control menisci in only 1 of the 5 histologic criteria (cartilage differentiation). Dogs that were > or =3 years old had significantly more surface cellularity than did dogs that were < 3 years old. A significant difference was not detected between groups 1 and 2 with regard to completeness of rupture. CONCLUSIONS AND CLINICAL RELEVANCE: Histologic changes in meniscal cartilage correlate with gross appearance of the cartilage at time of surgery for rupture of the CCL. On the basis of minimal histologic changes, routine removal of grossly normal menisci does not appear to be warranted.

In vitro activity of the new triazole BMS-207147 against Aspergillus species in comparison with itraconazole and amphotericin B.

The in vitro activity of BMS-207147 against 80 clinical isolates of Aspergillus was compared with that of itraconazole and amphotericin B, using a validated microtiter method. Geometric mean MICs (in microg/ml) were as follows: 1.71 for BMS-207147, 0.67 for itraconazole, and 0.63 for amphotericin B. The range of concentrations of each drug was 0.125 to >16 microg/ml. Aspergillus fumigatus was significantly more susceptible to BMS-207147 (P < 0. 05) than A. terreus and A. flavus. No BMS-207147-resistant A. fumigatus isolates were identified, though eight itraconazole-resistant (MIC, >8 microg/ml) isolates were. BMS-207147 is active against Aspergillus spp. at slightly high concentrations compared with itraconazole and amphotericin B.