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.

An estimation of mineral losses through arm sweat of preadolescent children.

Balance studies were conducted to determine the effects of three levels of nitrogen intake on the loss of nitrogen through sweat in preadolescent boys and girls. During the studies, the losses of calcium, iron, magnesium, manganese, potassium, sodium, and zinc were determined in the arm sweat of the subjects. Sweat from the forearm was collected in a polyethylene bag for 1 hr on three different occasions. Using the concentrations of nitrogen in the arm bag and in the whole body collection and the concentration of minerals in the arm bag, the total body loss of minerals were estimated. Losses of minerals through sweat, expressed as a percentage of intake, ranged from 0.12 to 1.10%. Under conditions of these studies, sweat losses of the essential minerals were not a significant factor in estimating total losses.

Subcutaneous phaeohyphomycosis caused by Exserohilum rostratum in an immunocompetent host.

A healthy, 55-year-old woman developed a subcutaneous abscess and systemic symptoms of nausea, dizziness, and chills following minor trauma to her leg. Histopathologic examination of a skin biopsy specimen revealed golden-brown colored mycelial elements, and culture resulted in growth of a dematiaceous fungus identified as Exserohilum rostratum. Surgical excision of the abscess and concomitant oral therapy with ketoconazole resulted in resolution of symptoms. In previously reported cases of human phaeohyphomycosis caused by Exserohilum and related Bipolaris species in both immunocompromised and immunocompetent hosts, treatment has varied from topical antimicrobial therapy to combined surgery and intravenous antifungal chemotherapy. Our experience leads us to believe that surgical débridement of an accessible focus of infection along with orally administered ketoconazole may provide adequate therapy in an immunocompetent host.

Psychosocial factors associated with the stages of change for condom use among women at risk for HIV and STDs: implications for intervention development.

This study examined the prevalence of consistent condom use among inner-city women at risk for HIV, measured the distribution of these women across the stages of change for condom use, determined psychosocial factors associated with the stages, and suggested intervention strategies based on the results. The 5-city sample of women aged 15-34 years consisted predominantly of African Americans. Only 18% reported consistent condom use with main partners and 45% with other partners. Logistic regressions compared women in each stage of change with those in higher stages for each partner type. Results indicated that women who practice or intend to practice consistent condom use were more likely to talk with others about condoms, acknowledge the advantages of condoms, have higher self-efficacy for condom use, and indicate that people important to them favored condom use. Intervention approaches are suggested for women in different stages of change for condom use.

PIP: This cross-sectional study examines the prevalence of consistent condom use among inner-city women at risk for HIV and measured the distribution of these women across the stages of change for condom use. It further determined the psychosocial factors that could be used by program planners to design interventions for these women in different stages of change. The study sample was composed of women aged 15-34 years who were mostly African-Americans (79%). In the results, only 18% reported consistent condom use with main partners and 45% with other partners. The results further indicated that women who practice or intend to practice consistent condom use were more likely to talk with others about condoms, acknowledge the advantages of condoms, have higher self-efficacy for condom use, and state that people important to them favored condom use.

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.

Informal support from black churches and the well-being of elderly blacks.

This paper explores the type of support black churches and families provide, and how that support relates to the well-being of elderly blacks. Findings indicate that the family network is perceived as more supportive than the church network, but that church support contributes to feelings of well-being. Perceptions of support from the churches and not the spiritual aspects of religion or involvement in organized religious activities were associated with well-being.

The role of apheresis in the support of life-threatening ITP relapse.

A 14-year-old girl with chronic idiopathic thrombocytopenic purpura (ITP) presented in relapse with a platelet count of 1,000/microL and a high-level serum antiplatelet IgG antibody. She previously had been unresponsive to courses of therapy with steroids, vincristine, and splenectomy. When treatment with danazol and purified immunoglobulins was unsuccessful in controlling her rapidly progressive course, an 8-day plasma exchange procedure was initiated in combination with platelet transfusion therapy and immunosuppression with cyclophosphamide and vincristine. Within 2 days, her clinical state improved markedly, correlating with a drop in her serum antiplatelet antibody level. She continued to improve and was discharged on a regimen of cyclophosphamide and danazol. Her antiplatelet antibody level had fallen to within the normal range, despite a typical platelet count of 5,000/microL during the 8-day period. Two weeks later her platelet count rose to 65,000/microL. This case suggests that a course of therapeutic plasma exchange may have a temporizing role in the acute management of life-threatening chronic ITP relapse, generating time for the more definitive therapy of immunosuppression to take effect.

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.

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.

Accident consultations in one month in a semirural town.

General practice statistics for the month of July 1986 were analysed from a semirural town. There were 498 accident consultations and Maoris tended to be underrepresented. Thirty six percent of accidents were at work, 30% in the home and 12.6% in sports. Twenty three percent of the accidents involved no time off work and 32% had up to a week off. Thirty percent made a claim for earnings related compensation to ACC. Eight patients had prolonged periods off work.

Implementing tuberculosis control guidelines in a hospital environment.

AIM: This review assessed the effectiveness and results of a programme implementing the 1992 Tuberculosis Control Guidelines to hospital staff at Green Lane and National Women's hospitals. METHODS: All staff tuberculosis surveillance and patient contact tracing contacts carried out by the occupational health unit and the resultant outcomes were assessed. RESULTS: A higher risk of Mantoux conversion does exist in hospital staff. These conversions occur in nonhigh risk occupational groups as well as the more recognized at risk groups. CONCLUSIONS: The 1992 guidelines proved impracticable to administer effectively and were resource intensive. Hospital staff form a distinct, well educated occupational group who are able to make their own risk assessments about the lifetime risks of tuberculosis infection. The British Thoracic Society Guidelines for screening healthcare workers make a practical surveillance programme. Tuberculosis remains a risk for healthcare workers and the emphasis of any staff programme should broaden from surveillance aimed at identifying primary infection having occurred to include improved environmental measures, work practices and the use of personal protection to reduce the work related exposure to the mycobacterium.

Health and safety standards in New Zealand mortuaries.

AIM: To establish the degree of compliance with health and safety standards in New Zealand mortuaries. METHOD: A mortuary audit tool was developed based mainly on British mortuary health and safety standards. This was tested and then applied to all identified mortuaries. RESULTS: Less than 50% (seven out of 15 institutions) met the standards required to carry out "basic" autopsies. Only one institution had mortuary facilities that were deemed suitable for "high risk" procedures. Where necessary, recommendations for improvements were made. CONCLUSIONS: New Zealand (and preferably Australasian-wide) standards need to be established and adopted for mortuaries. Some rationalisation of mortuary services so as to isolate risk (and improve quality control?) is necessary. People working in mortuaries need to adhere to stricter work practices while working in purpose-designed environments that minimise their risk.

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.

Occupational asthma cases notified to OSH from 1996 to 1999.

AIMS: To update notifications to the Occupational Safety and Health Service of the Department of Labour (OSH) Notifiable Occupational Disease System (NODS) from June 1996 to the beginning of 1999. METHODS: All notifications received for non-asbestos related occupational respiratory disease were reviewed to confirm the clinical diagnosis, occupational causation, and to identify the causative agent where possible. RESULTS: 54 cases of asthma were notified, of which 21 (39%) were accepted as being occupationally caused. These cases arose from 'predictable' industries. CONCLUSIONS: NODS offers sentinel data from interested practitioners and workplaces. Occupational asthma and other occupational respiratory diseases remain poorly notified to this system. NODS confirms the presence of occupational asthma in New Zealand from predictable and preventable causes not dissimilar to other countries. This data collection system needs supplementation by other mechanisms.

Occupational asthma and other nonasbestos occupational respiratory diseases notified between 1993 and 1996.

AIM: To review notifications to the Occupational Safety and Health Service of the Department of Labour Notifiable Occupational Disease System since its inception until June 1996. METHODS: All notifications received for non asbestos related occupational respiratory disease were reviewed to evaluate the outcome of the notification and to identify the causative agent where possible. RESULTS: There were 277 cases notified and investigated including worksite investigations. Of these 73 cases were confirmed as having occupational asthma, 35 by the asthma validation panel. Nineteen cases of other occupational respiratory disease were notified of which 11 were reviewed by the panel. Extrinsic allergic alveolitis secondary to organic dusts was the most common such notification. CONCLUSIONS: Isocyanates are well recognised as a cause of occupational asthma in New Zealand. It is suspected that occupational asthma and other occupational respiratory diseases are poorly notified to this system. Better mechanisms are needed to identify occupational causes of respiratory (and other) disease.

Health effects of occupational pentachlorophenol exposure in timber sawmill employees: a preliminary study.

AIMS: To study the health effects of pentachlorophenol (PCP) exposure in the timber sawmill industry. METHOD: A questionnaire-based, non-random survey was undertaken amongst a group of current and ex-workers who had identified their health concerns as being related to PCP exposure. RESULTS: Low, medium and high exposure groups were identified. A significant dose-response was found between past exposure to Pentachlorophenol and reported symptoms of fever/sweating (47% in the high exposure group), weight loss (33% in the high exposure group), persisting fatigue (74% in the high exposure group), nausea (40% in the medium and high exposure groups) and responses to a screening test for neuropsychological dysfunction (Questionnaire 16) (81% in the high exposure group). No associations were observed with other chronic diseases, apart from emphysema and chronic bronchitis. CONCLUSIONS: This study is based on a self selected sample of PCP-exposed workers whose precise exposure levels are unclear. Thus the findings presented should be regarded as preliminary. Nevertheless, they support clinical experiences and point to the need for further investigation.