A cluster randomized trial of strategies to increase uptake amongst young women invited for their first cervical screen: The STRATEGIC trial.

Objectives To measure the feasibility and effectiveness of interventions to increase cervical screening uptake amongst young women. Methods A two-phase cluster randomized trial conducted in general practices in the NHS Cervical Screening Programme. In Phase 1, women in practices randomized to intervention due for their first invitation to cervical screening received a pre-invitation leaflet and, separately, access to online booking. In Phase 2, non-attenders at six months were randomized to one of: vaginal self-sample kits sent unrequested or offered; timed appointments; nurse navigator; or the choice between nurse navigator or self-sample kits. Primary outcome was uplift in intervention vs. control practices, at 3 and 12 months post invitation. Results Phase 1 randomized 20,879 women. Neither pre-invitation leaflet nor online booking increased screening uptake by three months (18.8% pre-invitation leaflet vs. 19.2% control and 17.8% online booking vs. 17.2% control). Uptake was higher amongst human papillomavirus vaccinees at three months (OR 2.07, 95% CI 1.69-2.53, p < 0.001). Phase 2 randomized 10,126 non-attenders, with 32-34 clusters for each intervention and 100 clusters as controls. Sending self-sample kits increased uptake at 12 months (OR 1.51, 95% CI 1.20-1.91, p = 0.001), as did timed appointments (OR 1.41, 95% CI 1.14-1.74, p = 0.001). The offer of a nurse navigator, a self-sample kits on request, and choice between timed appointments and nurse navigator were ineffective. Conclusions Amongst non-attenders, self-sample kits sent and timed appointments achieved an uplift in screening over the short term; longer term impact is less certain. Prior human papillomavirus vaccination was associated with increased screening uptake.

Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients.

RATIONALE: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking. OBJECTIVES: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features. METHODS: uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts. MEASUREMENTS AND MAIN RESULTS: In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease. CONCLUSIONS: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.

Safety, tolerability, pharmacokinetics, and antiviral activity of GSK2336805, an inhibitor of hepatitis C virus (HCV) NS5A, in healthy subjects and subjects chronically infected with HCV genotype 1.

GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of ≥10 mg resulted in a statistically significant ≥2-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (t1/2) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a median tmax (time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.).

Chronic widespread pain is associated with slower cognitive processing speed in middle-aged and older European men.

Evidence from clinic-based studies suggests that the fibromyalgia syndrome (FMS) is associated with impairment in cognitive function though the mechanism is unclear. The aim of this analysis was to determine whether there is a similar association between chronic widespread pain (CWP), a cardinal feature of FMS, and impaired cognition in a community setting. Men (n=3369, 40-79 years) were recruited from population registers in eight centres for participation in the European Male Ageing Study (EMAS). The subjects completed a pain questionnaire and pain manikin, with the presence of CWP defined using the American College of Rheumatology criteria. The cognitive functions measured were visuospatial-constructional ability and visual memory (Rey-Osterrieth Complex Figure [ROCF]); visual recognition (Camden Topographical Recognition Memory test [CTRM]); and psychomotor processing speed (Digit-Symbol Substitution test [DSST]). We restricted our analysis to those subjects reporting pain that satisfied the criteria for CWP and those who were pain free. Of these 1539 men [mean (SD) age 60 (11) years], 266 had CWP. All cognitive test scores declined cross-sectionally with age (P<0.05). In age-adjusted linear regressions men with CWP had a lower DSST score (ß=-2.4, P<0.001) compared to pain-free subjects. After adjustment for lifestyle and health factors the association between pain status and the DSST score was attenuated but remained significant (ß=-1.02, P=0.04). There was no association between CWP and the ROCF-copy, ROCF-recall or CTRM scores. CWP is associated with slower psychomotor processing speed among community-dwelling European men. Prospective studies are required to confirm this observation and explore possible mechanisms for the association.

Post-treatment skin reactions reported by cancer patients differ by race, not by treatment or expectations.

Cancer patients may experience skin problems while undergoing chemotherapy and radiation therapy. Frequency of skin reactions may be influenced by skin pigmentation and psychological factors. A Symptom Inventory completed by 656 cancer patients nationwide before and after chemotherapy, radiation therapy, or chemotherapy plus radiation therapy was analysed to determine if treatment type, race (Black vs White), and pretreatment expectations influenced post-treatment skin reactions. Subsequent analysis of a local Symptom Inventory completed weekly for 5 weeks by 308 patients receiving radiation therapy examined severity of reported skin reactions. Significantly more patients receiving radiation therapy had stronger expectations of skin problems (62%) than patients receiving chemotherapy (40%, P=0.001) or chemotherapy plus radiation therapy (45%, P=0.003). Overall, expectations did not correlate with patient reported post-treatment skin problems in white (r=0.014, P=0.781) or black (r=0.021, P=0.936) patients. Although no significant difference was found between black and white patients in their pretreatment expectations of skin problems (P=0.32), black patients (10 out of 18, 56%) reported more skin problems than white patients (90 out of 393, 23%, P=0.001). Similarly, the local study showed that significantly more black patients (1 out of 5, 20%) reported severe skin reactions at the treatment site than white patients (12 out of 161, 8%). A direct correlation was observed between severity of skin problems and pain at the treatment site (r=0.541, P<0.001). Total radiation exposure did not significantly correlate with the report of skin problems at the treatment site for white or black patients. Overall, black patients reported more severe post-treatment skin problems than white patients. Our results suggest that symptom management for post-treatment skin reactions in cancer patients receiving radiation treatment could differ depending on their racial background.

High-performance liquid chromatographic assay for abacavir and its two major metabolites in human urine and cerebrospinal fluid.

A simple, reversed-phase HPLC assay has been developed and validated to measure the HIV-1 reverse transcriptase inhibitor abacavir and its two major metabolites, a 5'-glucuronide and a 5'-carboxylate, in human urine and cerebrospinal fluid. Sample preparation involved centrifuging to minimize particulates, then diluting the supernatant before HPLC separation and ultraviolet detection at 295 nm. The method described was used successfully to measure concentrations of abacavir and its two major metabolites in urine and cerebrospinal fluid from HIV-1 infected subjects.

Pituitary gene mutations and the growth hormone pathway.

Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

Finding patients after 40 years: a very long term follow-up study of the Colonna arthroplasty.

Between 1952 and 1965, surgeons at the Los Angeles Shriners Hospital managed 23 hips with the Colonna two-stage capsular arthroplasty, a procedure originally described in 1936 with very stringent indications for the treatment of childhood hip dysplasia. By using chart review, credit traces, telephone listings software, and the Internet, we found 17 (90%) of 19 patients known to be alive 40 years after surgery. Only four of 16 patients questioned have not undergone total hip arthroplasty, and these patients were no better candidates for the Colonna arthroplasty than were the 12 patients who have required hip-replacement surgery. We do not support revival of this now obscure procedure. However, we do attest that the average clinical investigator currently has access to tools that allow reliable location of patients for very long term follow-up. This technology will improve the accuracy and statistical power of outcomes research.

Comparison of crossed pins and external fixation for correction of angular deformities about the knee in children.

External fixation was compared to crossed Steinman pins and plaster for fixation after osteotomy about the knee in children. A group of 26 patients treated by external fixation was compared to a control group of 26 patients fixed with crossed Steinman pins and casting. The groups were matched for age, height, and weight. Overall there was a 100% union rate. Preoperative deformity and postoperative correction were similar in the two groups. The time to union was significantly longer, and there were significantly more complications in the external fixator group. There were 16 complications (62%) in the external fixator group and five (19%) in the control group. Complications included pin tract infections, peroneal nerve palsy, and delayed union. External fixation provides certain advantages for fixation after osteotomies about the knee in children but is associated with a variety of complications.

The impact of restraints on nursing home resident outcomes.

This article is an examination of the impact of physical restraints on physical activities of daily living (PADL), walking, and orientation to reality outcomes among nursing home residents. Computerized assessment data for a cohort of 5073 Virginia Medicaid nursing home admissions with complete data for their first and second post-admission assessments were analyzed. Multiple regression analysis was used to compare the outcomes of restrained and nonrestrained residents, after controlling statistically for the influence of case mix variables that might impact outcomes. Restraint use was associated with increased PADL dependence and disorientation for residents restrained at first and second assessment, both assessments, and either assessment. Restraint was associated with increased walking dependence for residents restrained at their second assessment and either assessment.

The impact of federal regulations on urethral catheterization in Virginia nursing homes.

The 1990 Omnibus Budget and Reconciliation Act (OBRA) nursing home regulations limit the use of indwelling urinary catheterization to certain appropriate cases. This study examines the impact of OBRA on catheterization among 3149 pre-OBRA and 5073 post-OBRA Virginia residents. The two cohorts were similar in activities of daily living function and medical status, but the post-OBRA cohort was more incontinent. A higher percentage of residents were catheterized pre-OBRA than post-OBRA. Post-OBRA, catheterized residents were more likely to meet OBRA conditions for appropriate catheterization than noncatheterized residents, and less than 1% of long-term catheterized residents were catheterized inappropriately. Long-term catheterized residents had more urinary tract infections than short-term catheterized residents, however. Also, some nursing homes may substitute ostomies for catheters. Catheter use may no longer be a reliable indicator of quality of care at the nursing home level, if homes are minimizing catheterization in response to OBRA.

A community survey approach to gerontology curriculum development.

A Nevada Geriatric Education Center (NGEC) study examined the relationship between gerontology content in the curriculum at two southern Nevada academic institutions and the usefulness of that content to community allied health providers. Course content for 20 gerontology topics was compared with community respondents' perceptions of topic usefulness. Rank-ordered topic content and usefulness means were associated positively for the total sample, nonwhites, social workers, managers and supervisors and nurses for all the courses with gerontology content, as well as for social workers and social work courses. They were not associated for nurses and nursing courses, however. Study results were disseminated to NGEC staff and board members, gerontology faculty and community agency administrators.

Norplant: nursing's responsibility in procreative rights.

PIP: Trained nurse practitioners can insert the contraceptive implant system Norplant. Courts may call on nurse practitioners to insert Norplant in poor women. Legislative and prosecutorial initiatives to coerce low-income women and female parolees to use contraceptives should not become law. Offering incentives to poor women is another form of involuntary fertility control. Eugenics and the sterilization campaign of the past form the basis for judicial and legislative initiatives to coerce women to accept Norplant. Providers have inserted Norplant in women from other countries without the women knowing the side effects. Often medical personnel do not remove Norplant when women request its removal. Nurses have historically played a public policy role in reproductive rights. They have promoted procreative rights through their roles as educators/counselors, advocators, empowerers, and practitioners. Nursing's power and expertise help protect against punitive government intrusion in reproductive rights and make sure that contraceptive breakthroughs (e.g., Norplant) strengthen procreative choices. They can guide the development of sound public policy. Norplant is not the answer to poverty, child abuse, or drug abuse. Nursing research can help policymakers become more responsive to the contraceptive and reproductive rights of everyone.^ieng

Inappropriate clinical care in nursing homes.

Using secondary data, an analysis was done of the prevalence of inappropriate clinical care among 3,149 Virginia Medicaid nursing home residents. Six types of inappropriate care were examined: the underprovision of skilled nursing care, physical rehabilitation and routine medical care; and the overuse of psychotropic drugs, physical restraints and urinary catheterization. Thirty-two (32) percent of the residents received inappropriate care in at least one care area and 7% received inappropriate care in two or more areas. Residents who received the most inappropriate care were more dependent in their activities of daily living, uncommunicative, incontinent, likely to have had a stroke, and less disruptive. Residents who received the most inappropriate care are among the most vulnerable residents, and stronger regulation and outside advocacy may be needed to protect them from inappropriate care.

Proximal femoral osteotomy using the AO fixed-angle blade plate.

We describe the technique and results of proximal femoral osteotomy performed with the AO fixed-angle blade plate in 157 hips of 101 pediatric patients. Postoperative immobilization or restriction of activity was not prescribed. Fourteen complications occurred in 11 patients. Use of preoperative antibiotics decreased the rate of infection from 12% to 0%, which was significant. All osteotomies healed by 16 weeks postoperatively with no nonunions, malunions, device failures, or avascular necrosis. Using no postoperative immobilization in these children was successful and resulted in few complications when the appropriate-sized blade plate was used.

Spinal fusion in Duchenne muscular dystrophy.

Sixty-eight patients from a clinical population of 183 patients with Duchenne muscular dystrophy underwent posterior spinal fusion with instrumentation for progressive spinal deformity. Pulmonary complications were the most common postoperative problem, occurring in 17 per cent of the patients. A 35 per cent normal forced vital capacity was a reliable indicator of pulmonary complication risk. The patients with surgically stabilized spines were more comfortable in the later years of life and easier to care for, but deteriorating pulmonary function was not affected by the spinal fusion. The average age at death for the 29 boys who underwent spinal fusion was 18.3 years, which was similar to that of the 58 boys with scoliosis. Factors that improved the patients' quality of life included segmental instrumentation, fusion from T2 to the pelvis, correcting or balancing scoliosis, creating normal sagittal plane alignment and correcting pelvic obliquity.