Outcome of surgical management of stress fractures in high demand individuals.

Stress fractures represent one-fifth of overuse injuries in sport. Successful healing of stress fractures in high demand individuals is important to prevent complications upon early return to activity. This article reviews the literature on outcomes of surgical management of stress fractures in high demand individuals. An online literature search was carried out for articles published up to and including January 2017. Twenty five papers were reviewed. In the majority of studies, no complications were reported, clinical and radiographic healing was achieved, and patients returned to their premorbid level of activity. Current literature suggests good outcomes after surgical management of stress fractures in high demand individuals, particularly those in whom conservative treatment has failed. Further studies comparing surgical techniques are necessary to demonstrate the most efficacious.

Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems.

Signaling downstream of receptor tyrosine kinases controls cell differentiation and survival. How signals from different receptors are integrated is, however, still poorly understood. In this work, we have identified Kidins220 (Kinase D interacting substrate of 220 kDa)/ARMS (Ankyrin repeat-rich membrane spanning) as a main player in the modulation of neurotrophin and vascular endothelial growth factor (VEGF) signaling in vivo, and a primary determinant for neuronal and cardiovascular development. Kidins220(-/-) embryos die at late stages of gestation, and show extensive cell death in the central and peripheral nervous systems. Primary neurons from Kidins220(-/-) mice exhibit reduced responsiveness to brain-derived neurotrophic factor, in terms of activation of mitogen-activated protein kinase signaling, neurite outgrowth and potentiation of excitatory postsynaptic currents. In addition, mice lacking Kidins220 display striking cardiovascular abnormalities, possibly due to impaired VEGF signaling. In support of this hypothesis, we demonstrate that Kidins220 constitutively interacts with VEGFR2. These findings, together with the data presented in the accompanying paper, indicate that Kidins220 mediates the integration of several growth factor receptor pathways during development, and mediates the activation of distinct downstream cascades according to the location and timing of stimulation.

Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice.

Despite substantial evidence regarding the benefits of combined use of inhaled corticosteroids and long-acting beta2-agonists in asthma, such evidence remains limited for chronic obstructive pulmonary disease (COPD). Observational data may provide an insight into the expected survival in clinical trials of fluticasone propionate (FP) and salmeterol in COPD. Newly physician-diagnosed COPD patients identified in primary care during 1990-1999 aged > or = 50 yrs, of both sexes and with regular prescriptions of respiratory drugs were identified in the UK General Practice Research Database. Three-year survival in 1,045 COPD patients treated with FP and salmeterol was compared with that in 3,620 COPD patients who regularly used other bronchodilators but not inhaled corticosteroids or long-acting beta2-agonists. Standard methods of survival analysis were used, including adjustment for possible confounders. Survival at year 3 was significantly greater in FP and/or salmeterol users (78.6%) than in the reference group (63.6%). After adjusting for confounders, the survival advantage observed was highest in combined users of FP and salmeterol (hazard ratio (HR) 0.48 (95% confidence interval 0.31-0.73)), followed by users of FP alone (HR 0.62 (0.45-0.85)) and regular users of salmeterol alone (HR 0.79 (0.58-1.07)) versus the reference group. Mortality decreased with increasing number of prescriptions of FP and/or salmeterol. In conclusion, regular use of fluticasone propionate alone or in combination with salmeterol is associated with increased survival of chronic obstructive pulmonary disease patients managed in primary care.

Cost-effectiveness of fluticasone propionate administered via metered-dose inhaler plus babyhaler spacer in the treatment of asthma in preschool-aged children.

STUDY OBJECTIVES: To evaluate the cost-effectiveness of inhaled fluticasone propionate (FP) in children aged 12 to 47 months with asthma symptoms. DESIGN: A retrospective economic analysis conducted from the perspective of the Danish health-care system, based on clinical data from a 12-week study. SETTING: Thirty-three outpatient centers in nine countries. PATIENTS: Two hundred thirty-seven children aged 12 to 47 months with documented history of recurrent wheeze or asthma symptoms. INTERVENTIONS: Two dosages of FP, 100 microg/d and 200 microg/d, and placebo administered in two divided doses via a metered-dose inhaler and a Babyhaler (Glaxo Wellcome; Middlesex, UK) spacer device. MEASUREMENTS: Effectiveness in terms of asthma exacerbations, control of cough and wheeze symptoms, symptom-free days, overall direct costs of asthma management in Danish kroner at 1999 prices, and mean and incremental cost-effectiveness ratios. RESULTS: FP, 200 microg/d, was significantly more effective than placebo treatment in terms of the proportion of exacerbation-free patients (73.7% vs 59.8%; p = 0.025) and patients experiencing a > or = 25% improvement in cough symptoms (57.9% vs 39.0%; p = 0.018). The costs per exacerbation-free patient, per patient with a > or = 25% improvement in cough and wheeze symptoms from baseline, and per symptom-free day were lower in the FP groups than in the placebo group. The incremental cost-effectiveness ratios for these end points indicated that the additional benefits of FP, 200 microg/d, were achieved at a lower overall cost compared with placebo treatment. CONCLUSIONS: From the perspective of the Danish health-care system, FP, 100 microg bid, administered via the Babyhaler inhalation device was cost-effective relative to standard therapy with bronchodilators alone.

Response of preschool children with asthma symptoms to fluticasone propionate.

BACKGROUND: Many uncertainties remain in the diagnosis and treatment of preschool children with asthma symptoms. OBJECTIVE: We sought to determine the subgroups of preschool children (aged 12-47 months) with recurrent asthma symptoms most likely to respond to inhaled fluticasone propionate (200 microg/d). METHODS: Subgroups of pooled data from 2 similar 12-week multicenter studies were analyzed. RESULTS: Children with frequent symptoms (symptoms on > or =3 days per week and a total of > or =75% days with symptoms during the 4-week run-in period; n = 169) showed a significantly greater increase in days without symptoms after fluticasone propionate treatment (0% to 45%) compared with after placebo treatment (0% to 25%, P =.005). Children with a family history of asthma (n = 213) also had a significantly greater increase in days without symptoms after fluticasone propionate (11% to 54%) compared with after placebo (7% to 35%, P =.002) and a significantly higher proportion of exacerbation-free patients (61% to 76%, P =.02). Children with less frequent symptoms, no family history of asthma, or both showed no significant treatment effect. There seemed to be no association between response to fluticasone propionate and history of rhinitis or eczema or the number of previous exacerbations. CONCLUSIONS: Children with frequent symptoms, a family history of asthma, or both showed the greatest response to fluticasone propionate treatment. These findings may help to predict treatment outcome and guide the management of preschool children with recurrent asthma symptoms.

Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects.

BACKGROUND: There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism. METHODS: This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500. Their mean age was 39 years, 67% were men, and all the women were premenopausal. RESULTS: The results of peripheral quantitative computed tomographic (pQCT) measurements (primary variable) showed that, compared with baseline values, there was no loss of trabecular or integral (cortical and trabecular) bone in the distal radius or tibia in any of the patients over the 12 month study period. No consistent pattern emerged from the analysis of changes from baseline in markers of bone formation and resorption after six and 12 months of treatment. CONCLUSION: The results of this study provide reassuring prospective one year data showing that inhaled corticosteroids, in the range of doses used, had no adverse effects on bone mass and metabolism in this group of asthmatic patients.

A randomized, double-blind study comparing the effects of beclomethasone and fluticasone on bone density over two years.

Cross-sectional studies have suggested that asthmatic patients receiving high dose inhaled corticosteroids and intermittent courses of oral corticosteroids have reduced bone mass. This prospective 2-yr study was undertaken to evaluate changes in bone density of patients receiving high doses of inhaled corticosteroids. Patients (n = 33) (males aged 18-50 yrs, females aged 18-40 yrs) on inhaled corticosteroids 1,000-2,000 microg x day(-1), were randomized in a double-blind fashion to either fluticasone propionate (FP) 1,000 microg x day(-1) or beclomethasone dipropionate (BDP) 2,000 microg x day(-1). In parallel, three open control groups of the same age range were studied: asthmatics (n = 8) receiving low dose inhaled corticosteroids (< or =400 microg x day(-1)) (group A); chronic, severe asthmatics (n = 8) receiving oral corticosteroids (> or =10 mg x day(-1) (group B); and healthy untreated volunteers (n = 7) (group C). Bone densitometry scans (quantitative computed tomography (QCT) of spine; dual X-ray absorptiometry of spine, femoral neck, and single photon absorptiometry of forearm) were performed at baseline and after 6, 12 and 24 months of treatment. Biochemical bone marker measurements (serum osteocalcin, bone alkaline phosphatase, pro-collagen type 1 carboxy terminal propeptide, deoxypyridinoline and C-telopeptide of type 1 collagen) were collected every 3 months. Fifteen FP (mean age 36 yrs, six male) and 9 BDP patients (mean age 33 yrs, five male); completed the study. At 0 months, mean bone mineral density (BMD) was lower in patients receiving inhaled corticosteroids (both low dose and high dose) than in normal volunteers. In the FP-treated group, mean vertebral trabecular BMD quantitative computed tomography remained stable with no evidence of decline, whereas there was some decline in the BDP-treated group. The treatment difference between FP and BDP was statistically significant in favour of FP for quantitative computed tomography measurements after 12 months (p = 0.006) and 24 months (p = 0.004). This study suggests that over 24 months, changes in bone density are minimal in patients on high-dose inhaled corticosteroids.

The effect of inhaled fluticasone propionate in the treatment of young asthmatic children: a dose comparison study.

The response in asthmatic young children to inhaled steroids within the usual pediatric dose range is unknown. We therefore evaluated the dose-related response in young children with moderate asthma to inhaled fluticasone propionate (FP) (delivered via the Babyhaler spacer device) within the pediatric dose range. A total of 237 children (mean age 28 mo, range 12 to 47) with moderate asthmatic symptoms were studied in this multicenter, randomized, double-blind, parallel group, placebo-controlled study of 12 wk treatment following a 4-wk run-in period. The median use of rescue medication was 1 dose in 2 d during the run-in period. FP 50 micrograms twice daily (FP100) and 100 micrograms twice daily (FP200) was compared with placebo inhaled from a pressurized metered-dose inhaler (pMDI) and the Babyhaler spacer device. With FP200 there was a statistically significant improvement from baseline, as compared with the placebo group, in 8 of 10 diary card parameters, including the three symptom domains of wheeze, cough, and breathlessness, and use of rescue medication. FP100 produced a significant reduction in 5 of these 10 parameters, whereas no significant differences were found between the FP200 and FP100. The numbers of patients with at least one exacerbation during treatment with placebo, FP100, and FP200 were 37%, 26%, and 20%, respectively. This difference between placebo and FP200, as well as the dose-related order was significant (p < 0.05). Both FP doses were as well tolerated as placebo over the 12 wk treatment with a similar incidence of adverse effects. Asthmatic symptoms in 1- to 3-yr-old children responded in a significant and dose-related manner to treatment with FP within a pediatric dose range.

Progression to AIDS or death following diagnosis with a class IV non-AIDS disease: utilization of a surveillance database.

Time to progression to an AIDS-defining disease or death was analyzed for residents of King County, Washington State, with selected class IV non-AIDS diagnoses. Relative to people with constitutional symptoms, the risk of progression to an AIDS-defining diagnosis was 1.4 [95% confidence interval (CI), 0.8-2.2), 1.6 (95% CI, 1.0-2.5), and 2.1 (95% CI, 1.3-3.5) times greater for people with a diagnosis of oral hairy leukoplakia, oral candidiasis, and multiple diseases, respectively. Relative to subjects with CD4 counts of > or = 200, the risk of progression to AIDS was greater for subjects with CD4 counts < 200; relative risks ranged from 2.3 (95% CI, 0.8-6.6) for subjects with constitutional symptoms and CD4 counts < 200 to 6.7 (95% CI, 3.3-13.6) for subjects diagnosed with oral hairy leukoplakia and CD4 counts > 200. However, the statistical test for interaction between CD4 count and diagnostic group was not significant (p = 0.62). Our findings are in general agreement with results from previous cohort studies and suggest the utility of surveillance databases for natural history studies of the course of HIV illness.

Survival after AIDS diagnosis in Washington State: trends through 1989 and effect of the case definition change of 1987.

Survival analysis was performed for AIDS cases diagnosed in Washington state from 1982 through 1989 and reported through October 31, 1991. No difference in survival time among diagnosis years 1987, 1988, and 1989 (p = 0.29) was found. Since September 1987, survival time was longest for cases with human immunodeficiency virus (HIV) wasting syndrome and HIV encephalopathy. Adjusted risk for death was significantly lower for these cases relative to all other cases (relative risk, 0.5; 95% confidence interval, 0.4-0.6). Explanations for the absence of continuing increase in survival time between 1987 and 1989 include changes in the frequency and timing of anti-HIV therapy. Longer survival time among cases diagnosed with HIV wasting or HIV encephalopathy is likely due to diagnosis earlier in the course of HIV disease. These results emphasize how changes over time in the definition of AIDS and evolving therapeutic standards may affect assessment of survival time when using surveillance data.

History of circumcision, medical conditions, and sexual activity and risk of penile cancer.

BACKGROUND: Epidemiological evidence suggests lack of neonatal circumcision as the strongest risk factor for penile cancer, but the role of sexually transmitted diseases in the etiology of penile cancer has remained unclear. PURPOSE: To further clarify risk factors for penile cancer, we examined the role of circumcision, personal characteristics and habits (such as smoking), sexually transmitted diseases, past sexual activity, and medical conditions of the penis. METHODS: A population-based, case-control study was conducted in western Washington state and in the province of British Columbia. We interviewed 110 men with penile cancer diagnosed from January 1979 to July 1990 and 355 control subjects from the general population, frequency matched to case subjects on age and date of diagnosis. Tumor tissue from 67 case subjects was tested for human papillomavirus (HPV) DNA by polymerase chain reaction. Results of blood tests from 69 case subjects and 208 control subjects were available for study. STATISTICALLY SIGNIFICANT RESULTS: Relative to men circumcised at birth, the risk for penile cancer was 3.2 times greater among men who were never circumcised and 3.0 times greater among men who were circumcised after the neonatal period. For current smokers, the risk was 2.8 times that of men who never smoked. The risk among men reporting a history of genital warts was 5.9 times that of men reporting no such history. Of 67 tumors tested for HPV DNA, 49% were positive; the majority of these positive tumors (70%) were type 16, which has been associated with anogenital carcinoma. Relative risks (RRs) associated with a reported history of penile rash or penile tear were 9.4 and 3.9, respectively. Among men not circumcised at birth, RRs associated with presence of smegma and difficulty in retracting the foreskin were 2.1 and 3.5, respectively. Twenty-eight percent of case subjects, compared with only 10% of control subjects, reported 30 or more sexual partners, and men with HPV-positive tumors were more likely to report a greater number of sexual partners. CONCLUSIONS: These results suggest that the absence of neonatal circumcision and potential resulting complications are associated with penile cancer. Additionally, medical conditions of the penis, sexual activity, infection with HPV, and smoking may increase the risk for penile cancer. IMPLICATIONS: A larger study would allow examination of interrelationships of circumcision, infection with HPV, and smoking as risk factors.

Effects of increasing outpatient diagnosis on AIDS surveillance.

Using AIDS surveillance data, we analyzed trends and correlates of outpatients AIDS diagnosis in Oregon and Washington. The proportion of outpatient diagnoses rose from 24% of cases in 1987 to 51% in 1990. Case characteristics associated with outpatient diagnosis included white race, urban residence, and the exposure category of male homosexual/bisexual contact. AIDS-defining conditions associated with outpatient diagnosis included Kaposi's sarcoma, HIV wasting syndrome, and esophageal candidiasis. Completeness and timeliness of reporting was poorer for cases diagnosed as outpatients compared with inpatients. As outpatient diagnosis becomes more common, modified surveillance methods may be needed to ensure complete case finding and consequent reliability of AIDS surveillance information.

Human papillomaviruses, herpes simplex viruses, and the risk of oral cancer in men.

A population-based case-control study was conducted in western Washington state to examine the relations between infection with human papilloma viruses (HPV), herpes simplex viruses (HSV), and risk of oral squamous cell cancer in men. Interviews were completed on 131 oral cancer cases diagnosed between January 1985 and December 1989 and 136 controls frequency matched to cases on age and date of diagnosis who were obtained by random digit dialing. The risk for oral cancer among men with 30 or more sexual partners was 2.4 times that of men with four or fewer partners (95% confidence interval (CI) 1.0-5.9). Men who ever practiced oral sex had lower risk for oral cancer relative to men who never practiced oral sex (relative risk (RR) = 0.4, 95% CI 0.2-0.8). Analyses of exfoliated oral cavity cells for the presence of HPV-6 DNA with polymerase chain reaction revealed that men with an oral HPV-6 infection had 2.9 times the risk for oral cancer of noninfected men (95% CI 1.1-7.3), whereas men with an oral HPV-16 infection had 6.2 times the risk for oral cancer of noninfected men (crude RR = 6.2, 95% CI 0.7-52.2). Relative risks associated with serologically detected HSV-1 and HSV-2 infections were 0.8 (95% CI 0.3-1.7) and 1.8 (95% CI 0.7-4.6), respectively. The authors conclude that HPV-6 is associated with oral cancer. Although men infected with HPV-16 and HSV-2 were at elevated risk, these associations may have been due to chance. The role of specific sexual practices in the transmission of viruses to the oral cavity remains unclear.

Low birth weight in relation to multiple induced abortions.

BACKGROUND: Most studies report that a single induced abortion does not increase risk for delivering a low birth weight infant in a subsequent pregnancy. However, the effect of multiple abortions has not been adequately evaluated. METHODS: This relationship was studied in 6541 White women who delivered their first child between 1984 and 1987. We compared the frequencies of low birth weight (less than 2500 g) among infants born to 1999 women without prior induced abortion and 1999 women with one abortion with the frequencies of low birth weight among infants born to women with two (n = 1850), three (n = 520), and four or more (n = 173) prior induced abortions. RESULTS: After adjustment for confounding variables, we found no linear relationship in risk of low birth weight among women with one (relative risk [RR] = 1.2, 95% confidence interval [CI] = 0.9-1.5), two (RR = 1.5, 95% CI = 1.1-2.0), three (RR = 1.3, 95% CI = 0.8-1.9), or four or more (RR = 1.6, 95% CI = 0.9-2.9) prior induced abortions. CONCLUSIONS: These findings confirm earlier reports of little or no evidence of harmful effects on birth weight by one or by two or more induced abortions. We further report that risk is not significantly elevated even in women with three, four, or more prior terminations of pregnancy when compared with women with one or two abortions.

Cigarette smoking and the risk of anogenital cancer.

The association between cigarette smoking and cervical cancer has been demonstrated in numerous prior studies. As part of population-based case-control studies of cancers of the vulva, vagina, cervix, anus, and penis in relation to infection with human papillomavirus, conducted in western Washington State and the province of British Columbia from the mid 1980s until the present time, the authors have collected detailed information on smoking history. The proportion of subjects who were current smokers of cigarettes ranged from slightly over 40% among incident cases of vaginal and cervical cancer to 60% among cases of vulvar and anal cancer. In contrast, only about 25% of controls were current smokers. The adjusted odds ratios (OR) associated with current smoking were substantially elevated (OR = 1.9-14.6) for all cancer sites except cancer of the vagina (OR = 1.3). The risks tended to increase in proportion to the number of cigarettes smoked. For most cancer sites, the odds ratios associated with former smoking were substantially less than those associated with current smoking and diminished with increasing time since cessation of smoking. The authors' data and those of other investigators suggest that cigarette smoking plays a role in the etiology of anogenital cancers and that smoking has a late-stage or promotional effect.

Human papillomavirus infection and anal cancer.

To study the association of human papillomavirus (HPV) infection with anal cancer, we examined tissue specimens from 126 patients with malignant lesions of the anal skin or mucosa. The patients were enrolled in a population-based, case-control study of ano-rectal cancer which is being conducted in the state of Washington and the Province of British Columbia. Histologic sections from formalin-fixed, paraffin-embedded tissues were tested for the presence of HPV DNA by in situ hybridization with biotin-labelled HPV 6, 11, 16, 18 and 31 DNA probes. HPV DNA sequences were found in tumor tissues from 24 of the 126 subjects (19.0%). When only squamous neoplasms are considered, 23 of 70 subjects (32.9%) had lesions which contained detectable HPV DNA. One HPV-positive patient had a cloacogenic carcinoma that contained regions of squamous differentiation and it was in these squamous cells that HPV DNA was localized. Of the 23 squamous lesions that harbored detectable HPV DNA, 8 contained HPV 6, 10 contained HPV 16, 1 contained HPV 18 and 4 contained an unclassified virus type(s). HPV DNA was found in tissues from 14 patients with carcinoma-in situ and 10 subjects with invasive carcinoma. These results demonstrate that some malignant tumors of the anus, in both men and women, are associated with HPV infection. We conclude that the anal squamous epithelium is another site where infection with the common genital tract HPVs may carry a risk of malignant transformation.

Sexual practices, sexually transmitted diseases, and the incidence of anal cancer.

To elucidate the risk factors for anal cancer, we interviewed and obtained blood specimens from 148 persons with anal cancer and from 166 controls with colon cancer in whom these diseases were diagnosed during 1978-1985. We found that in men, a history of receptive anal intercourse (related to homosexual behavior) was strongly associated with the occurrence of anal cancer (relative risk, 33.1; 95 percent confidence interval, 4.0 to 272.1). Anal intercourse was only weakly associated with the risk of anal cancer in women (relative risk, 1.8; 95 percent confidence interval, 0.7 to 4.2). Among the subjects with squamous-cell anal cancer, 47.1 percent of homosexual men, 28.6 percent of heterosexual men, and 28.3 percent of women gave a history of genital warts, as compared with only 1 to 2 percent of controls and no patients with transitional-cell anal cancer. In patients without a history of warts, anal cancer was associated with a history of gonorrhea in heterosexual men (relative risk, 17.2; 95 percent confidence interval, 2.0 to 149.4) and with seropositivity for herpes simplex type 2 (relative risk, 4.1; 95 percent confidence interval, 1.9 to 8.8) and Chlamydia trachomatis (relative risk, 2.3; 95 percent confidence interval, 1.1 to 4.8) in women. Current cigarette smoking was a substantial risk factor in both women (relative risk, 7.7; 95 percent confidence interval, 3.5 to 17.2) and men (relative risk, 9.4; 95 percent confidence interval, 2.3 to 38.5). We conclude that homosexual behavior in men is a risk factor for anal cancer, and that squamous-cell anal cancer is also associated with a history of genital warts, an association suggesting that papillomavirus infection is a cause of anal cancer. Certain other genital infections and cigarette smoking are also associated with anal cancer.

Cull rates of dairy cattle with antibodies to bovine leukemia virus.

The relationship of cull rate to age was investigated retrospectively in dairy cows with and without antibodies to bovine leukemia virus (BLV). Banked sera from eight annual herd tests on one 200-cow herd were tested for presence of BLV antibodies by agar-gel immunodiffusion using the Mr 51,000 glycoprotein antigen of BLV. Age-specific cull rates were computed for BLV-antibody-positive and antibody-negative cows yearly from 2 to 7 years of age. Cull rates, transformed by the Arc-sin square root, were analyzed by weighted regression. Transformed cull rates increased significantly as BLV-antibody-positive cows aged (one-tailed P = 0.023) but not as antibody-negative cows aged (one-tailed P = 0.59). A Mantel-Byar survival analysis showed significantly longer survival beyond 3.5 years of age among antibody-negative cows than among antibody-positive cows (P = 0.008).