Autoinjector preference among patients with multiple sclerosis: results from a national survey.

PURPOSE: Autoinjectors are well-established in supporting multiple sclerosis (MS) therapy. This market survey was aimed at investigating patients' rating of three devices for subcutaneous interferon beta formulations: the electronic autoinjectors Betaconnect® and RebiSmart™ as well as the mechanical ExtaviPro™ device. PATIENTS AND METHODS: Organization and conduction of structured face-to-face interviews in five German cities were managed through an independent external market research company. After questionnaire validation (n=15), 85 participants currently either using the Betaconnect (n=39), the RebiSmart (n=36) or the ExtaviPro injector (n=10) were asked 22 questions in the same order. First, patients named their current device in use, watched the corresponding instruction video, and were queried about their device. Second, patients were asked about their opinion of an ideal autoinjector. Third, instruction videos for the two non-used devices were presented and participants could dummy-inject into a pillow. Last, patients evaluated device features and indicated their preferred autoinjector. RESULTS: Before having been presented the two other autoinjectors not in use, evaluation of patients' satisfaction with their own device revealed that 82% of the Betaconnect users, 67% of the RebiSmart and 60% of the ExtaviPro users were highly satisfied. All patients desired some improvement of their own device particularly concerning optimization of size and handling. Subsequent to testing and watching instruction videos of all devices, the Betaconnect received the best rating regarding different functions. Finally, participants indicated their preferred autoinjector, provided their own medication was suitable for all three devices: 56.5% of the participants (n=48/85) chose the Betaconnect, 36.5% the RebiSmart (n=31/85), and 5% the ExtaviPro device (n=4/85); 2% did not answer (n=2/85). CONCLUSION: In this survey, the Betaconnect device was the preferred autoinjector and may currently best meet patients' needs. As it was closest to participants' opinion of an ideal device, the Betaconnect might contribute to treatment adherence. Our results need to be confirmed in further studies.

Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV-1-infected patients treated with abacavir.

OBJECTIVES: The D:A:D study group reported a 1.9-fold increased relative risk (RR) of myocardial infarction (MI) associated with current or recent use of abacavir. The number needed to harm (NNH) incorporates information about the underlying risk of MI and the increased RR of MI in patients taking abacavir. METHODS: NNH was calculated as the reciprocal of the difference between the underlying risks of MI with and without abacavir use. A parametric statistical model was used to calculate the underlying risk of MI over 5 years. RESULTS: The relationship between NNH and underlying risk of MI is reciprocal, resulting in wide variation in the NNH with small changes in underlying risk of MI. The smallest changes in NNH are in the medium- and high-risk groups of MI. The NNH changes as risk components are modified; for example, for a patient who smokes and has a systolic blood pressure (sBP) of 160 mmHg and a 5-year risk of MI of 1.3% the NNH is 85, but the NNH increases to 277 if the patient is a nonsmoker and to 370 if sBP is within the normal range (120 mmHg). CONCLUSIONS: We have illustrated that the impact of abacavir use on risk of MI varies according to the underlying risk and it may be possible to increase considerably the NNH by decreasing the underlying risk of MI using standard of care interventions, such as smoking cessation or control of hypertension.

Quantitative MR imaging evaluation of the cartilage thickness and subchondral bone area in patients with ACL-reconstructions 7 years after surgery.

OBJECTIVE: To evaluate the cartilage thickness (ThC) and subchondral bone area (tAB) of the operated and contra-lateral non-operated (healthy) knees in patients with anterior cruciate ligament (ACL)-reconstruction 7 years after surgery using a quantitative and regional cartilage MR imaging (qMRI) technique. METHODS: Charts of 410 patients with ACL-reconstructions were retrospectively reviewed. Fifty-two patients (male/female, 28/24; mean age, 33.3 years) were included. Patients underwent KT-1000 testing and qMRI of both knees using coronal fat-saturated 3D spoiled gradient-recalled echo (SPGR) sequences (TR/TE, 44/4 ms) at 1.5 T. Quantitative analyses of ThC and tAB in the femoro-tibial cartilage plates were performed using a subregional approach. In addition, qualitative and quantitative assessment of femoral condyle shapes was performed. t tests with Bonferroni corrections were used for statistical analysis of side-to-side differences between the operated and non-operated knees. RESULTS: KT-1000 testing was abnormal in 3/52 patients (6%). Lateral femoral tAB was significantly lower (-9.2%), and medial tibial tAB was significantly larger (+2%) in the operated vs non-operated knee (P<0.001). Regional and subregional ThC side-to-side differences were less than 0.1mm and, except for the external lateral femoral subregion, they were not statistically significant. Flattened and broader shapes of medial femoral condyles (P<0.001) were found in operated knees. No significant association of presence of cartilage or meniscus lesions at surgery with ThC 7 years post-operatively was found (P=0.06-0.98). CONCLUSION: There is evidence for changes in the tAB and femoral shape 7 years post-ACL-reconstruction, but no side-to-side differences in subregional ThC were found between the operated and contra-lateral non-operated knees.

Automated CT-based analysis to detect changes in the prevalence of lytic bone metastases from breast cancer.

The spinal column is the most frequent site of bone metastasis in patients with breast cancer. It is important to understand how the pattern of vertebral lesions may be affected by the introduction of modern cancer therapies. The purpose of this study was to characterize changes in the radiological appearance of spinal column metastases over the past decade using highly automated Computed Tomography (CT) based computational analysis methods. Two case series studies were performed using CT scans of patients with confirmed spinal metastases secondary to breast cancer: Cohort A with CT scans acquired between 1998 and 2001 and Cohort B with CT scans acquired between 2004 and 2007. Diseased vertebrae were classified as lytic, blastic, or mixed based on CT scan intensity through an automated 3D computer algorithm. The relative incidence of lytic vertebral metastases decreased in comparing Cohort B to Cohort A (12% vs. 49%) with a corresponding increase in mixed lesions (51% vs. 18%) Significant associations were found between the percentage of lytic lesions in number of diseased vertebrae measured per patient and lack of bisphosphonate use (RR = 2.6) and for membership in Cohort A vs. Cohort B (RR = 5.9). This work highlights a change in the CT appearance of vertebral metastases from breast cancer during the past decade toward a lower proportion of lytic disease. Observation of patient therapies suggests that differences in radiological assessment may be linked, at least in part, to bisphosphonate use. These findings have important implications for both clinical practice and research strategies involving vertebral metastases.

A prospective study of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in adults with human immunodeficiency virus-1.

Antibody titres against Kaposi's sarcoma associated herpesvirus (KSHV or human herpesvirus 8 (HHV-8)) and Epstein-Barr virus (EBV) were examined in people who subsequently developed Kaposi's sarcoma and non-Hodgkin's lymphoma, within randomised controlled trials of antiretroviral therapy in adults infected with the human immunodeficiency virus-1 (HIV). For each case of Kaposi's sarcoma (n=189) and each case of non-Hodgkin's lymphoma (n=67), which developed after randomisation, one control was randomly selected from other trial participants, after matching for age, sex, ethnicity, mode of HIV transmission, type of treatment received and period of follow-up. Using sera taken an average of two and a half years before the diagnosis of cancer, titres of antibodies against KSHV latent (LANA) and lytic (K8.1) antigens and against EBV (VCA) antigens were investigated in relation to subsequent risks of cancer by calculating odds ratios (OR) using conditional logistic regression. Latent antibodies against KSHV were detectable among 38% (72 out of 189) of Kaposi's sarcoma cases and 12% (23 out of 189) of their controls (OR=4.4, 95% confidence intervals (CI) 2.3-8.3, P<0.001). The OR for Kaposi's sarcoma increased with increasing antilatent KSHV antibody titre (chi(2)(1) for trend=32.2, P<0.001). Lytic antibodies against KSHV were detectable among 33% (61 out of 187) of Kaposi's sarcoma cases and 19% (36 out of 187) of their controls (OR=2.0, 95% CI 1.2-3.4, P=0.003) and the OR for Kaposi's sarcoma increased with increasing antilytic KSHV antibody titre (chi(2)(1) for trend=6.2, P=0.02). Virtually, all cases and controls had anti-EBV antibodies detected and the OR for non-Hodgkin's lymphoma associated with a doubling of the anti-EBV antibody titre was estimated to increase by a multiplicative factor of 1.3 (95% CI 0.9-1.7, P=0.1). Kaposi's sarcoma was not associated with antibody levels against EBV (P=0.4) and non-Hodgkin's lymphoma was not associated with antibodies against KSHV (latent P=0.3; lytic P=0.5). Adjustment for CD4 count at the time of sample collection made no material difference to any of the results. In conclusion, among human immunodeficiency virus infected people, high levels of antibodies against KSHV latent and lytic antigens are strongly associated with subsequent risk of Kaposi's sarcoma but not non-Hodgkin's lymphoma. Antibody titre to EBV does not appear to be strongly associated with subsequent risk of Kaposi's sarcoma or non-Hodgkin's lymphoma in HIV infected people.

The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen.

OBJECTIVE: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts. METHODS: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20). RESULTS: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either. CONCLUSIONS: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen.

The effects of urethritis on seminal plasma HIV-1 RNA loads in homosexual men not receiving antiretroviral therapy.

OBJECTIVES: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting. METHODS: Prospective case-control study. HIV-1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV-1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks. RESULTS: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU. CONCLUSIONS: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world.

The effect of hospital type and surgical delay on mortality after surgery for hip fracture.

Death during the first year after hip fracture may be influenced by the type of hospital in which patients are treated as well as the time spent awaiting surgery. We studied 57,315 hip fracture patients who were admitted to hospital in Ontario, Canada. Patients treated in teaching hospitals had a decreased risk of in-hospital mortality (odds ratio (OR) 0.89; 95% confidence interval (CI) 0.83 to 0.97) compared with those treated in urban community institutions. There was a trend toward increased mortality in rural rather than urban community hospitals. In-hospital mortality increased as the surgical delay increased (OR 1.13; 95% CI 1.10 to 1.16) for a one-day delay and higher (OR 1.60; 95% CI 1.42 to 1.80) for delays of more than two days. This relationship was strongest for patients younger than 70 years of age and with no comorbidities but was independent of hospital status. Similar relationships were seen at three months and one year after surgery. This suggests that any delay to surgery for non-medical reasons is detrimental to a patient's outcome.

Lactic acidosis in HIV infected patients: a systematic review of published cases.

OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.

Autologous apoptotic T cells interact with dendritic cells, but do not affect their surface phenotype or their ability to induce recall immune responses.

Dendritic cells (DCs) play an important role in determining immunogenicity and the subsequent immune response. They may also have a role in maintaining peripheral tolerance to self-antigens by initiating an immune response only in the context of danger signals released from cells during stress, damage or death. These signals may originate from surrounding T cells as well as from other cells. Therefore, in this study the effect of autologous T cell injury on DC morphology and function has been investigated. Co-incubation of apoptotic or necrotic T cells with immature DCs altered their morphology towards a more mature appearance, with more cells showing activation as judged by spreading and formation of arborizing long processes. The apoptotic autologous T cells were rarely phagocytosed by immature DCs, compared to macrophages. The DC surface phenotype was not affected by the co-incubation with autologous injured T cells. The ability of DCs to elicit a secondary immune response was not altered by exposure to autologous injured T cells. These findings suggest that DC can continue to function in T cell activation, rather than in tolerogenic mode, even in the presence of large numbers of dying autologous T cells, such as may be present in the aftermath of an acute antiviral response.

Therapeutic vaccination (p24-VLP) of patients with advanced HIV-1 infection in the pre-HAART era does not alter CD4 cell decline.

In a randomized placebo controlled trial 304 HIV infected patients with CD4 cell counts below 350 cells/microL received therapeutic vaccination with: alum placebo (Group I, n = 102), p24-VLP 500 microg (Group II, n = 101) or p24-VLP 1000 microg (Group III, n = 101) p24-VLP monthly for six months. Over one year the average change in CD4 cell count did not differ significantly between groups (-32, -40 and -52 cells per microL respectively). There was also no difference between groups in progression to CDC category B or C events, or in adverse events. Therapeutic vaccination with p24-VLP does not affect CD4 cell decline in patients with advanced HIV infection.

The relation between hip fracture and alzheimer's disease in the canadian national population health survey health institutions data, 1994-1995. A cross-sectional study.

PURPOSE: The purpose of this study is to examine the relation between hip fractures and Alzheimer's disease in institutionalized men and women who participated in the 1994-1995 Canadian National Population Health Survey (NPHS).METHODS: Participants in the institutional component of NPHS were randomly chosen from selected health care institutions from all provinces in Canada. A questionnaire, which assessed health, demographic and socio-economic status, risk factors, medication use, and falls, was administered by an interviewer. Proxy respondents were sought for residents who were ill or incapacitated. Logistic regression was used to examine the association between hip fractures and Alzheimer's disease in 408 men and 1105 women >/=65 years. Models were examined with either hip fracture or Alzheimer's disease as the dependent variable. Covariates that were assessed included osteoporosis, age group, sex, medications, reported falls and comorbid conditions.RESULTS: All hip fractures reported in this survey were the result of a fall, however only 3.7% of falls resulted in a hip fracture. Those who had sustained a hip fracture were more likely to have Alzheimer's disease (OR 2.0, 95% CI 1.1-3.5), osteoporosis (OR 4.3, 95% CI 2.5-7.4) and heart disease (OR 2.4, 95% CI 1.1-5.0). Respondents who had Alzheimer's disease were more likely to have sustained a hip fracture (OR 2.1 95% CI 1.2-3.6), to have osteoporosis (OR 1.9, 95% CI 1.5-2.5), and to have fallen (OR 1.4, 95% CI 1.1-1.8) and were less likely to be taking anti-psychotic medication (OR 0.4, 95% CI 0.3-0.6) than those with no diagnosis of Alzheimer's disease.CONCLUSIONS: There is an association between Alzheimer's disease and hip fractures that is independent of other covariates in this representative sample of institutionalized elderly Canadians.

A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

The impact of excluding non-leisure energy expenditure on the relation between physical activity and mortality in women.

The purpose of this study was to examine the relation between physical activity and mortality in a 7-year follow-up of a sample of women more than 30 years of age (N = 6,620) from the Canada Fitness Survey cohort, which was initiated in 1981. Age-adjusted relative risks relating quartiles of average daily energy expenditure (kilocalories per kilogram of body weight per day) to mortality were estimated using logistic regression. Compared with the least active, the risk of all-cause mortality was 0.73 for those in the highest quartile (P for trend = 0.03). The associations were stronger for cardiovascular disease mortality (odds ratio = 0.51; P for trend = 0.01) and fatal myocardial infarction (odds ratio = 0.61; P for trend = 0.04) for those in the highest quartile. These relations were due mainly to the contribution of non-leisure (household chores) energy expenditure, which represented, on average, 82% of women's total activity. The accompanying study on the same cohort by Villeneuve et al reported estimates based on a subset of leisure-time physical activity only, which underestimates the activity of many women (Villeneuve PJ, Morrison HI, Craig CL, Schaubel DE. Physical activity, physical fitness, and risk of dying. Epidemiology 1998;9;632-635). The resulting bias illustrates the importance of including non-leisure energy expenditure in the assessment of total activity. These data support the hypothesis that physical activity is inversely associated with risk of death in women.

A study of the reliability of the Canada Fitness Survey questionnaire.

PURPOSE: The purposes of this study are to assess the reliability of the physical activity components of the Canada Fitness Survey (CFS) questionnaire (N = 64 males, N = 63 females) and the Canadian Aerobic Fitness Test (N = 44 males, N = 52 females) in a sample of subjects between 15 and 80 yr. RESULTS: The intraclass correlation (rI) for the fitness scores was 0.98. The activity variables showed low to moderate correlations (rI = 0.48-0.53). Correlations were higher for males (rI = 0.38-0.65) than females (rI = 0.28-0.60) for most of the activity variables reported. Males generally report leisure activity more reliably than nonleisure activity, whereas the opposite was true for females. Males reported strenuous activity with higher reliability (rI = 0.86) than females (rI = 0.31). There was considerable variation in the reliability of specific activities. Of the components of physical activity (time, intensity, duration) that comprise the energy expenditure (EE) variable, the least reliably reported is intensity for both males (rI = 0.43) and females (rI = 0.55). CONCLUSIONS: The CFS questionnaire is moderately reliable for most measures of physical activity. Estimates of reliability vary considerably among the various activities and components of these activities and between males and females.