Plasticity of microvascular oxygenation control in rat fast-twitch muscle: effects of experimental creatine depletion

Aging, heart failure and diabetes each compromise the matching of O2 delivery (QO2)-to-metabolic requirements (O2 uptake, VO2) in skeletal muscle such that the O2 pressure driving blood-myocyte O2 flux (microvascular PO2, PmvO2) is reduced and contractile function impaired. In contrast, β-guanidinopropionic acid (β-GPA) treatment improves muscle contractile function, primarily in fast-twitch muscle (Moerland and Kushmerick, 1994). We tested the hypothesis that β-GPA (2% wt/BW in rat chow, 8 wk; n=14) would improve QO2-to-VO2 matching (elevated PmvO2) during contractions (4.5 V @ 1 Hz) in mixed (MG) and white (WG) portions of the gastrocnemius, both predominantly fast-twitch). Compared with control (CON), during contractions PmvO2 fell less following β-GPA (MG -54%, WG -26%, p<0.05), elevating steady-state PmvO2 (CON, MG: 10±2, WG: 9±1; β-GPA, MG 16±2, WG 18±2 mmHg, P<0.05). This reflected an increased QO2/VO2 ratio due primarily to a reduced VO2 in β-GPA muscles. It is likely that this adaptation helps facilitate the β-GPA-induced enhancement of contractile function in fast-twitch muscles

Client perceptions of the BreastScreen Australia remote radiology assessment model

Background Telehealth and teleradiology are increasingly used around the world to facilitate health care provision when the health care provider and clients are separated by distance. The BreastScreen Australia Remote Radiology Assessment Model (RRAM) is an initiative developed to address the challenges of inadequate access to a local radiological workforce in regional Australia. With the growth in telehealth innovations more broadly, the RRAM represents a departure from the traditional onsite model where a radiologist would be co-located with practice staff during assessment clinics. Understanding client satisfaction is an important consideration with new models. This article explores client perceptions of the RRAM including awareness, satisfaction with experiences, confidence in the quality of care being received, and preferences regarding models of service delivery. Methods Clients in four BreastScreen services across three Australian states and territories were invited to provide feedback on their experiences of the RRAM. Brief face-to-face interviews based on a survey were conducted at the conclusion of assessment clinic visits. Clients also provided feedback through surveys completed and returned by post, and online. Results 144 clients completed the survey regarding their experiences of the RRAM. The majority were aged between 50 and 59 years (55/144, 38.2%). Most had attended a BreastScreen service for either screening or assessment on a total of two to five occasions (85/142, 59.9%) in the past. Nearly all women who attended a RRAM clinic expressed satisfaction with their experience (142/143, 99.3%). Clients were aware that the radiologist was working from another location (131/143, 91.6%) and the majority believed there wouldn’t be any difference in the care they received between the RRAM and the onsite model (120/142, 84.5%). Clients generally had no particular preference for either the onsite or RRAM model of service delivery. Conclusions Clients’ high satisfaction with their clinic experiences, high confidence in care being received, and the majority having no preference for either the onsite or remote model indicates their acceptance of the RRAM. Client acceptance of the model supports continuation of the RRAM at these sites and expansion. Findings may inform future telehealth innovations where key health care team members are working remotely

A Cross-Sectional Study to Assess HPV Knowledge and HPV Vaccine Acceptability in Mali

Despite a high prevalence of oncogenic human papilloma virus (HPV) infection and cervical cancer mortality, HPV vaccination is not currently available in Mali. Knowledge of HPV and cervical cancer in Mali, and thereby vaccine readiness, may be limited. Research staff visited homes in a radial pattern from a central location to recruit adolescent females and males aged 12–17 years and men and women aged ≥18 years (N = 51) in a peri-urban village of Bamako, Mali. Participants took part in structured interviews assessing knowledge, attitudes, and practices related to HPV, cervical cancer, and HPV vaccination. We found low levels of HPV and cervical cancer knowledge. While only 2.0% of respondents knew that HPV is a sexually transmitted infection (STI), 100% said they would be willing to receive HPV vaccination and would like the HPV vaccine to be available in Mali. Moreover, 74.5% said they would vaccinate their child(ren) against HPV. Men were found to have significantly greater autonomy in the decision to vaccinate themselves than women and adolescents (p = 0.005), a potential barrier to be addressed by immunization campaigns. HPV vaccination would be highly acceptable if the vaccine became widely available in Bamako, Mali. This study demonstrates the need for a significant investment in health education if truly informed consent is to be obtained for HPV vaccination. Potential HPV vaccination campaigns should provide more information about HPV and the vaccine. Barriers to vaccination, including the significantly lower ability of the majority of the target population to autonomously decide to get vaccinated, must also be addressed in future HPV vaccine campaigns

Same-Day Physical Therapy Consults in an Outpatient Neuromuscular Disease Physician Clinic

Background: Team-based care has been shown to offer more comprehensive benefits to patients when compared to standard physician-based care alone in clinics for chronic conditions. However, apart from grant-funded multidisciplinary clinics, there are no reports on the usage of same-day physical therapy (PT) consults within a daily outpatient neuromuscular disease (NMD) physician clinic. Objective: To determine the impact of same-day PT consults at the University of Utah’s outpatient Clinical Neurosciences Center. Design: A qualitative assessment and survey of patient satisfaction. Methods: An eight question Health Insurance Portability and Accountability Act-compliant patient satisfaction survey using a 5-point Likert scale was administered. Demographic data and Press-Ganey Provider Satisfaction surveys were retrospectively collected from electronic medical records for patients receiving same-day PT encounters in the neuromuscular division over 1 year. Results: Mean (standard deviation) age was 54.22 (19.81) years for 134 patient encounters, median age was 60 years, with 76 male (57%) and 58 female (43%) patients. Mean Likert score for 61 self-reported patient satisfaction surveys for same-day PT consults was 4.87 (97.4%). Press-Ganey Provider Satisfaction scores improved from 89.9% (N=287) for the year prior to 90.8% (N=320) for the corresponding year (P=0.427). A total of 46 (75.4%) patients have either never before received PT care or never before received PT care for their NMD, 67.4% of whom were male. Conclusion: Same-day PT consults in an outpatient NMD physician clinic demonstrated excellent patient satisfaction and improved access to specialty care. This model could potentially be implemented in other academic medical centers to improve access to rehabilitation services for patients with NMD

PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections

The influence of body weight on the pulmonary oxygen uptake kinetics in pre-pubertal children during moderate- and heavy intensity treadmill exercise

To assess the influence of obesity on the oxygen uptake (V˙O2) kinetics of pre-pubertal children during moderate- and heavy intensity treadmill exercise. We hypothesised that obese (OB) children would demonstrate significantly slower V˙O2 kinetics than their normal weight (NW) counterparts during moderate- and heavy intensity exercise. 18 OB (9.8 ± 0.5 years; 24.1 ± 2.0 kg m2) and 19 NW (9.7 ± 0.5 years; 17.6 ± 1.0 kg m2) children completed a graded-exercise test to volitional exhaustion and two submaximal constant work rate treadmill tests at moderate (90 % gas exchange threshold) and heavy (∆40 %) exercise intensities. Bodyweight significantly influenced the V˙O2 kinetics during both moderate- and heavy exercise intensities (P < 0.05). During moderate intensity exercise, the phase II τ (OB: 30 ± 13 cf. NW: 22 ± 7 s), mean response time (MRT; OB: 35 ± 16 cf. NW: 25 ± 10 s), phase II gain (OB: 156 ± 21 cf. NW: 111 ± 18 mLO2 kg−1 km−1) and oxygen deficit (OB: 0.36 ± 0.11 cf. NW: 0.20 ± 0.06 L) were significantly higher in the OB children (all P < 0.05). During heavy intensity exercise, the τ (OB: 33 ± 9 cf. NW: 27 ± 6 s; P < 0.05) and phase II gain (OB: 212 ± 61 cf. NW: 163 ± 23 mLO2 kg−1 km−1; P < 0.05) were similarly higher in the OB children. A slow component was observed in all participants during heavy intensity exercise, but was not influenced by weight status. In conclusion, this study demonstrates that weight status significantly influences the dynamic V˙O2 response at the onset of treadmill exercise in children and highlights that the deleterious effects of being obese are already manifest pre-puberty

Factors Predicting Discordant Virological and Immunological Responses to Antiretroviral Therapy in HIV-1 Clade C Infected Zulu/Xhosa in South Africa

Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%–42%) and 83% (95% CI:79%–86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥200 cells/mm3 after 12 and ≥500 cells/mm3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age

Assisted partner notification services to augment HIV testing and linkage to care in Kenya: study protocol for a cluster randomized trial

Background: HIV case-finding and linkage to care are critical for control of HIV transmission. In Kenya, >50% of seropositive individuals are unaware of their status. Assisted partner notification is a public health strategy that provides HIV testing to individuals with sexual exposure to HIV and are at risk of infection and disease. This parallel, cluster-randomized controlled trial will evaluate the effectiveness, cost-effectiveness, and feasibility of implementing HIV assisted partner notification services at HIV testing sites (clusters) in Kenya. Methods/design Eighteen sites were selected among health facilities in Kenya with well-established, high-volume HIV testing programs, to reflect diverse communities and health-care settings. Restricted randomization was used to balance site characteristics between study arms (n = 9 per arm). Sixty individuals testing HIV positive (‘index partners’) will be enrolled per site (inclusion criteria: ≥18 years, positive HIV test at a study site, willing to disclose sexual partners, and never enrolled for HIV care; exclusion criteria: pregnancy or high risk of intimate partner violence). Index partners provide names and contact information for all sexual partners in the past 3 years. At intervention sites, study staff immediately contact sexual partners to notify them of exposure, offer HIV testing, and link to care if HIV seropositive. At control sites, passive partner referral is performed according to national guidelines, and assisted partner notification is delayed by 6 weeks. Primary outcomes, assessed 6 weeks after index partner enrollment and analyzed at the cluster level, are the number of partners accepting HIV testing and number of HIV infections diagnosed and linked to care per index partner. Secondary outcomes are the incremental cost-effectiveness of partner notification and the costs of identifying >1 partner per index case. Participants are closely monitored for adverse outcomes, particularly intimate partner violence. The study is unblinded due to practical limitations. Discussion This rigorously designed trial will inform policy decisions regarding implementation of HIV partner notification services in Kenya, with possible application to other parts of sub-Saharan Africa. Examination of effectiveness and cost-effectiveness in diverse settings will enable targeted application and define best practices. Trial registration ClinicalTrials.gov NCT01616420

Usability evaluation of a clinical decision support tool for osteoporosis disease management

<p>Abstract</p> <p>Background</p> <p>Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems. Although guidelines are available, patients are not receiving appropriate diagnostic testing or treatment. Findings from a systematic review of osteoporosis interventions and a series of focus groups were used to develop a functional multifaceted tool that can support clinical decision-making in osteoporosis disease management at the point of care. The objective of our study was to assess how well the prototype met functional goals and usability needs.</p> <p>Methods</p> <p>We conducted a usability study for each component of the tool--the Best Practice Recommendation Prompt (BestPROMPT), the Risk Assessment Questionnaire (RAQ), and the Customised Osteoporosis Education (COPE) sheet--using the framework described by Kushniruk and Patel. All studies consisted of one-on-one sessions with a moderator using a standardised worksheet. Sessions were audio- and video-taped and transcribed verbatim. Data analysis consisted of a combination of qualitative and quantitative analyses.</p> <p>Results</p> <p>In study 1, physicians liked that the BestPROMPT can provide customised recommendations based on risk factors identified from the RAQ. Barriers included lack of time to use the tool, the need to alter clinic workflow to enable point-of-care use, and that the tool may disrupt the real reason for the visit. In study 2, patients completed the RAQ in a mean of 6 minutes, 35 seconds. Of the 42 critical incidents, 60% were navigational and most occurred when the first nine participants were using the stylus pen; no critical incidents were observed with the last six participants that used the touch screen. Patients thought that the RAQ questions were easy to read and understand, but they found it difficult to initiate the questionnaire. Suggestions for improvement included improving aspects of the interface and navigation. The results of study 3 showed that most patients were able to understand and describe sections of the COPE sheet, and all considered discussing the information with their physicians. Suggestions for improvement included simplifying the language and improving the layout.</p> <p>Conclusions</p> <p>Findings from the three studies informed changes to the tool and confirmed the importance of usability testing on all end users to reduce errors, and as an important step in the development process of knowledge translation interventions.</p

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations