A Bundle of Services Increased Ascertainment of Tuberculosis among HIV-Infected Individuals Enrolled in a HIV Cohort in Rural Sub-Saharan Africa.

OBJECTIVES To report on trends of tuberculosis ascertainment among HIV patients in a rural HIV cohort in Tanzania, and assessing the impact of a bundle of services implemented in December 2012, consisting of three components:(i)integration of HIV and tuberculosis services; (ii)GeneXpert for tuberculosis diagnosis; and (iii)electronic data collection. DESIGN Retrospective cohort study of patients enrolled in the Kilombero Ulanga Antiretroviral Cohort (KIULARCO), Tanzania.). METHODS HIV patients without prior history of tuberculosis enrolled in the KIULARCO cohort between 2005 and 2013 were included.Cox proportional hazard models were used to estimate rates and predictors of tuberculosis ascertainment. RESULTS Of 7114 HIV positive patients enrolled, 5123(72%) had no history of tuberculosis. Of these, 66% were female, median age was 38 years, median baseline CD4+ cell count was 243 cells/µl, and 43% had WHO clinical stage 3 or 4. During follow-up, 421 incident tuberculosis cases were notified with an estimated incidence of 3.6 per 100 person-years(p-y)[95% confidence interval(CI)3.26-3.97]. The incidence rate varied over time and increased significantly from 2.96 to 43.98 cases per 100 p-y after the introduction of the bundle of services in December 2012. Four independent predictors of tuberculosis ascertainment were identified:poor clinical condition at baseline (Hazard Ratio (HR) 3.89, 95% CI 2.87-5.28), WHO clinical stage 3 or 4 (HR 2.48, 95% CI 1.88-3.26), being antiretroviralnaïve (HR 2.97, 95% CI 2.25-3.94), and registration in 2013(HR 6.07, 95% CI 4.39-8.38). CONCLUSION The integration of tuberculosis and HIV services together with comprehensive electronic data collection and use of GeneXpert increased dramatically the ascertainment of tuberculosis in this rural African HIV cohort.

Adapting public agricultural extension services to climate change: Insights from Kenya

This paper analyses the adaptiveness of the Public Agricultural Extension Services (PAES) to climate change. Existing literature, interviews and group discussions among PAES actors in larger Makueni district, Kenya, provided the data for the analyses. The findings show that the PAES already have various elements of adaptiveness in its policies, approaches and methods of extension provision. However, the hierarchical structure of the PAES does not augur well for self-organisation at local levels of extension provision, especially under conditions of abrupt change which climate change might trigger. Most importantly, adpativeness presupposes adaptive capacity but the lack of resources in terms of funding for extension, limited mobility of extension officers, the low extension staff/farmer ratio, the aging of extension staff and significant dependence on donor funding limits the adaptiveness of the PAES. Accordingly criteria and indicators were identified in literature with which an initial assessement of the adaptiiveneess of PAES was conducted. However this assessment framework needs to be improved and future steps will integrate more specific inputs from actors in PAES in order to make the framework operational.

Firm-level strategic orientation and performance: a synthesis and extension of the knowledge base on entrepreneurial, market and learning orientation

Should a firm stay focused or should it rather adopt a broader strategic perspective? This dissertation summarizes and extends the existing knowledge base on entrepreneurial, market, and learning orientation. Building on multiple theoretical perspectives, empirical evidence from prior studies, as well as on survey and archival data collected in two economic contexts, performance effects from individual orientations, their dimensions and combinations are explored. Results reveal that the three strategic orientations are highly interrelated and that their relationship to firm performance is more complex than previously assumed.

Longitudinal extension of myelomalacia by intramedullary and subdural hemorrhage in a canine model of spinal cord injury

BACKGROUND CONTEXT In canine intervertebral disc (IVD) extrusion, a spontaneous animal model of spinal cord injury, hemorrhage is a consistent finding. In rodent models, hemorrhage might be involved in secondary tissue destruction by biochemical mechanisms. PURPOSE This study aimed to investigate a causal association between the extents of intramedullary, subdural and epidural hemorrhage and the severity of spinal cord damage following IVD extrusion in dogs. STUDY DESIGN/SETTING A retrospective study using histologic spinal cord sections from 83 dogs euthanized following IVD extrusion was carried out. METHODS The degree of hemorrhage (intramedullary, subdural, epidural), the degree of spinal cord damage in the epicenter (white and gray matter), and the longitudinal extent of myelomalacia were graded. Associations between the extent of hemorrhage and the degree of spinal cord damage were evaluated statistically. RESULTS Intramedullary and subdural hemorrhages were significantly associated with the degree of white (p<.001/ p=.004) and gray (both p<.001) matter damage, and with the longitudinal extension of myelomalacia (p<.001/p=.005). Intriguingly, accumulation of hemorrhagic cord debris inside or dorsal to a distended and ruptured central canal in segments distant to the epicenter of the lesion was observed exhibiting a wave-like pattern on longitudinal assessment. The occurrence of this debris accumulation was associated with high degrees of tissue destruction (all p<.001). CONCLUSIONS Tissue liquefaction and increased intramedullary pressure associated with hemorrhage are involved in the progression of spinal cord destruction in a canine model of spinal cord injury and ascending or descending myelomalacia. Functional and dynamic studies are needed to investigate this concept further.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study

UNLABELLED The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.

The impact of Medicare, Medicaid and Schip Extension Act of 2007 (MMSEA) on the long term acute care hospitals

The Long Term Acute Care Hospitals (LTACH), which serve medically complex patients, have grown tremendously in recent years, by expanding the number of Medicare patient admissions and thus increasing Medicare expenditures (Stark 2004). In an attempt to mitigate the rapid growth of the LTACHs and reduce related Medicare expenditures, Congress enacted Section 114 of P.L. 110-173 (§114) of the Medicare, Medicaid and SCHIP Extension Act (MMSEA) in December 29, 2007 to regulate the LTCAHs industry. MMSEA increased the medical necessity reviews for Medicare admissions, imposed a moratorium on new LTCAHs, and allowed the Centers for Medicare and Medicaid Services (CMS) to recoup Medicare overpayments for unnecessary admissions. ^ This study examines whether MMSEA impacted LTACH admissions, operating margins and efficiency. These objectives were analyzed by comparing LTACH data for 2008 (post MMSEA) and data for 2006-2007 (pre-MMSEA). Secondary data were utilized from the American Hospital Association (AHA) database and the American Hospital Directory (AHD).^ This is a longitudinal retrospective study with a total sample of 55 LTACHs, selected from 396 LTACHs facilities that were fully operational during the study period of 2006-2008. The results of the research found no statistically significant change in total Medicare admissions; instead there was a small but not statistically significant reduction of 5% in Medicare admissions for 2008 in comparison to those for 2006. A statistically significant decrease in mean operating margins was confirmed between the years 2006 and 2008. The LTACHs' Technical Efficiency (TE), as computed by Data Envelopment Analysis (DEA), showed significant decrease in efficiency over the same period. Thirteen of the 55 LTACHs in the sample (24%) in 2006 were calculated as “efficient” utilizing the DEA analysis. This dropped to 13% (7/55) in 2008. Longitudinally, the decrease in efficiency using the DEA extension technique (Malmquist Index or MI) indicated a deterioration of 10% in efficiency over the same period. Interestingly, however, when the sample was stratified into high efficient versus low efficient subgroups (approximately 25% in each group), a comparison of the MIs suggested a significant improvement in Efficiency Change (EC) for the least efficient (MI 0.92022) and reduction in efficiency for the most efficient LTACHs (MI = 1.38761) over same period. While a reduction in efficiency for the most efficient is unexpected, it is not particularly surprising, since efficiency measure can vary over time. An improvement in efficiency, however, for the least efficient should be expected as those LTACHs begin to manage expenses (and controllable resources) more carefully to offset the payment/reimbursement pressures on their margins from MMSEA.^

Extension of k-ratio methods to rank-based analyses

An extension of k-ratio multiple comparison methods to rank-based analyses is described. The new method is analogous to the Duncan-Godbold approximate k-ratio procedure for unequal sample sizes or correlated means. The close parallel of the new methods to the Duncan-Godbold approach is shown by demonstrating that they are based upon different parameterizations as starting points.^ A semi-parametric basis for the new methods is shown by starting from the Cox proportional hazards model, using Wald statistics. From there the log-rank and Gehan-Breslow-Wilcoxon methods may be seen as score statistic based methods.^ Simulations and analysis of a published data set are used to show the performance of the new methods. ^