Default mode network activity and white matter integrity in healthy middle-aged ApoE4 carriers

Alzheimer’s disease (AD) is most commonly detected during old age, but the underlying neuropathologic changes likely appear decades earlier, especially among patients possessing genetic risk factors, such as the isoform E4 of the apolipoprotein E (ApoE4). In this study, we used magnetic resonance imaging (MRI) to assess default mode network (DMN) connectivity in 22 ApoE4 non-carriers and 14 matched ApoE4 carriers as well as white matter fractional anisotropy (FA) in 15 ApoE4 non-carriers and 11 demographically matched ApoE4 carriers. Cognitive tests were also administered. All of the participants were middle-aged adults. The analysis revealed no cognitive or white matter FA differences between carriers and non-carriers. However, in DMN regions previously implicated in AD, we did detect decreased functional connectivity. Our findings suggest that functional MRI abnormalities may be detectable well before cognitive decline or white matter changes among individuals at increased genetic risk for AD.     

Lessons Learned From Managing a Prospective, Private Practice Joint Replacement Registry: A 25-year Experience

Background

In 1984, we developed a private practice joint replacement registry (JRR) to prospectively follow patients undergoing THA and TKA to assess clinical and radiographic outcomes, complications, and implant survival. Little has been reported in the literature regarding management of this type of database, and it is unclear whether and how the information can be useful for addressing longer-term questions.

Questions/purposes

We answered the following questions: (1) What is the rate of followup for THA and TKA in our JRR? (2) What factors affect followup? (3) How successful is this JRR model in capturing data and what areas of improvement are identified? And (4) what costs are associated with maintaining this JRR?

Methods

We collected clinical data on all 12,047 patients having primary THA and TKA since 1984. Clinical and radiographic data were collected at routine followup intervals and entered into a prospective database. We searched this database to assess the rate of successful followup and data collection and to compare the effect of patient variables on followup. Costs related to database management were evaluated.

Results

Followup was poor at every time interval after surgery, with a tendency for worsening over time. Patients with a complication and those younger than 70 years tended to followup with greater frequency. There were difficulties with data capture and substantial expenses related to managing the database.

Conclusions

Our findings highlight the difficulties in managing a JRR. Followup is poor and data collection is often incomplete. Newer technologies that allow easier tracking of patients and facilitate data capture may streamline this process and control costs.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-012-2541-y) contains supplementary material, which is available to authorized users.     

An open-label, sequential, dose-finding study of peginesatide for the maintenance treatment of anemia in chronic hemodialysis patients

ABSTRACT: BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. The primary objective of this phase 2 dose-finding study was to determine the once-monthly peginesatide dosing strategy that would maintain hemoglobin within [PLUS-MINUS SIGN]1.0 g/dL of baseline values after conversion from epoetin alfa; the safety of peginesatide was evaluated concurrently. METHODS: Chronic hemodialysis patients on stable regimens of epoetin alfa were sequentially assigned to cohorts that differed on (1) how the peginesatide starting dose was determined (using a single epoetin alfa--to-peginesatide dose conversion ratio or a tiered, weight-based or absolute-dose conversion table) and on (2) whether or not a 1-week erythropoiesis-stimulating agent-free interval was used. Peginesatide doses were titrated to maintain hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL from baseline. RESULTS: A total of 164 patients were enrolled and received intravenous peginesatide every 4 weeks for up to 6 doses; the duration of the study including follow-up was [LESS-THAN OR EQUAL TO]29 weeks. Overall, the proportion of patients with hemoglobin levels within [PLUS-MINUS SIGN]1.0 g/dL of baseline increased over the course of the study from 39% (Weeks 2--13) to 54% (Weeks 18--25). Cohorts that used tiered dose conversion tables trended towards having more stable peginesatide doses than did those cohorts that used a single dose conversion ratio. Moreover, cohorts that used an erythropoiesis-stimulating agent-free interval did not have the substantial initial increase in hemoglobin levels that was seen in those cohorts that did not use such an interval. In this study, the safety profile of peginesatide was consistent with those of marketed erythropoiesis-stimulating agents. CONCLUSIONS: The results of this study were used to guide the dosing regimens used subsequently in phase 3 studies. Once-monthly peginesatide is feasible in hemodialysis patients.Trial registrationClinicalTrials.gov registration: NCT00228449.     

Antihypertensive therapy versus alternative therapeutic options for prehypertension: an evidence-based approach

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) defines hypertension as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg. The JNC-7 defines 'prehypertension' to include systolic BP values between 120 and 139 mmHg and diastolic BP values between 80 and 89 mmHg. Individuals with blood pressure in the prehypertension range are clearly at increased risk of developing hypertension in the future and have an increased risk of cardiovascular morbidity and mortality, compared with those with normal BP. However, there is paucity of evidence to intervene in these patients. In this article we discuss an evidence-based approach to therapeutic options in patients with prehypertension.     

Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-Mycobacterium tuberculosis activity

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generated in situ from indenoquinoxaline and l-tryptophan and reacts with various substituted β-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C–C and three C–N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for their in vitro activity against Mycobacterium tuberculosis H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 μg mL⁻¹) to ethambutol against Mycobacterium tuberculosis H37Rv.

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel spiropyrrolidine tethered indole hybrids in excellent yields employing a one-pot multicomponent 1,3-dipolar cycloaddition strategy.     

Rare double fracture-dislocation of the thumb： a case report and review of the literature

Simultaneous fracture/dislocation of the thumb carpometacarpal (CMC)joint and dislocation of the metacarpophalangeal (MCP)joint is considered as a rare injury pattern.We report an unusual case of dorsa...     

Delivery of Predialysis Care in an Academic Referral Nephrology Practice

The purpose of this study was to obtain a detailed picture of the delivery of all aspects of pre-end stage renal disease (ESRD) care in an academic nephrology practice. The study consisted of a cross-sectional review of the charts of 111 patients with chronic kidney disease (CKD) (Creatinine > 1.5 mg/dL for males, Creatinine > 1.3 mg/dL for females) followed either in a private practice or a public hospital clinic. Charts were reviewed for evidence of a number of quality of care items including the degree of blood pressure control, the use of angiotensin II blockade, treatment of anemia, bone disease, and cardiovascular risk factors, as well as evidence of dialysis orientation and vascular access placement. Compared with previous published studies, this study shows encouraging trends towards better outcomes in at least two areas with evidence of improvement in hemoglobin levels, use of angiotensin II blockade, and degree of blood pressure control. However it also reveals many areas where care could be improved. This was particularly true in the areas of access placement, bone and mineral metabolism, and cardiovascular disease. It will be interesting to see whether the recent introduction of CKD guidelines by the National Kidney Foundation (NKF) and the associated educational initiatives for primary care physicians and nephrologists that are planned will further serve to improve the management of CKD patients in the years to come.