The aborted trial of semagacestat has led some to invoke unanticipated effects of γ‐secretase inhibition on formation of amyloid β. However, the many substrates for γ‐secretases and the varied biological effects of each of the resultant cleavage products make ascribing causality much more complex than that. Ann Neurol 2011

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Objective. To assess the effects of two different mixed-mode (mail and web survey) combinations on response rates, response times, and nonresponse bias in a sample of primary care and specialty internal medicine physicians. Data Sources/Study Setting. Primary data were collected from 500 physicians with an appointment in the Mayo Clinic Department of Medicine (DOM) between February and March 2005. Study Design. Physicians were randomly assigned to receive either an initial mailed survey evaluating the Electronic Medical Record (EMR) with a web survey follow-up to nonrespondents or its converse--an initial web survey followed by a mailed survey to nonrespondents. Response rates for each condition were calculated using standard formula. Response times were determined as well. Nonresponse bias was measured by comparing selected characteristics of survey respondents to similar characteristics in the full sample frame. In addition, the distributions of results on key outcome variables were compared overall and by data collection condition and phase. Principal Findings. Overall response rates were somewhat higher in the mail/web condition (70.5 percent) than in the web/mail condition (62.9 percent); differences were more pronounced before the mode switch prior to the mailing to nonrespondents. Median response time was 2 days faster in the web/mail condition than in the mail/web (median 5 5 and 7 days, respectively) but there was evidence of under-representation of specialist physicians and those who used the EMR a half a day or less each day in the web/mail condition before introduction of the mailed component. This did not translate into significant inconsistencies or differences in the distributions of key outcome variables, however. Conclusions. A methodology that uses an initial mailing of a self-administered form followed by a web survey to nonrespondents provides slightly higher response rates and a more representative sample than one that starts with web and ends with a mailed survey. However, if the length of the data collection period is limited and rapid response is important, perhaps the web survey followed by a mailed questionnaire is to be preferred. Key outcome variables appear to be unaffected by the data collection method.

LAP-IPAA is equivalent to open IPAA in terms of safety and feasibility. In addition, LAP-IPAA provides significant improvements in short-term recovery outcomes.

Background: Scant data exists regarding the burden of fatigue and constitutional symptoms in patients with myeloproliferative disorders (MPDs) (essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis with myeloid metaplasia (MMM)). Methods: An Internet based survey of MPD patients regarding clinical course, blood counts, constitutional symptoms, and fatigue (FACT-AN and Brief Fatigue Inventory (BFI)). Results: Patient Demographics: A total of 1179 MPD patients (median age 56; 41.4% male) internationally (76% USA: 50 states, 30 countries, 6 continents) responded to the survey. Self reported diagnoses were PV (35%), ET (26%), or MMM (39%). Clinical History: 1025 patients (87%) had undergone MPD therapy (drugs 70.5%, phlebotomy 44.1%, other 16%). Thrombosis (n=261, 22%), hemorrhage (N=272; 23%), and splenomegaly (N=478 (43%) were frequently reported. Blood tests (available in 917) showed 39% were anemic, 7% transfusion dependent. Symptoms: Fatigue, pruritus, night sweats and bone pain were present across the majority of MPD patients (see table). Additionally it was observed that these symptoms appeared with nearly equal frequency in PV as in MMM patients. However MMM patients displayed more advanced features (fevers, night sweats and weight loss). MPD Associated Constitutional Symptoms in 1179 Patients SYMPTOM PV (N=405) ET (N=304) MMM (N=456) MISSING (N=14) TOTAL (N=1179) P VALUE Fatigue 344 (84.9%) 220 (72.4%) 381 (83.6%) 7 945 (81.1%) <0.0001 Pruritus 265 (65.4%) 120 (39.5%) 228 (50.0%) 3 613 (52.6%) <0.0001 Night Sweats 199 (49.1%) 123 (40.5%) 254 (55.7%) 4 576 (49.4%) 0.0002 Bone Pain 174 (43.0%) 125 (41.1%) 214 (46.9%) 4 513 (44%) 0.2480 Fevers 53 (13.1%) 26 (8.6%) 81 (17.8%) 2 160 (13.7%) 0.0013 Weight Loss 39 (9.6%) 22 (7.2%) 93 (20.4%) 0 154 (13.2%) <0.0001 Spleen Pain 17 (4.2%) 27 (8.9%) 30 (6.6%) 4 74 (6.3%) <0.0001 Fatigue (82% MPD linked) was significantly increased across all MPD subtypes compared to published controls for both the BFI (P<0.0001) and Fact-An (P<0.0001). Additionally 69% curtail social activity because of fatigue, 35% need assistance with activities of daily living, and 11% reported MPD associated medical disability. Fatigue strongly correlated with multiple MPD disease features including: anemia, bone pain, constitutional symptoms, pruritus, splenic pain, smoking, thrombosis, and hemorrhagic events (all p<0.0001). Interestingly, even in “asymptomatic” MPD patients (those without anemia, splenomegaly, or thrombohemorrhagic complications) (n=279)) 24% (41% PV, 31% ET, 28% MMM) described significant fatigue worse than published controls. Conclusions: Fatigue and other constitutional symptoms are a significant burden to MPD patients, despite current therapies employed. Additionally fatigue is also a significant problem even in MPD patients lacking other advanced disease features. Clearly, direct attempts to improve fatigue (through pharmacologic and non-pharmacologic interventions) are necessary.

External hemipelvectomy has low mortality but high morbidity. Postoperative wound infection and flap necrosis are multifactorial events related to length and extent of operation. Level of vascular ligation strongly influenced flap necrosis rate for posterior flap hemipelvectomy.

Uncorrected preoperative atrial fibrillation in patients undergoing coronary artery bypass grafting is associated with increased late cardiac morbidity and mortality and poor long-term survival. These data support consideration of atrial fibrillation surgery at the time of coronary artery bypass grafting.

Measurable compromises in long-term bowel function and quality of life were observed after extended vs. segmental resections. The relative differences in patient-related outcomes should be deliberated against the clinical benefits of extended resection for the individual patient.