Weight Change and Glycemic Control After Diagnosis of Type 2 Diabetes

BACKGROUND  Limited community-based data describe weight change after diabetes diagnosis. OBJECTIVE  To evaluate weight change patterns and associations in the 1st year after diabetes mellitus type 2 diagnosis. DESIGN  Retrospective cohort study. PARTICIPANTS  Patients aged 21–75 with diabetes mellitus type 2 diagnosed between 1 January 1997 and 31 December 2004, identified from electronic medical records in Kaiser Permanente Northwest, a health maintenance organization. Eligible patients met weight measurement criteria (a baseline and three additional weight measurements) and did not have a condition associated with unintentional weight change (n = 4,135). MEASUREMENTS  We estimated 12-month patient weight trajectories using growth curve analyses, grouped similar trajectories using cluster analysis, and compared characteristics among groups. RESULTS  The four weight trajectory groups were “higher stable weight” (n = 757; 18.3%), “lower stable weight” (n = 2,236; 54.1%), “weight gain” (n = 664; 16.0%), and “weight loss” (n = 478; 11.6%). After adjustments, members of the weight-loss group were more likely than those in the weight-gain group to be older, female, take fewer medications, have had nutritionist visits, and have a lower mean HbA_1c. Those in the weight-loss group were less likely to be in a race group at higher risk for obesity, have depression or dyslipidemia, or have taken >30 days of a sulfonylurea alone or with metformin. CONCLUSIONS  A small-but-substantial group of patients had a mean weight trajectory that included a clinically significant weight loss. Weight-loss trajectories were strongly associated with better glycemic control when compared to weight gain. Patients with certain characteristics may need more support for weight loss. This study was supported by grant no. R21 DK073546–02 (Weight in Secondary Prevention) from the National Institute of Diabetes and Digestive and Kidney Diseases     

Sensitivity and Specificity of MMPI-2 Validity Scales and Indicators to Malingered Neurocognitive Dysfunction in Traumatic Brain Injury

The present study used a known-groups design to determine the classification accuracy of 10 MMPI-2 validity scales and indicators in the detection of cognitive malingering in traumatic brain injury. Participants were 259 traumatic brain injury and 133 general clinical patients seen for neuropsychological evaluation. The TBI patients were subdivided into groups based on a comprehensive examination of effort following Slick, Sherman, and Iverson's (1999 Slick , D. J. , Sherman , E. M. S. , & Iverson , G. L. ( 1999 ). Diagnostic criteria for malingering neurocognitive dysfunction: Proposed standards for clinical practice and research . The Clinical Neuropsychologist , 13 , 545 – 561 . [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) criteria. More extreme scores demonstrated excellent specificity; often impressive sensitivity was seen even while maintaining a low false positive error rate. Specificity was good even in stroke, memory disorder, and psychiatric patients without incentive. The results of this study are presented in frequency tables that can be easily referenced in clinical practice.     

Detecting Malingering in Traumatic Brain Injury and Chronic Pain: A Comparison of Three Forced-Choice Symptom Validity Tests

Individual and joint malingering detection accuracy of the Portland Digit Recognition Test (PDRT), Test of Memory Malingering (TOMM), and Word Memory Test (WMT) was examined in traumatic brain injury (TBI; 43 non-malingering, 27 malingering) and chronic pain (CP; 42 non-malingering, 58 malingering) using a known-groups design. At published cutoffs, the PDRT and TOMM were very specific but failed to detect about 50% of malingerers; the WMT was sensitive but prone to false positive errors. ROC analyses demonstrated comparable accuracy across all three tests. Joint classification accuracy was superior to that of the individual tests. Clinical and research implications are discussed.     

Features of extramedullary myeloma relapse: high proliferation, minimal marrow involvement, adverse cytogenetics: a retrospective single-center study of 24 cases

Extramedullary (e) relapse in multiple myeloma(MM) has an adverse prognosis, but knowledge concerning biological features and preferred treatment is scarce. We screened the myeloma registry of our institution for eMM relapses and identified 24 cases among 357 patients (pts).Only 8% of eMM relapses occurred after initial therapy, but 54% occurred after third-line or subsequent therapy. Baseline molecular cytogenetics revealed high-risk features in 10 of 19 evaluable patients. Most frequently, eMM presented as soft tissue (67%) and organ involvement (25%) or malignant effusion (12.5%). Incidence of leptomeningeal/CNS involvement was 21%. At eMM relapse, bone marrow infiltration was absent in 46% and low in 21%. Ten eMM biopsies were available showing increased proliferation, i.e., Ki-67 of 67%(range, 30–90%) of all cancer cells. Pts received radiation therapy, dose-intense chemotherapy, novel agents, and allogeneic SCT resulting in an overall response rate of 54%. Median progression-free survival was 2 (95% CI 0.08–3.92) and median overall survival 7 months (95% CI 3.56–10.43), respectively,with only three patients being alive at 12 months from diagnosis. EMM relapse may present at any anatomical site with frequent CNS involvement. Biological features include increased proliferation and low rate of marrow involvement.Prognosis remains poor despite intensive treatment.     

Sloths host Anhanga virus‐related phleboviruses across large distances in time and space

Sloths are genetically and physiologically divergent mammals. Phleboviruses are major arthropod‐borne viruses (arboviruses) causing disease in humans and other animals globally. Sloths host arboviruses, but virus detections are scarce. A phlebovirus termed Anhanga virus (ANHV) was isolated from a Brazilian Linnaeus's two‐toed sloth (Choloepus didactylus) in 1962. Here, we investigated the presence of phleboviruses in sera sampled in 2014 from 74 Hoffmann's two‐toed (Choloepus hoffmanni, n = 65) and three‐toed (Bradypus variegatus, n = 9) sloths in Costa Rica by broadly reactive RT‐PCR. A clinically healthy adult Hoffmann's two‐toed sloth was infected with a phlebovirus. Viral load in this animal was high at 8.5 × 10⁷ RNA copies/ml. The full coding sequence of the virus was determined by deep sequencing. Phylogenetic analyses and sequence distance comparisons revealed that the new sloth virus, likely representing a new phlebovirus species, provisionally named Penshurt virus (PEHV), was most closely related to ANHV, with amino acid identities of 93.1%, 84.6%, 94.7% and 89.0% in the translated L, M, N and NSs genes, respectively. Significantly more non‐synonymous mutations relative to ANHV occurred in the M gene encoding the viral glycoproteins and in the NSs gene encoding a putative interferon antagonist compared to L and N genes. This was compatible with viral adaptation to different sloth species and with micro‐evolutionary processes associated with immune evasion during the genealogy of sloth‐associated phleboviruses. However, gene‐wide mean dN/dS ratios were low at 0.02–0.15 and no sites showed significant evidence for positive selection, pointing to comparable selection pressures within sloth‐associated viruses and genetically related phleboviruses infecting hosts other than sloths. The detection of a new phlebovirus closely‐related to ANHV, in sloths from Costa Rica fifty years after and more than 3,000 km away from the isolation of ANHV confirmed the host associations of ANHV‐related phleboviruses with the two extant species of two‐toed sloths.     

Management of Urologic Complications in Renal Transplantation: A Single-Center Experience

Introduction

Ureterovesical complications subsequent to renal transplantation are associated with a high morbidity leading to graft loss or even death. In the present study, the management of these complications by using interventional and surgical procedures (native pyeloureterostomy [NPUS]/ureteroureterostomy [NUU] vs ureteroneocystostomy [UNC]) was evaluated retrospectively.

Patients and Methods

Between 1994 and 2012, a total of 780 kidney transplantations (690 deceased and 90 living donors) were performed at our institution. Demographic, clinical, and laboratory data from patients with urologic complications were analyzed and compared.

Results

Fifty patients (6.4%) exhibited ureterovesical complications, and 18 patients (36%) were operated on immediately. In 32 (64%) of 50 patients, an interventional procedure was initially performed, with 21 patients (66%) undergoing operation due to therapy failure. NPUS/NUU and UNC were performed in 26 (66.6%) and 13 (33.3%) patients, respectively. Indications for an operation were ureteral stenosis in 12 patients (30.8%), ureteral necrosis and urine leakage in 19 patients (48.7%), and symptomatic vesicoureteral reflux in 8 patients (20.5%). Long-term results were comparable between all groups.

Conclusions

Surgical revision of ureteral complications should be the standard therapy. NPUS/NUU, UNC, and the successful interventional procedures did not differ significantly in terms of long-term results.     

Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as Potent and Selective Pim-1 Inhibitors

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The stories they tell: How third year medical students portray patients,family members,physicians, and themselves in difficult encounters

Background: Physicians have long had patients whom they have labeled “difficult”, but little is known about how medical students perceive difficult encounters with patients.

Methods: In this study, we analyzed 134 third year medical students’ reflective essays written over an 18-month period about difficult student–patient encounters. We used a qualitative computerized software program, Atlas.ti to analyze students’ observations and reflections.

Results: Main findings include that students described patients who were angry and upset; noncompliant with treatment plans; discussed “nonmedical” problems; fearful, worried, withdrawn, or “disinterested” in their health. Students often described themselves as anxious, uncertain, confused, and frustrated. Nevertheless, they saw themselves behaving in empathic and patient-centered ways while also taking refuge in “standard” behaviors not necessarily appropriate to the circumstances. Students rarely mentioned receiving guidance from attendings regarding how to manage these challenging interactions.

Conclusions: These third-year medical students recognized the importance of behaving empathically in difficult situations and often did so. However, they often felt overwhelmed and frustrated, resorting to more reductive behaviors that did not match the needs of the patient. Students need more guidance from attending physicians in order to approach difficult interactions with specific problem-solving skills while maintaining an empathic, patient-centered context.     

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long‐term follow‐up

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high‐dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long‐term follow‐up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP‐MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy‐proven IgAN and treated with CyP. Thirty‐one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow‐up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from ?0·4 ml/min to ?0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2–17·8), with CyP‐MPA 10·7 years (range = 8·3–13·1), with IVIg 4·7 years (range = 2·6–6·6), and in untreated patients 1·2 years (range = 0·8–1·6; log‐rank test P < 0·01). In patients with progressive IgAN, our long‐term follow‐up observation indicates that sequential CyP‐MPA therapy maintains renal survival significantly.