Citations

ABSTRACT Background The Accreditation Council for Graduate Medical Education requires residents to learn and demonstrate proficiency in practice improvement. Quality improvement (QI) projects are a way to improve patient care as well as facilitate education on this core competency. There are inherent barriers to completing these goals in the structure of residency training including rigorous resident schedules and a limited number of projects and resources. Objectives We developed a QI programme using an experiential class project and incorporated it into our Internal Medicine Resident Core Curriculum to improve the residents’ knowledge of QI methods. We assessed the residents’ experience, knowledge and interest in practice and QI subject matter with a survey preimplementation and postimplementation. Methods In 2009, 24 residents in the Internal Medicine resident programme completed a survey measuring their experience, knowledge and interest in QI initiatives. They then completed a QI 1-year programme, with monthly, 1-hour sessions combining didactics and a resident-designed project. At the conclusion of the year, the residents completed the same survey, and the results were compared and analysed. Results Postcurriculum questionnaires revealed residents were more knowledgeable about QI methods, showing improvement in knowledge about institutional-wide QI projects, better preparation for implementing a QI project, and more likely to participate in QI in the future. The project completed was one which improved patients’ knowledge of their anticipated date of discharge from the hospital. Conclusions A class quality project can teach QI to residents incorporating both didactic and practical methods to maximise the experience and minimise the barriers. We found that this method improved residents experience, knowledge and interest in quality initiatives.

1. If gastric acid is necessary for the absorption of dietary calcium, the total absence of gastric acid secretion that occurs in pernicious anaemia could result in bone loss. To investigate this, we measured calcium absorption and bone density in 21 postmenopausal women (ages 51–76 years) with pernicious anaemia and in 24 normal postmenopausal women (ages 51–79 years). 2. Relative to the normal women, in the women with pernicious anaemia the bone mineral density of the lumbar spine was decreased by 16% (P < 0.001). 3. After adjustment for age and body weight, lumbar spine bone mineral density correlated with the serum concentration of group 1 pepsinogens (a group of proteins produced by the gastric fundus) (r= 0.61, P < 0.01). 4. Despite achlorhydria, the women with pernicious anaemia had normal true fractional calcium absorption and normal serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D. 5. We conclude that gastric acid is not required for the absorption of dietary calcium. Thus, the loss of cancellous bone must be caused by some mechanism yet to be identified.

Objective: We conducted a systematic review to evaluate whether caregiver-involved interventions improve patient outcomes among adults with dementia or Alzheimer’s disease. Method: We identified and summarized data from randomized controlled trials enrolling adults with dementia or Alzheimer’s disease by searching MEDLINE, PsycINFO, and other sources. Patient outcomes included global quality of life, physical and cognitive functioning, depression/anxiety, symptom control and management, and health care utilization. Results: We identified 31 trials; 20 compared a caregiver intervention with usual care or usual care with promise of intervention at completion of study period. Fifteen compared one caregiver intervention with another individual or caregiver intervention (active control). Compared with usual care or active controls, caregiver-involved interventions had low to insufficient strength of evidence and did not consistently improve patient outcomes. Discussion: Evidence is insufficient to endorse use of most caregiver interventions to improve outcomes for patients with dementia or Alzheimer’s disease.

Objective To update a previously proposed prognostic scoring system that predicts risk of biochemical recurrence ( BCR ) after salvage radiation therapy ( SRT ) for recurrent prostate cancer when using additional patients and a PSA value of 0.2 ng/ mL and rising as the definition of BCR . Patients and Methods We included 577 patients who received SRT for a rising PSA after radical prostatectomy in this retrospective cohort study. Clinical, pathological, and SRT characteristics were evaluated for association with BCR using relative risks ( RR s) from multivariable Cox regression models. Results With a median follow‐up of 5.5 years after SRT , 354 patients (61%) experienced BCR . At 5 years after SRT , 40% of patients were free of BCR . Independent associations with BCR were identified for the PSA level before SRT ( RR [doubling]: 1.25, P < 0.001), pathological tumour stage ( RR [T3a vs T2] 1.21, P = 0.19; RR [T3b/T4 vs T2] 2.09, P < 0.001; overall P < 0.001), Gleason score ( RR [7 vs <7] 1.63, P < 0.001; RR [8–10 vs <7] 2.28, P < 0.001; overall P < 0.001), and surgical margin status ( RR [positive vs negative] 0.71, P = 0.003). We combined these four variables to create a prognostic scoring system that predicted BCR risk with a c ‐index of 0.66. Scores ranged from 0 to 7, and 5‐year freedom from BCR for different levels of the score was as follows: Score = 0–1: 66%, Score = 2: 46%, Score = 3: 28%, Score = 4: 19%, and Score = 5–7: 15%. Conclusion We developed a scoring system that provides an estimation of the risk of BCR after SRT . These findings will be useful for patients and physicians in decision making for radiation therapy in the salvage setting.

Purpose To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome. Patients and Methods A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided. Results When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor–positive, human epidermal growth factor receptor 2–nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death. Conclusion Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor–positive disease.

Significance Treg cells suppress excessive and aberrant immune responses. Impaired function or homeostasis of Treg cells would induce severe autoimmune and inflammatory diseases. Forkhead box P3 (FOXP3), as a master regulator of Treg cells, forms a large complex with other binding factors to modulate Treg-cell function subtly in pathological and physiological conditions. We identified that Deleted in breast cancer 1 (DBC1) is an essential subunit of the FOXP3 complex in human CD4 + Treg cells. Our results show that the inflammatory cytokines TNF-α or IL-6 trigger FOXP3 degradation, whereas downregulation of DBC1 expression prevents FOXP3 degradation and maintains Treg-cell function under inflammatory stimuli in vitro and in vivo. These findings unveil a previously unidentified pathway for therapeutically modulating FOXP3 + Treg-cell stability under inflammation.

Ketamine and lithium both inhibit glycogen synthase kinase 3. In addition, lithium and ketamine have synergistic antidepressant-like effects at individually subeffective doses in rodents. We hypothesized that ketamine’s antidepressant effects would be improved by therapeutic doses of lithium versus valproate and that serum lithium levels would positively correlate with ketamine’s antidepressant efficacy. Thirty-six patients with treatment-resistant bipolar depression maintained on therapeutic-dose lithium (n=23, 0.79 ± 0.15 mEq/L) or valproate (n=13, 79.6 ± 12.4 mg/mL) received 0.5 mg/kg ketamine infusion in a randomized, double-blind, placebo-controlled, crossover trial. The primary depression outcome measure—the Montgomery-Åsberg Depression Rating Scale (MADRS)—was assessed before infusion and at numerous postinfusion time points. Both lithium (F1,118= 152.08,p<0.001, andd=2.27) and valproate (F1,128= 20.12,p<0.001, andd=0.79) significantly improved depressive symptoms, but no statistically significant difference was observed between mood stabilizer groups (F1,28= 2.51,p=0.12, andd=0.60). Serum lithium and valproate levels did not correlate with ketamine’s antidepressant efficacy. Although the study was potentially underpowered, our results suggest that lithium may not potentiate ketamine’s antidepressant efficacy in treatment-resistant bipolar depression.

Background and purposeLow density lipoprotein receptor related proteins (LRPs) 1 and 6 have been implicated in cerebral ischaemia. In addition, genetic variation in LRP1 and LRP6 has been linked with various factors that are related to risk of ischaemic stroke. The aim of this study was to examine the association of LRP1 and LRP6 gene variants with risk of ischaemic stroke as part of the Ischemic Stroke Genetics Study (ISGS).MethodsA Caucasian series (434 stroke patients, 319 controls) and an African American series (161 stroke patients, 116 controls) were included. Fourteen LRP6 variants and three LRP1 variants were genotyped and assessed for association with ischaemic stroke.ResultsIn the Caucasian series, significant associations with ischaemic stroke were observed for LRP6 rs2075241 [odds ratio (OR) 0.42, P = 0.023], rs2302685 (OR 0.44, P = 0.049), rs7975614 (OR 0.07, P = 0.017), rs10492120 (OR 0.62, P = 0.036) and rs10743980 (OR 0.66, P = 0.037). Risk of ischaemic stroke was significantly lower for carriers of any of these five protective LRP6 variants (24.0% of subjects) compared to non‐carriers (OR 0.57, P = 0.003). The protective association for LRP6 rs2075241 was observed at a similar magnitude across ischaemic stroke subtypes, whilst the effects of rs23022685, rs10492120 and rs10743980 were most apparent for cardioembolic and large vessel stroke. In the African American series, LRP1 rs11172113 was associated with an increased risk of stroke (OR 1.89, P = 0.006).ConclusionsThe results of our preliminary study provide evidence that LRP6 and LRP1 variants may be associated with risk of ischaemic stroke. Validation in larger studies is warranted.