The trouble with family medicine

BACKGROUND: The trouble with family medicine is that the perceptual framework it uses to view the phenomena of health and illness is at variance with the frameworks traditionally used by medicine generally. This creates difficulties in communication between those in family medicine and those in other disciplines, and sometimes leads to misunderstanding of the nature of the discipline of family medicine and its place in the health care system. Those who practise family medicine need to be 'multilingual', able to understand and speak the language and use the metaphors of family medicine, yet equally able to use the language and metaphors of other disciplines. OBJECTIVES: This paper, which begins with a clinical scenario, reviews the contemporary biomedical paradigm, proposes an alternative, and examines the conceptual frameworks which underpin the discipline of family medicine.      

Experience in adverse events detection in an emergency department: incidence and outcome of events

Objectives: The study was performed to determine the incidence, outcome and preventability of adverse events (AE) in an ED. Methods: The Quality in Australian Health Care Study methodology, modified to the ED, was utilized. Case histories of patients presenting to a tertiary hospital ED were screened for events. Events detected were classified, using a 104‐item data collection instrument, entered on Excel and analysed statistically using MINITAB. Results: A total of 5345 patients presented during the study period. Three thousand three hundred and thirty‐two patients completed full evaluation and comprised the study population. One hundred and ninety‐four events were detected. Except where specified, events with management causation ≤ 3 were excluded. This excluded 24 events (12.4%) leaving 170 for analysis. Of patients suffering an event, 53.5% occurred prior ED attendance, 41.7% of AE occurred within the ED, and 4.7% had contributions from both. The overall event rate, detected by the screening process, was 5.1%, with an incident rate of 1.98% and AE rate of 3.12%. The ED AE rate was 1.0%. If only those with management causation = 1 are excluded, then the overall event rate was 5.52%, with an AE rate of 3.33%. Fifty‐five per cent of events were judged to be preventable (preventability score ≥ 3). Events resulting in death and disability were more likely to be preventable (P ≤ 0.04). Conclusion: In conclusion, the Quality in Australian Health Care Study methodology has been utilized to provide data on incidents and AE in an ED.     

Successful learning of surgical liver anatomy in a computer-based teaching module

Aim

To analyze factors influencing the learning of surgical liver anatomy in a computer-based teaching module (TM).

Methods

Medical students in their third to fifth year of training (N \(=\) 410) participated in three randomized trials, each with a different primary hypothesis, comparing two- (2D) and three-dimensional (3D) presentation modes in a TM for surgical liver anatomy. Computed tomography images were presented according to the study and allocation group. Students had to answer eleven questions on surgical liver anatomy and four evaluative questions. Scores and time taken to answer the questions were automatically recorded. Since the three studies used the same 15 questions in the TM, a pooled analysis was performed to compare learning factors across studies.

Results

3D groups had higher scores (7.5 ± 1.7 vs. 5.6 ± 2.0; p < 0.001) and needed less time (503.5 ± 187.4 vs. 603.1 ± 246.7 s; p < 0.001) than 2D groups. Intensive training improved scores in 2D (p < 0.001). Men gave more correct answers than women, independent of presentation mode (7.2 ± 2.0 vs. 6.5 ± 2.1; p \(=\) 0.003). An overall association was found between having fun and higher scores in 11 anatomical questions (p < 0.001). In subgroup analysis, 3D groups had more fun than 2D groups (84.7 vs. 65.1 %; p < 0.001). If given the option, more students in the 2D groups (58.9 %) would have preferred a 3D presentation than students in the 3D group (35.9 %) would have preferred 2D (p  < 0.001).

Conclusion

3D was superior to 2D for learning of surgical liver anatomy. With training 2D showed similar results. Fun and gender were relevant factors for learning success.

     

G‐CSF Priming,clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia,advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm

Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G‐CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse‐free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m^?2 day^?1 × 5 and cytarabine at 2 g m^?2 day^?1 × 5 after G‐CSF priming in 50 newly‐diagnosed patients ages 18–64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64–88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71–93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well‐tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders. Am. J. Hematol. 90:295–300, 2015. © 2014 Wiley Periodicals, Inc.     

Natural killer cell precursors in the CD44neg/dim T-cell receptor population of mouse bone marrow

Natural killer (NK) cells develop from the nonadherent cell component of NK long-term bone marrow (BM) cultures (NK-LTBMC). Because these nonadherent cells are depleted of mature NK cells and T cells, but appear to enriched for NK precursors, they were used as a starting population to begin to define the NK precursors that function in NK- LTBMC. As the stromal cell component of NK-LTBMC has been shown to support interleukin (IL)-2-induced, CD44 dependent, NK cell development from nonadherent NK precursors, NK-LTBMC stroma was used in a limiting dilution assay (LDA) to quantitate the precursors. NK-LTBMC in 96-well plates were irradiated (20 Gy) to kill hematopoietic cells (including the NK precursors), seeded with limiting dilutions of the cells to be quantitated, cultured with 500 U/mL IL-2 for 13 days and assayed for development of NK activity by adding 51Cr-labeled YAC-1 cells to the wells and evaluating the release of 51Cr after 4 hours. Flow cytometric analysis, sorting, and quantitation of the nonadherent cell component of NK-LTBMC showed that NK precursors were concentrated in the CD44neg/dim subset that comprised 10% of the "lymphoid" gated cells. When the CD44neg/dim subset was sorted from BM of mice treated with 5- fluorouracil (5-FU) day before (-1FUBM), there were about 30% T cells, but no NK-1.1+ cells. When the T cells were removed by sorting and the CD44neg/dim, alphabeta, gammadelta T-cell receptorneg (TCR-) subpopulation was seeded onto irradiated stroma with IL-2, they proliferated, developed NK activity, became NK-1.1+ and CD44bright and remained alphabeta, gammadelta TCR-. The frequency of NK precursors in this population as estimated from the LDA was about 1/500.     

Diagnosis, management, and treatment of Alzheimer disease: a guide for the internist

Alzheimer disease (AD) is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies; however, there is no definitive diagnostic test for AD. Early recognition of AD allows time to plan for the future and to treat patients before marked deterioration occurs. Effective treatment requires monitoring of symptoms, functional impairment, and safety, and the use of multiple treatment modalities including pharmacotherapy, behavioral management, psychotherapies, psychosocial treatments, and support and education for families. Pharmacotherapeutic agents available for AD only provide symptomatic relief. The cholinesterase inhibitors, tacrine and donepezil, are effective in improving cognition, delaying nursing home placement, and improving behavioral complications in some patients. Other cholinesterase inhibitors are in development, as are other cholinomimetic agents such as muscarinic and nicotinic receptor agonists. Symptomatic treatments are available for the psychiatric manifestations of AD. Anti-inflammatories, antioxidants, neurotrophic factors, and other agents are promising new treatments for the future.     

Recombinant human interleukin-9 induces protein tyrosine phosphorylation and synergizes with steel factor to stimulate proliferation of the human factor-dependent cell line, M07e.

Human interleukin-9 (IL-9) was originally identified and cloned based on its stimulatory effect on proliferation of human myeloid cell line, M07e. IL-9 synergized with Steel factor, the ligand for the c-kit product, to stimulate M07e cell proliferation. To investigate potential mechanisms for this, IL-9 was assessed for effects on protein tyrosine kinase activities in M07e cells by immunoblotting with anti-phosphotyrosine monoclonal antibody; results were compared with those of Steel factor alone and in combination with IL-9, and those of 12-0-tetradecanoyl phorbol-13-acetate (TPA). Recombinant human IL-9 (10 ng/mL) rapidly and transiently induced or enhanced at least four tyrosine phosphorylated protein bands with molecular weights of 105, 97, 85, and 81 Kd. This tyrosine phosphorylation pattern was different from that generated by recombinant murine Steel factor or TPA stimulation and the combination of IL-9 and Steel factor did not change the IL-9-induced pattern. IL-9-induced tyrosine phosphorylated bands were completely blocked by treatment of IL-9 with anti-IL-9 antibody under conditions that also neutralized the synergistic effect of IL-9 with Steel factor on M07e cell proliferation. Genistein, a tyrosine kinase inhibitor, blocked phosphorylation of IL-9 and Steel factor-induced bands. Unlike Steel factor or TPA, IL-9 did not appear to stimulate phosphorylation of 42-Kd mitogen-activated protein (MAP) kinase or Raf-1, or enhance MAP kinase activity. MAP kinase and Raf-1 are serine/threonine kinases that are phosphorylated and activated by many growth factors and by agonists for protein kinase C. While the combination of IL-9 plus SLF did not appear to induce phosphorylation of new bands not already seen with either IL-9 or SLF alone, or enhance the phosphorylation of those bands seen with either cytokine alone, the results suggest that IL-9 activates specific and unique signal transduction pathways.