Advances in clinical trials methodology: Intervention optimization approaches in emergency medicine.

The classical two-arm randomized clinical trial (RCT) is designed to test the efficacy or effectiveness of an intervention, which may consist of one or more components. However, this approach does not enable the investigator to obtain information that is important in intervention development, such as which individual components of the intervention are efficacious, which are not and possibly should be removed, and whether any components interact. The Multiphase Optimization Strategy (MOST) is a new framework for development, optimization, and evaluation of interventions. MOST includes the RCT for purposes of evaluation, but inserts a phase of research before the RCT aimed at intervention optimization. The optimization phase requires one or more separate trials similar in scope to an RCT, but employing a different experimental design. The design of the optimization trial is selected strategically so as to maximize the amount of scientific information gained using the available resources. One consideration in selecting this experimental design is the type of intervention to be optimized. If a fixed intervention, i.e. one in which the same intervention content and intensity is provided to all participants, is to be optimized, a factorial experiment is often appropriate. If an adaptive intervention, i.e. one in which intervention content or intensity is varied in a principled manner, is to be optimized, a sequential multiple-assignment randomized trial (SMART) is often a good choice. The objective of this article is to describe MOST and the scientific rationale for its use; describe two current applications of MOST in emergency medicine research, one using a factorial experiment and the other using a SMART; and discuss funding strategies and potential future applications in studying the care of individuals with acute illness, injury, or behavioral disorders.

Breast Cancer Knowledge and Decisions Made for Contralateral Prophylactic Mastectomy: A Survey of Surgeons and Women in the General Population.

BACKGROUND: Decisions made to undergo contralateral prophylactic mastectomy, in women at low risk for bilateral disease, are often attributed to a lack of knowledge. This study examines the role knowledge plays in determining surgical treatment for unilateral breast cancer made by laywomen and surgeons for themselves or loved ones. METHODS: The study cohort had three groups: (1) laywomen in the general population, (2) breast surgeons, and (3) plastic surgeons. Laywomen were recruited using Amazon Mechanical Turk Crowd Sourcing. Breast and plastic surgeons from nine states were sent electronic surveys. Demographic and contralateral prophylactic mastectomy-specific data on decisions and knowledge were collected and analyzed. RESULTS: Surveys from 1333 laywomen, 198 plastic surgeons, and 142 breast surgeons were analyzed. A significantly greater proportion of laywomen in the general population favored contralateral prophylactic mastectomy (67 percent) relative to plastic (50 percent) and breast surgeons (26 percent) (p < 0.0001). Breast surgeons who chose contralateral prophylactic mastectomy were younger (p = 0.044) and female (0.012). On assessment of knowledge, 78 percent of laywomen had a low level of breast cancer knowledge. Laywomen with higher levels of breast cancer knowledge had lower odds of choosing contralateral prophylactic mastectomy (OR, 0.37; 95 percent CI, 0.28 to 0.49). CONCLUSIONS: Fewer women are likely to make decisions in favor of contralateral prophylactic mastectomy with better breast cancer-specific education. A knowledge gap likely explains the lower rates with which surgeons choose contralateral prophylactic mastectomy for themselves or loved ones; however, some surgeons who were predominantly young and female favor contralateral prophylactic mastectomy. Improving patient education on surgical options for breast cancer treatment is critical, with well-informed decisions as the goal.

Reduced intensity vs. myeloablative conditioning with fludarabine and PK-guided busulfan in allogeneic stem cell transplantation for patients with AML/MDS.

Conditioning regimens contribute significantly to outcomes following allogeneic stem cell transplantation (allo-SCT). Reduced-intensity conditioning (RIC) regimens provide lower toxicity at the cost of reduced efficacy compared with myeloablative conditioning (MAC) regimens. However, because pre-transplant prognostic variables often determine the conditioning regimen, studies of RIC vs. MAC have been inconclusive. We present a retrospective analysis of 242 acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) patients, 112 of whom were in 56 pairs matched using propensity scores, to account for variation that may confound clinical outcomes. The uniform conditioning regimens consisted of fludarabine with pharmacokinetic (PK)-guided intravenous busulfan (Bu). The RIC and MAC regimens were dosed at the average daily area under the concentration-vs-time curve (AUC) of 4000 µMol min and 5000-6000 µMol min, or total course AUC of 16,000 µMol min and 20,000-24,000 µMol min, respectively; PK-guided dosing removes overlap in systemic Bu exposure. When patients' data were propensity-matched, there was a trend toward significantly increased full donor chimerism and decreased chronic graft vs. host disease in RIC, and no significant differences in progression free survival and overall survival between RIC and MAC. Our results also elucidate the efficacy of PK-guided-dosing in the setting of allo-SCT for AML and MDS.

Complications in body contouring stratified according to weight loss method.

BACKGROUND: Body contouring procedures following massive weight loss have become increasingly common and, unfortunately, continue to be associated with a high complication rate. OBJECTIVE: To evaluate how weight loss method affects complications following abdominally based body contouring procedures. METHODS: Patients undergoing abdominally based contouring procedures were retrospectively evaluated over an 11-year period and stratified into two groups based on method of weight loss: diet and exercise; or bariatric surgery. Complications, including seroma, wound dehiscence, skin necrosis, infection, hematoma and venous thromboembolism, were included if they required intervention. An adjusted logistic model was used to examine the effect of weight loss method on aggregate complication rates. RESULTS: A total of 307 patients were included: 77 (25%) lost weight through diet and exercise; and 230 (75%) through bariatric surgery. Results from the logistic model showed no difference in complication rates between weight loss methods (OR 1.01 [95% CI 0.51 to 2.02]). However, there was a strong correlation between body mass index at the time of surgery and complication rates (OR 1.05 [95% CI 1.02 to 1.08]; P<0.01). CONCLUSIONS: The findings reveal no difference in complication rates following abdominal body contouring procedures attributable to method of weight loss. Rather, there was a proportional rise in complication rates in patients with a higher body mass index at the time of surgery. Surgeons and patients should be aware of this trend, and it should be part of any discussion of abdominal body contouring procedures and informing patients of their risk profile.

HISTORIQUE: Les interventions de remodelage du corps après une perte de poids massive sont de plus en plus courantes. Malheureusement, elles continuent d'être associées à un taux de complication élevé. OBJECTIF: Évaluer l'influence de la méthode de perte de poids sur les complications après des interventions de remodelage de l'abdomen. MÉTHODOLOGIE: Les chercheurs ont fait l'évaluation rétrospective de patients qui avaient subi des interventions de remodelage sur une période de 11 ans et les ont stratifiés en deux groupes, selon la méthode de perte de poids: régime et exercice ou chirurgie bariatrique. Ils ont inclus les complications qui avaient nécessité une intervention, y compris le sérome, la déhiscence de la plaie, la nécrose cutanée, l'infection, l'hématome et la thromboembolie veineuse. Ils ont utilisé un modèle logistique rajusté pour examiner l'effet de la méthode de perte de poids sur les taux de complication globaux. RÉSULTATS: Au total, 307 patients ont été inclus dans l'étude, dont 77 (25 %) ont perdu du poids par suite d'un régime et d'exercice et 230 (75 %) après une chirurgie bariatrique. Les résultats du modèle logistique n'ont révélé aucune différence dans les taux de complications selon la méthode de perte de poids (RC 1,01 [95 % IC 0,51 à 2,02]). Cependant, ils ont constaté une forte corrélation entre l'indice de masse corporelle au moment de l'opération et les taux de complications (RC 1,05 [95 % IC 1,02 à 1,08]; P<0,01). CONCLUSIONS: Les résultats n'ont révélé aucune différence dans les taux de complication attribuables à la méthode de perte de poids après des interventions de remodelage abdominal. Ils ont plutôt démontré une augmentation proportionnelle des taux de complication chez les patients dont l'indice de masse corporelle était plus élevé lors de l'opération. Les chirurgiens et les patients devraient connaître cette tendance, qu'il faudrait intégrer aux discussions sur les interventions de remodelage abdominal et à l'information aux patients sur leur profil de risque.