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Introduction: Treatment of pregnancy‐associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons. Material and methods: We conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people. Results: The search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%). Conclusions: The exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research‐related risks. [ABSTRACT FROM AUTHOR]

This study (ISRCTN17174559) aimed to explore the efficacy and safety of a kind of herbal porridge (Hou Gu Mi Xi) on the clinical symptoms of functional dyspepsia (FD). This was a single‐center, single‐dose, prospective, double‐blind, randomized controlled trial involving 64 participants with FD (35 cases and 29 controls) for 2 months of intervention and 1 month of follow‐up. The 7‐point Global Overall Symptom Scale (GOSS), 36‐Item Short Form Survey (SF‐36), and other indicators were assessed at baseline (day 0), at days 15, 30, and 60 of treatment, and at follow‐up 1 month after the end of the intervention. Many participants with FD achieved remission of their epigastric symptoms at follow‐up on the 90th day after treatment with herbal porridge compared to the placebo group (45.71% vs. 20.69%, p =.036). Furthermore, herbal porridge appeared to be effective in improving the quality of life of participants with FD, which was reflected in the rising SF‐36 scores for physical role, bodily pain, emotional role, and mental health. Although adverse events were reported, there was no overall difference in the number of adverse events between the two groups (p =.578). Herbal porridge is another effective and safe method for improving the symptoms and quality of life in patients with FD. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11‐dhTxB2 testing has an impact on clinical outcomes. Methods: A multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11‐dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11‐dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90‐day follow‐up period. Results: A total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss‐of‐function allele (*2, *3) and 8.71% tested positive for urinary 11‐dhTxB2‐ indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P =.842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P =.012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P =.025). Conclusions: Personalized antiplatelet therapy based on the CYP2C19 genotype and 11‐dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11‐dhTxB2 testing in the provision of precise clinical treatment. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) loading ketoconazole (KCZ) have shown better efficacy on rats with tinea pedis than the marketed Daktarin® but clinical studies are still lacking. In this study, we described the clinical translation of ILs containing KCZ (KCZ‐ILs) from the lab into the clinic and evaluated the efficacy and safety of KCZ‐ILs in patients with tinea pedis. Thirty‐six enrolled participants were randomized to receive either KCZ‐ILs (KCZ, 4.72 mg/g) or Daktarin® (control group; KCZ, 20 mg/g) topically twice daily, making the lesion be covered with a thin layer of medication. The randomized controlled trial lasted for 8 weeks including 4 weeks of intervention and 4 weeks of follow‐up. Primary efficacy outcome was the proportion of treatment success responders, defined as patients achieving negative mycological result and ≥60% relative reduction in total clinical symptom score (TSS) from baseline at week 4. Secondary outcomes mainly for evaluating the relapse of disease included the proportion of treatment success individuals at week 8 and fungal recurrence rate at weeks 2, 3, 4, and 8. After 4 weeks of medication, 47.06% of the KCZ‐ILs subjects were treatment successes compared with only 25.00% of those using Daktarin®. Throughout the trial period, KCZ‐ILs induced a significantly lower recurrence rate (52.94%) than that of control patients (68.75%). Furthermore, KCZ‐ILs were found to be safe and well‐tolerated. In conclusion, ILs loading only 1/4 KCZ dose of Daktarin® showed a better efficacy and safety profile in the management of tinea pedis, creating a new opportunity for the treatment of skin diseases caused by fungal infection and is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Objective: Platelet‐rich plasma（PRP), with different concentration of leukocytes, may lead to varying effects in the treatment of cartilage lesions. So far, current research has not shown enough evidence on this. To evaluate the clinical efficacy and safety of intra‐articular injection with pure platelet‐rich plasma (P‐PRP) versus those of leukocyte platelet‐rich plasma (L‐PRP) in treating knee cartilage lesions, we conducted a double‐blind, randomized controlled clinical trial with a larger sample and longer follow‐up period. Methods: From October 2019 to October 2020, 95 patients were invited to participate in our study, and 60 (63.2%) were randomized to P‐PRP (n = 30) or L‐PRP (n = 30) groups. Patients from the two groups were treated with knee intra‐articular injections of P‐PRP or L‐PRP. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were assessed using an unpaired t‐test for independent samples preoperatively and at 6 weeks, 12 weeks, 6 months, and 12 months after intervention. Results: We followed up 27 cases in the P‐PRP group and 26 cases in the L‐PRP group. No significant differences in VAS and WOMAC scores were found between the two groups before the intervention (p > 0.05). The WOMAC Pain and VAS‐Motions scores of the P‐PRP group were significantly lower than those of the L‐PRP group at 6 weeks after the intervention (p < 0.05). While the long‐term clinical efficacy of both injections was similar and weakened after 12 months, more adverse events were found in the L‐PRP group. Conclusions: The short‐term results demonstrate a positive effect in reducing pain and improving function in patients with knee cartilage lesions in the two groups. While the P‐PRP injection showed better clinical efficacy in the early phase of postoperative rehabilitation and resulted in fewer adverse events, long‐term follow‐up showed similar and weakened efficacy after 12 months. Trial Registration: ChiCTR1900026365. Registered on October 3, 2019, http://www.chictr.org.cn/showproj.aspx?proj=43911. [ABSTRACT FROM AUTHOR]

Objective: To introduce a novel analytical approach for randomized controlled trials that are underpowered because of low participant enrollment or engagement.Data Sources: Reanalysis of data for 805 patients randomized as part of a pilot complex care intervention in 2015-2016 in a large delivery system. In the pilot randomized trial, only 64.6% of patients assigned to the intervention group participated.Study Design: A case study and simulation. The "Distillation Method" capitalizes on the frequently observed correlation between the probability of subjects' participation or engagement in the intervention and the magnitude of benefit they experience. The novel method involves three stages: first, it uses baseline covariates to generate predicted probabilities of participation. Next, these are used to produce nested subsamples of the randomized intervention and control groups that are more concentrated with subjects who were likely to participate/engage. Finally, for the outcomes of interest, standard statistical methods are used to re-evaluate intervention effectiveness in these concentrated subsets.Data Extraction Methods: We assembled secondary data on patients who were randomized to the pilot intervention for one year prior to randomization and two follow-up years. Data included program enrollment status, membership data, demographics, utilization, costs, and clinical data.Principal Findings: Using baseline covariates only, Generalized Boosted Regression Models predicting program enrollment performed well (AUC 0.884). We then distilled the full randomized sample to increasing levels of concentration and reanalyzed program outcomes. We found statistically significant differences in outpatient utilization and emergency department utilization (both follow-up years), and in total costs (follow-up year two only) at select levels of population concentration.Conclusions: By offering an internally valid analytic framework, the Distillation Method can increase the power to detect effects by redefining the estimand to subpopulations with higher enrollment probabilities and stronger average treatment effects while maintaining the original randomization. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of topical nepafenac 0.1% versus intravitreal triamcinolone acetonide (IVTA) at the conclusion of vitrectomy surgery versus no adjuvant therapy (NAT) in improving macular morphology post‐operatively in patients undergoing vitrectomy for epiretinal membrane (ERM), as measured by optical coherence tomography (OCT) imaging and best‐corrected visual acuity (BCVA). Methods: Design: Prospective randomized clinical trial Setting: Multi‐centre 80 patients scheduled to undergo vitrectomy surgery for idiopathic ERM were randomized to receive either IVTA (4 mg/0.1 cc) at the end of surgery, topical nepafenac sodium 0.1% TID for 1 month post‐operation or no adjuvant treatment (NAT). Optical coherence tomography (OCT) imaging, best‐corrected visual acuity and intraocular pressure (IOP) were measured before surgery, and 1 and 2 months post‐operation. Results: Although all three groups showed reduction in macular thickness post‐operation, the NAT group showed the most improvement, with a reduction of 136.18 ± 29.84 μm at two months. There was no statistically significant difference in macular thickness between the groups at each time point, p = 0.158. The NAT group also had the best recovery in BCVA with an improvement of 0.207 logMAR (10.35 letters) at two months post‐operation. There was no statistically significant difference in BCVA between the groups, p = 0.606. There was statistically significant difference in the IOP between the three groups, p = 0.04 only at 1‐month visit. The IVTA group had the highest rise in average IOP at both 1 and 2 months post‐operation (2.72 and 1.58 mmHg, respectively). Conclusion: Our study data suggest there was no advantage in the use of topical nepafenac or IVTA for post‐vitrectomy ERM surgery. [ABSTRACT FROM AUTHOR]

Purpose: To compare quality of vision and vision‐related quality of life (QOL) in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) or ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: Fifty‐four eyes of 54 patients with Fuchs' dystrophy from six corneal clinics in the Netherlands were randomized to DMEK or ultrathin DSAEK and examined preoperatively, and 3, 6 and 12 months postoperatively. Main outcome measures were corneal higher‐order aberrations (HOAs), contrast sensitivity, straylight and vision‐related QOL. Results: Posterior corneal HOAs decreased after DMEK and increased after ultrathin DSAEK (p ≤ 0.001) 3 months after surgery and correlated positively with best spectacle‐corrected visual acuity (12 months: r = 0.29, p = 0.04). Anterior and total corneal HOAs did not differ significantly between both techniques at any time point. Contrast sensitivity was better (p = 0.01), and straylight was lower (p = 0.01) 3 months after DMEK compared with ultrathin DSAEK; 95% confidence interval [CI] of log(cs) 1.10–1.35 versus 95% CI: 0.84 to 1.12, and 95% CI: log(s) 1.18 to 1.43 versus 95% CI: 1.41 to 1.66, respectively. Both were comparable at later time points. Vision‐related QOL (scale 0–100) did not differ significantly between both groups at any time point and improved significantly at 3 months (β = 12 [95% CI: 7 to 16]; p < 0.001), and subsequently between 3 and 12 months (β = 5 [95% CI: 0 to 9]; p = 0.06). Conclusions: Descemet membrane endothelial keratoplasty (DMEK) results in lower posterior corneal HOAs compared with ultrathin DSAEK. Contrast sensitivity and straylight recover faster after DMEK but reach similar levels with both techniques at 1 year. Vision‐related QOL improved significantly after surgery, but did not differ between both techniques. [ABSTRACT FROM AUTHOR]

Cancer‐related fatigue (CRF) is one of the most common chronic symptoms experienced by cancer patients. As moxibustion is a popular traditional therapy for managing fatigue, it can be an alternative strategy to treat CRF as well. Therefore, we rigorously designed a full‐scale, multicenter, assessor‐blinded, randomized controlled trial to evaluate the efficacy and safety of moxibustion treatment for CRF. Ninety‐six subjects suffering from CRF were recruited and randomly assigned to moxibustion group, sham moxibustion group, or usual care group. Both the moxibustion group and the sham group received moxibustion treatment for 8 weeks and the usual care group did not. Brief fatigue inventory (BFI) score and Functional Assessment of Cancer Therapy‐Fatigue score were used to assess CRF at baseline and weeks 5, 9, and 13. Questionnaires for the assessment of cognitive impairment, quality of life, and Cold–Heat and Deficiency–Excess patterns were also evaluated. BFI scores significantly decreased in moxibustion group compared to the usual care group (mean difference of −1.92, p < 0.001 at week 9 and mean difference of −2.36, p < 0.001 at week 13). Although the sham group also showed significant improvement during the treatment period, only the moxibustion group showed improvement after 4 weeks of follow‐up period (mean difference of −1.06, p < 0.001). There were no serious adverse events. Our findings confirmed the efficacy and safety of moxibustion for CRF compared to usual care. We also found that moxibustion has a prolonged treatment effect during 4 weeks of follow‐up period. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether closed suction drainage (CSD) is related to accelerated rehabilitation of patients after open reduction and internal fixation (ORIF) for closed distal femur fractures. Methods: This study was a prospective, randomized controlled clinical trial. Between October 2018 and June 2020, 160 closed distal femur fracture patients who were prepared for ORIF were prospectively randomized into two groups: a CSD group with the mean age of 57.91 ± 14.38 years (32 [40%] men and 48 [60%] women) and a non‐CSD group with the mean age of 59.73 ± 17.55 years (27 [34%] men and 54 [66%] women). Wound visual analogue scale (VAS) pain scores, peri‐wound skin temperature, hematocrit (Hct), hemoglobin (Hb) concentrations, hidden blood loss (HBL), dressing change, period of wound oozing, postoperative blood transfusion, and length of postoperative hospital stay were recorded. Postoperative wound complications, namely wound infections, wound haematoma, wound dehiscence, erythema of wound, and lower limb deep vein thrombosis (DVT) were collected. All the patients were administrated by a single surgical team and followed up for 1 month after the ORIF. Results: The patients without CSD were identified with lower peri‐wound skin temperature and wound VAS pain scores during the first three postoperative days (36.69 ± 0.33 vs 36.86 ± 0.38 °C, P = 0.002; 1.88 ± 0.82 vs 3.15 ± 1.15, P = 0.000). However, both the peri‐wound skin temperature and wound VAS pain scores did not differ significantly between the two groups on the fifth postoperative day. In addition, patients with CSD had a longer length of postoperative hospitalization time (11.45 ± 5.95 vs 9.78 ± 4.64 days, P = 0.049). There was no statistically significant difference between CSD and non‐CSD groups within 1 month after the ORIF regarding blood loss, period of wound oozing, and postoperative complications, such as incidence of wound infection, haematoma, erythema, dehiscence, and lower limb DVT. Conclusion: Prophylactic CSD after primary ORIF for closed distal femur fractures not only had no significant advantage to minimize blood loss and wound complications, but increased local inflammation and postoperative hospital stay, and thus we suggest that prophylactic CSD after primary ORIF for closed distal femur fractures is not recommended for optimized clinical pathways and accelerated recovery. [ABSTRACT FROM AUTHOR]

Introduction: Ear acupuncture carried out in primary care by trained midwives, with no specialist training in acupuncture, may be effective in alleviating pregnancy-related lower back and/or posterior pelvic girdle pain (LBPGP). The objective of this study was to assess the effect of ear acupuncture associated with standard obstetric care, in the primary-care setting, on LBPGP experienced by pregnant women.Material and Methods: This four-group, multicenter, randomized controlled trial was conducted at 18 public primary care centers in three regions in Spain, with the participation of 220 pregnant women at 24-36 weeks of gestation, aged 18 years or more, diagnosed with pregnancy-related LBPGP and who had not previously received ear acupuncture. The trial was conducted from March 2014 to December 2016. Participants were randomly assigned (1:1:1:1) to receive standard obstetric care plus two sessions (over 2 weeks) of verum ear acupuncture, or nonspecific ear acupuncture, or placebo ear acupuncture, or standard obstetric care alone. The primary outcome was change in pain intensity, assessed using a visual analog scale (0-100 mm) from baseline to the end of treatment (T2). Secondary outcomes included change or presence of pain at 3 months (T3) and at 1 year (T4) postpartum, and changes in responses to the Roland-Morris disability questionnaire (RMDQ) and Short Form-12 Health Survey (SF-12) at the end of treatment.Results: A total of 55 women were randomized to each group, and 205 completed the study. With respect to baseline values, the reduction in pain intensity among the verum ear acupuncture group vs standard obstetric care was significantly greater, both at T2 (65.8%, 95%CI 56.2-75.3 vs 25.1%, 95%CI 15.3-34.9) and at T3 (93.8%, 95%CI 88.7-99.0 vs 67.9%, 95%CI 55.3-80.5). Moreover, significant changes were found in the verum ear acupuncture group vs standard obstetric care at T2, in reduced RMDQ scores (70.9%, 95%CI 61.8-80.1 vs 21.2%, 95%CI 8.6-33.7) and in increased SF-12 scores on the physical scale (40.5%, 95%CI 31.5-49.4 vs 8.1%, 95%CI 0.8-15.5).Conclusions: After 2 weeks of treatment, ear acupuncture applied by midwives and associated with standard obstetric care significantly reduces lumbar and pelvic pain in pregnant women, improves quality of life and reduces functional disability. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the neuroprotective effect of Copolymer‐1 (Cop‐1) in patients with acute primary angle closure (APAC) in a randomized double‐masked controlled trial. Methods: After initial medical management, APAC patients were randomized to receive either subcutaneous Cop‐1 or placebo within 24 hr and at 1 week. After laser peripheral iridotomy (LPI), subjects underwent serial visual field (VF) tests and retinal nerve fibre layer (RNFL) thickness measurements with spectral‐domain optical coherence tomography. The primary outcome measure was mean number of progressing points (significant slope of ≥ 1 dB per year sensitivity loss) over 16 weeks based on pointwise linear regression analysis, and the secondary outcome measure was the change in RNFL thickness. Results: Thirty‐eight patients (19 in each group) completed the study. Twenty‐five (65.8%) were female, the majority being Chinese (86.8%) with mean age 62.5 years (SD 8.1). Patients in the Cop‐1 group were found to have mean of 0.32 (SD 0.95) progressing points compared to 2.74 (SD 5.31) in the placebo group (p = 0.09), while 3/19 (15.8%) of Cop‐1 treated patients had 1 or more progressing points compared to 7/19 (36.8%) in the placebo group (p = 0.14). There was no difference in change of RNFL thickness between groups (p = 0.57). We found improvement of mean deviation (MD) at week 16 in the Cop‐1 group (p = 0.01) compared to worsening of MD in the placebo group (p = 0.04). Conclusion: After APAC, there was no difference in VF progression (or RNFL thickness change) between Cop‐1 and placebo groups. However, there was improvement of MD in Cop‐1 treated patients. [ABSTRACT FROM AUTHOR]

Objective: Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy.Methods: This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (β-hCG) level of < 1500 IU/L. Women were assigned randomly to a single systemic injection of either 50 mg/m2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum β-hCG to < 20 IU/L or a negative urine pregnancy test without the need for any additional medical intervention. An intention-to-treat analysis was followed.Results: We recruited a total of 80 women, 42 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of β-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of β-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in β-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum β-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the subgroup of women with higher β-hCG. In women with successful conservative treatment, there was no significant difference in median β-hCG resolution times between study arms (17.5 (interquartile range (IQR), 14-28.0) days (n = 30) in the methotrexate group vs 14 (IQR, 7-29.5) days (n = 25) in the placebo group; P = 0.73).Conclusions: The results of our study do not support the routine use of methotrexate for the treatment of clinically stable women diagnosed with tubal ectopic pregnancy presenting with low serum β-hCG (< 1500 IU/L). Further work is required to identify a subgroup of women with tubal ectopic pregnancy and β-hCG ≥ 1500 IU/L in whom methotrexate may offer a safe and cost-effective alternative to surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Comparación entre una sola dosis de metotrexate sistémico y la conducta expectante en el tratamiento de casos de embarazo ectópico tubárico: un ensayo aleatorio controlado con placebo RESUMEN OBJETIVO: El metotrexate se utiliza de modo rutinario en todo el mundo para el tratamiento de las mujeres clínicamente estables con un embarazo ectópico tubárico. Esto sucede a pesar de la falta de evidencia rigurosa que demuestre que su eficacia es superior a la conducta expectante. El objetivo de este ensayo controlado aleatorio multicéntrico fue comparar las tasas de éxito del metotrexate con las de un placebo para el tratamiento cauteloso del embarazo ectópico tubárico. MÉTODOS: Este estudio se llevó a cabo en dos clínicas de control de gestación temprana en el Reino Unido entre agosto de 2005 y junio de 2014. Los criterios de inclusión fueron mujeres clínicamente estables con un diagnóstico ecográfico concluyente de embarazo ectópico tubárico, las cuáles presentaban una concentración sérica baja de la β hormona coriónica gonadotrópica (β-hCG) inferior a 1500 UI/L. Las mujeres fueron asignadas aleatoriamente a una sola inyección sistémica de 50 mg/m2 de metotrexate o a placebo. El resultado primario fue un indicador binario del éxito del tratamiento conservador, definido como la resolución de los síntomas clínicos y la disminución en el suero de la β-hCG a <20 UI/L o una prueba de embarazo negativa en orina sin la necesidad de ninguna intervención médica adicional. Se hizo un análisis por intención de tratar.Resultados: Se reclutó un total de 80 mujeres; a 42 de ellas se les asignó el metotrexate y a 38 el placebo. Los grupos del estudio se realizaron en función de la edad, el origen étnico, los antecedentes obstétricos, las características del embarazo y los niveles séricos de la β-hCG y la progesterona. Las tasas de éxito fueron similares para los dos grupos de estudio: 83% con metotrexate y 76% con placebo. En el análisis univariante, esta diferencia no fue estadísticamente significativa (χ2 (1 grado de libertad) = 0,53; P = 0,47). En la regresión logística multivariante, el nivel sérico de la β-hCG fue la única covariable que se encontró significativamente asociada con el resultado. Las probabilidades de fracaso aumentaron en un 0,15% por cada unidad de aumento de la β-hCG (cociente de probabilidad 1,0015 (IC 95%, 1,0002-1,003); P = 0,02). La tasa de éxito en las 14 mujeres con un nivel sérico de la β-hCG de 1000-1500 UI/L fue del 33% en las tratadas con conducta expectante frente al 62% en las que recibieron metotrexate. Esta diferencia no fue estadísticamente significativa, por lo que se necesitaría un tamaño de muestra mayor, lo suficiente como para poder detectar diferencias en el subgrupo de mujeres con una β-hCG más elevada. En las mujeres en las que el tratamiento conservador tuvo éxito, no hubo una diferencia significativa en la mediana de los tiempos de resolución de la ß-hCG entre los grupos del estudio (17,5 (amplitud intercuartílica (IQR), 14-28,0) días (n = 30) en el grupo de metotrexate frente a 14 (IQR, 7-29.5) días (n = 25) en el grupo de placebo; P = 0,73).Conclusiones: Los resultados de este estudio no apoyan el uso rutinario de metotrexate para el tratamiento de las mujeres clínicamente estables diagnosticadas con un embarazo ectópico tubárico que presenta un nivel sérico bajo la β-hCG (<1500 UI/L). Serán necesarios estudios adicionales para identificar un subgrupo de mujeres con embarazo ectópico tubárico y β-hCG ≥1500 UI/L para quienes el metotrexate puede ofrecer una alternativa segura y rentable en comparación con la cirugía. : : ,,。。 : 2005820146,2。,,β(beta human chorionic gonadotropin,β-hCG)<1500 IU/L。,(50 mg/m2 )。,β-hCG<20 IU/L,。。 : 80,42,38。2、、、β-hCG。2:83%,76%。,[χ2 (1)=0.53;P=0.47]。logistic,β-hCG。β-hCG,0.15%[,1.0015(95% CI,1.0002~1.003);P=0.02]。14β-hCG1000~1500 IU/L,33%,62%。,β-hCG。,2β-hCG(P=0.73),17.5[(interquartile range,IQR),14~28.0](n=30),14 (IQR,7~29.5)(n=25)。 : 、、β-hCG(<1500 IU/L)。,β-hCG>1500 IU/L、。. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to train doctors in collaborative and ethical communication regarding informed consent and assess the impact of training on the behaviour, stress and satisfaction of a physician. It shows that doctors strongly supported the training and did not demonstrate reduced stress and burnout. Results suggest the potential of training to improve a number of aspects of obtaining informed consent.

Aims Central sleep apnoea/Cheyne–Stokes respiration (CSA/CSR) is a risk factor for increased mortality and morbidity in heart failure (HF). Adaptive servo-ventilation (ASV) is a non-invasive ventilation modality for the treatment of CSA/CSR in patients with HF. Methods SERVE-HF is a multinational, multicentre, randomized, parallel trial designed to assess the effects of addition of ASV (PaceWave™, AutoSet CS™; ResMed) to optimal medical management compared with medical management alone (control group) in patients with symptomatic chronic HF, LVEF ≤45%, and predominant CSA. The trial is based on an event-driven group sequential design, and the final analysis will be performed when 651 events have been observed or the study is terminated at one of the two interim analyses. The aim is to randomize ∼1200 patients to be followed for a minimum of 2 years. Patients are to stay in the trial up to study termination. The first patient was randomized in February 2008 and the study is expected to end mid 2015. The primary combined endpoint is the time to first event of all-cause death, unplanned hospitalization (or unplanned prolongation of a planned hospitalization) for worsening (chronic) HF, cardiac transplantation, resuscitation of sudden cardiac arrest, or appropriate life-saving shock for ventricular fibrillation or fast ventricular tachycardia in implantable cardioverter defibrillator patients. Perspectives The SERVE-HF study is a randomized study that will provide important data on the effect of treatment with ASV on morbidity and mortality, as well as the cost-effectiveness of this therapy, in patients with chronic HF and predominantly CSA/CSR. Trial registration ISRCTN19572887 [ABSTRACT FROM AUTHOR]

Aims The effect on mortality and morbidity of pharmacist-led intervention to optimize pharmacological therapy in patients with systolic heart failure (HF) has not been tested in a large-scale, long-term, clinical trial. Methods We describe the rationale and design of a UK, primary care-based, prospective cluster-randomized controlled trial of a pharmacist-led intervention in HF and report baseline characteristics of the patients randomized. Eighty-seven practices (1092 patients) were assigned to the intervention arm and 87 practices (1077 patients) to usual care. The average age of patients at baseline was 71 years, 70% were male, 86% were treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and 62% with a beta-blocker. Data for the primary outcome of death from any cause or hospitalization for HF will be available up to 31 December 2010, giving a mean follow-up of 5 years. More than 750 patients would have experienced the primary outcome during this period. The first secondary outcome is death from any cause or hospitalization for a cardiovascular reason. Deaths and hospitalizations are being identified using the Scottish National Health Service electronic patient record-linkage system (hence the delay between the end of follow-up and database lock). Conclusion This trial is powered to provide a robust evaluation of the effect of pharmacist-led treatment optimization in patients with systolic HF in primary care. [ABSTRACT FROM AUTHOR]

In a 4-year follow-up of a randomized controlled trial, this study aimed to evaluate the longer-term effects of a peer-led infant feeding intervention that was delivered during the first year of life. The original intervention used monthly home visits from trained volunteers to improve infant feeding practices among a sample of low-income mothers in two disadvantaged London boroughs. Outcome measures at follow-up included children's eating and drinking habits, general and dental health, and BMI. Data were collected via structured face-to-face interviews and postal questionnaires. Of 212 women who completed the original trial, 101 took part in the follow-up (55 intervention, 46 control). Children's mean age at follow-up was 4 years 7 months. There is little evidence that the intervention had an important effect on children's current BMI, caries levels or consumption of fruit and vegetables. However, mothers from the intervention group had better nutritional knowledge and confidence. Intervention group children also consumed more pure fruit juice [relative risk (RR) = 1.57; 95% confidence interval (CI) 0.99, 2.49] and were more likely to never drink squash (RR = 1.76; 95% CI 1.20, 2.58). The data suggest that the original peer support intervention had a small number of positive long-term effects. [ABSTRACT FROM AUTHOR]

Objective To describe the design, methods and baseline findings of a multi-level prevention intervention to increase consistent condom use among persons at public social sites in Kingston, Jamaica, who have new or concurrent sexual partnerships. Methods A two-arm randomized controlled trial (RCT) of 147 sites where persons meet new sex partners. Sites were identified by community informants as places where people meet new sexual partners, which include bars, street locations, bus stops, malls and others. Sites were sorted into 50 clusters based on geographic proximity and type of site and randomized to receive a multi-level site-based intervention or not. Intervention components include on-site HIV testing, condom promotion and peer education. Effectiveness of the intervention will be measured by comparing the proportion of persons with new or multiple partners in the past year who report recent inconsistent condom use at intervention vs. control sites. Results Baseline surveys were conducted at 66 intervention (711 men, 845 women) and 65 control sites (654 men, 738 women). Characteristics of intervention and control sites as well as the characteristics of patrons at these sites were similar. The outcome variable was balanced with approximately 30% of men and 25% of women at intervention and control sites reporting a new partner or more than one partner in the past year and recent inconsistent condom use. Conclusions The baseline findings confirm that the population is an appropriate target group for HIV prevention and that randomization will provide the means to estimate programme effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: To assess the comparative effectiveness, efficacy, and tolerability of lamotrigine (LTG) and sustained-release carbamazepine (CBZ) in the treatment of newly diagnosed epilepsy in the elderly. Methods: Patients aged 65 years or older, who had experienced at least two unprovoked partial and/or generalized tonic–clonic seizures, were randomized to receive LTG (n = 93) or CBZ (n = 92) according to a multicenter double-blind, parallel-group design. Trial duration was 40 weeks and included a 4-week dose escalation followed by a maintenance phase during which dosages could be adjusted according to response. Initial, maintenance and maximum dosages were 25 mg, 100 mg, and 500 mg per day for LTG, and 100 mg, 400 mg, and 2,000 mg per day for CBZ, respectively. The primary end point was retention in the trial. Results: In the LTG group, 68 patients (73%) completed the 40-week study period compared with 61 (67%) in the CBZ group, a nonsignificant difference. Time to withdrawal from any cause did not differ between groups (p = 0.34). The number of subjects who completed the 40-week period and were seizure free in the last 20 weeks was 48 (52%) in the LTG group and 52 (57%) in the CBZ group. Adverse events leading to withdrawal occurred in 13 (14%) subjects in the LTG group and 23 (25%) subjects in the CBZ group. Conclusion: LTG and CBZ showed comparable effectiveness, with a trend for higher seizure-free rates for CBZ and better tolerability for LTG. Differences in outcome compared with previous trials may be related to different dosing rates and use of a sustained-release formulation for CBZ. [ABSTRACT FROM AUTHOR]

The Ginkgo biloba special extract EGb 761 seems to produce neuroprotective effects in neurodegenerative diseases of multifactorial origin. There is still debate about the efficacy of Ginkgo biloba special extract EGb 761 compared with second-generation cholinesterase inhibitors in the treatment of mild to moderate Alzheimer's dementia. Our aim is to assess the efficacy of the Ginkgo biloba special extract E.S. in patients with dementia of the Alzheimer type in slowing down the disease's degenerative progression and the patients' cognitive impairment compared with donepezil and placebo. The trial was designed as a 24-week randomized, placebo-controlled, double-blind study. Patients aged 50–80 years, suffering from mild to moderate dementia, were allocated into one of the three treatments: Ginkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. The degree of severity of dementia was assessed by the Syndrom Kurz test and the Mini-Mental State Examination. Clinical Global Impression score was recorded to assess the change in the patients’ conditions and the therapeutic efficacy of tested medications. Our results confirm the clinical efficacy of Ginkgo biloba E.S. (Flavogin) in the dementia of the Alzheimer type, comparable with donepezil clinical efficacy. There are few published trials that have directly compared a cholinesterase inhibitor with Ginkgo for dementia. This study directly compares a cholinesterase inhibitor with Ginkgo biloba for dementia of the Alzheimer type and could be a valid contribution in this debate. Our study suggests that there is no evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimer's dementia, so the use of both substances can be justified. In addition, this study contributes to establish the efficacy and tolerability of the Ginkgo biloba special extract E.S. in the dementia of the Alzheimer type with special respect to moderately severe stages. [ABSTRACT FROM AUTHOR]

The randomized controlled trial has been used in medical research for a little over half a century. This manuscript provides an overview of some of the history and evolution of the randomized controlled trial during this period. There exists hierarchies of evidence for therapeutic, diagnostic and prognostic questions, and the randomized controlled trial is at the top of the therapeutic hierarchy. Despite being at the top of the therapeutic hierarchy randomization in itself does not guarantee the trial results approximate the true effect. Issues that result in systematic and nonsystematic deviations from the truth in randomized controlled trials must also be considered. We present a model for evidence-based decision making that includes the following components; the clinical state, patient preferences, research evidence from a range of studies and clinical expertise. We discuss the role of the randomized controlled trial within evidence based decision making. [ABSTRACT FROM AUTHOR]

Abstract. Devereaux PJ, Yusuf S (McMaster University, Hamilton, Ontario, Canada). The evolution of the randomized controlled trial and its role in evidence-based decision making (Clinical Trials). J Intern Med 2003; 254: 105–113. The randomized controlled trial has been used in medical research for a little over half a century. This manuscript provides an overview of some of the history and evolution of the randomized controlled trial during this period. There exists hierarchies of evidence for therapeutic, diagnostic and prognostic questions, and the randomized controlled trial is at the top of the therapeutic hierarchy. Despite being at the top of the therapeutic hierarchy randomization in itself does not guarantee the trial results approximate the true effect. Issues that result in systematic and nonsystematic deviations from the truth in randomized controlled trials must also be considered. We present a model for evidence-based decision making that includes the following components: the clinical state, patient preferences, research evidence from a range of studies and clinical expertise. We discuss the role of the randomized controlled trial within evidence-based decision making. [ABSTRACT FROM AUTHOR]