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Background: Therapy decision-making (TDM) is an essential medical skill. However, teaching therapeutic reasoning poses significant challenges. We present a comprehensive TDM course for medical students and report on student satisfaction with the educational strategies, their perceived importance of various TDM domains, and their self-efficacy in incorporating these elements into clinical decisions., Methods: Three student cohorts participated in a 16-week TDM course, which included self-instruction modules, application assignments, faculty symposia, and application seminars as educational strategies. The course focused on TDM and emphasized how factors such as the patient's diagnosis, needs and preferences, treatment options, physicians' viewpoints, the patient-physician relationship, and contexts of medical practice impact TDM. After the course, students completed a before-and-after survey assessing their satisfaction with the educational strategies, their perceived importance of ten TDM domains, and their ability to incorporate these domains into patient management. Scores ranged from 1 to 10. Students from the first two cohorts completed a 1- and 2-year follow-ups., Results: A total of 387 students completed the course. All educational strategies were well-received, with self-instruction modules and faculty symposia yielding the highest satisfaction rates (94.8% and 88.6% respectively). Before-and-after evaluations indicated that students` perceived importance of the TDM domains increased from an average of 8.0 ± 2.4 at baseline to 9.9 ± 1.0 after the course. Additionally, their perceived ability to integrate TDM domains into practice rose from an average of 5.2 ± 3.2 to 9.4 ± 1.5 by the end of the course. Follow-up results showed a decrease in these outcomes over time., Conclusion: This course serves as a successful model for systematically teaching TDM to medical students., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided consent to participate in the evaluation of the showcased medical education innovation. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study aims to assess the effectiveness of training medical students to perform two clinical procedures using unsupervised simulation with remote asynchronous feedback, compared to an intensive workshop with in-person feedback., Design, Setting, and Participants: Third-year medical students were recruited and randomized into 2 groups: Thoracentesis or paracentesis. Within each group, participants were further randomized into either unsupervised simulation with remote asynchronous feedback (experimental group; EG) or a 2-hour workshop (control group; CG). The EG underwent two unsupervised 20-minute training sessions and received remote asynchronous feedback. The CG had a 2-hour workshop where they received in-person feedback. After training, students were assessed using the objective structured assessment of technical skills (OSATS) scale. Twenty students in thoracentesis and 23 in paracentesis training completed the 2 training sessions with remote and asynchronous feedback, and 30 students for both thoracentesis and paracentesis groups completed the 2-hour workshop., Results: The EG achieved a significantly higher passing rate than the CG on both procedures (thoracentesis 80% vs. 43%, paracentesis 91% vs. 67%, p-value< 0.05)., Conclusion: The asynchronous educational method allowed EG students to achieve higher performance than CG students. This novel modality allowed students and instructors to train and assess at their own pace., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the impact of potential risk of bias elements on effect estimates in randomized trials., Study Design and Setting: We conducted a systematic survey of meta-epidemiological studies examining the influence of potential risk of bias elements on effect estimates in randomized trials. We included only meta-epidemiological studies that either preserved the clustering of trials within meta-analyses (compared effect estimates between trials with and without the potential risk of bias element within each meta-analysis, then combined across meta-analyses; between-trial comparisons), or preserved the clustering of substudies within trials (compared effect estimates between substudies with and without the element, then combined across trials; within-trial comparisons). Separately for studies based on between- and within-trial comparisons, we extracted ratios of odds ratios (RORs) from each study and combined them using a random-effects model. We made overall inferences and assessed certainty of evidence based on Grading of Recommendations, Assessment, development, and Evaluation and Instrument to assess the Credibility of Effect Modification Analyses., Results: Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty). The impact of patients or outcome assessors blinding on other outcomes, and the impact of blinding of health-care providers, data collectors, or data analysts, remain uncertain. Trials stopped early for benefit probably overestimate effects (moderate certainty). Trials with imbalanced cointerventions may overestimate effects, while trials with missing outcome data may underestimate effects (low certainty). Influence of baseline imbalance, compliance, selective reporting, and intention-to-treat analysis remain uncertain., Conclusion: Failure to ensure random sequence generation or adequate allocation concealment probably results in modest overestimates of effects. Lack of patients blinding probably leads to substantial overestimates of effects for patient-reported outcomes. Lack of blinding of outcome assessors results in substantial effect overestimation for subjective outcomes. For other elements, though evidence for consistent systematic overestimate of effect remains limited, failure to implement these safeguards may still introduce important bias., Competing Interests: Declaration of competing interest SA, DB, PR, KFS, DZ, and GHG are coauthors of one or more meta-epidemiological studies that this systematic survey included. This work was supported by the Einstein Foundation Berlin as part of the Einstein Foundation Award for Promoting Quality in Research. The contents are those of the authors and do not necessarily represent the official views of, nor an endorsement by, the Einstein Foundation or the award jury. Authors do not have any personal financial interests or professional relationships related to the subject matter but not directly to this manuscript. There are no patents or copyrights licensed to the author(s) that are relevant to the work submitted for publication. No additional relationships or activities to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Context: Pain is common among cancer patients. The evidence recommends using strong opioids in moderate to severe cancer pain. No conclusive evidence supports the effectiveness of adding acetaminophen to patients with cancer pain who are already using this regime., Objectives: To assess the analgesic efficacy of acetaminophen in hospitalized cancer patients with moderate to severe pain receiving strong opioids., Methods: In this randomized blinded clinical trial, hospitalized cancer patients with moderate or severe acute pain managed with strong opioids were randomized to acetaminophen or placebo. The primary outcome was pain intensity difference between baseline and 48 hours using the Visual Numeric Rating Scales (VNRS). Secondary outcomes included change in morphine equivalent daily dose (MEDD), and patients' perception of improved pain control., Results: Among 112 randomized patients, 56 patients received placebo, 56 acetaminophen. Mean (standard deviation [SD]) decrease in pain intensity (VNRS) at 48 hours were 2.7 (2.5) and 2.3 (2.3), respectively (95% Confidence Interval (CI) [-0.49; 1.32]; P = 0.37). Mean (SD) change in MEDD was 13.9 (33.0) mg/day and 22.4 (57.7), respectively (95% CI [-9.24; 26.1]; P = 0.35). The proportion of patients perceiving pain control improvement after 48 hours was 82% in the placebo and 80% in the acetaminophen arms (P = 0.81)., Conclusion: Among patients with cancer pain on strong opioid regime, acetaminophen may not improve pain control, or decrease total opioid use. These results add to the current evidence available suggesting not to use acetaminophen as an adjuvant for advanced cancer patients with moderate to severe cancer pain who are on strong opioids., Competing Interests: DISCLOSURES AND ACKNOWLEDGMENTS This is an investigator-initiated trial funded by the Chilean National Grant for Research and Development in Health (Fondo Nacional de Innovación y Desarrollo en Salud - FONISSA18I0039). The PI and sponsor of this research project is Ofelia Leiva. This research project did not have financial support by the industry. The investigators maintain full autonomy in the design, conduct, analyses, and reporting of the study. The author declare that they do not have any conflict of interest. The authors retained full control of the primary data. This study was supported by various medical professionals, nursing, and residents. The authors are grateful to the patients and their families. On the other hand, this study was possible for funding from the Chilean National Grant for Research and Development in Health (Fondo Nacional de Innovación y Desarrollo en Salud – FONIS). All authors read, commented on, and approved the final manuscript., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias., Study Design and Setting: We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two reviewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above., Results: Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items., Conclusion: Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cancer pain is one of the most frequent and relevant symptoms in cancer patients and impacts on patient's quality of life. International and local standards recommend as an initial strategy the use of an analgesic scheme composed of strong opioids associated with adjuvants such as acetaminophen, based upon the assumption that combining drugs could have a better analgesic effect, could allow lowering opioid dosing, and could prevent the occurrence of adverse effects of opioids. However, there is uncertainty about the impact of acetaminophen as an adjuvant in patients who use strong opioids for moderate to severe pain management in cancer patients. The aim of this study is to assess the efficacy and safety of intravenous acetaminophen associated with strong opioids in hospitalized adult cancer patients who have moderate to severe cancer-related pain., Methods: We will perform a randomized double-blinded controlled study comparing intravenous acetaminophen 1 g 4 times a day versus placebo for 48 h as an adjuvant to strong opioids. We will assess pain intensity as a primary outcome, using the verbal numerical rating scale (VNRS, I0 to 10 scale with higher scores meaning higher pain intensity), and we will compare the mean difference in pain intensity between baseline and 48 h among the placebo and intervention groups. We estimate that a decrease of 1 point in the VNRS would be clinically significant. Assuming a standard deviation in pain intensity of 1.7 points, an alpha of 0.025, and a power of 0.8, we estimate a sample size of 112 patients, with 56 patients in each arm. Secondary outcomes include the difference in total opioid use between baseline and at 48 h among the groups, and adverse effects such as drowsiness, constipation, nausea, and vomiting would be evaluated., Discussion: The randomized, double-blind, placebo-controlled design is the best strategy to assess the efficacy of acetaminophen as an adjuvant in adult cancer patients with moderate to severe pain who are receiving strong opioids. We expect to contribute to national and international guidelines with these results., Trial Registration: Clinicaltrials.gov NCT04779567 . Registered on March 3, 2021. Retrospectively registered., (© 2022. The Author(s).)

Clinical rotations are an essential part of Internal Medicine (IM) residency programmes, where curricular objectives are carried out. To our knowledge, there are no validated instruments to assess IM clinical rotations. Our objective was to develop an instrument for residents to assess the quality of clinical rotations in an IM residency programme, and to test the psychometric properties of the instrument. A mixed methodology was used, including qualitative and quantitative phases. Items were proposed by a group of experts based on previously identified residency needs, followed by a quantitative phase to generate consensus among educators and residents to define which items would be included in the instrument (Delphi panel). After generating the instrument, psychometric tests were performed to assess construct validity (factor analysis) and reliability (Raykov's reliability coefficient). We obtained a 15-item instrument after two Delphi rounds: Internal Medicine Program Instrument 15-items ( IMPRINT-15 ). Sixty-two residents answered 428 surveys using a Likert scale during 7 months (response rate 98.9%). The median score was 4.3 (IQR 3.9-4.7) (scale from 1 to 5). The factor analysis showed two domains in the clinical rotation assessment: (1) teaching and care activities; (2) evaluation and feedback. The instrument is reliable with Raykov's reliability coefficient of 0.86. Also, Raykov's reliability coefficient for the domains were 0.89 and 0.83, respectively. The IMPRINT-15 instrument is a bi-dimensional, valid and reliable questionnaire to evaluate the perceived quality by residents of the IM clinical rotations. Also, it constitutes the first validated instrument in this field worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients undergoing haemodialysis (HD) through a central venous catheter (CVC) are exposed to several risks, being a catheter-related infection (CRI) and a CVC lumen thrombosis among the most serious. Standard of care regarding CVCs includes their sealing with heparin lock solutions to prevent catheter lumen thrombosis. Other lock solutions to prevent CRI, such as antimicrobial lock solutions, have proven useful with antibiotics solutions, but not as yet for non-antibiotic antimicrobial solutions. Furthermore, it is uncertain if these solutions have a negative effect on thrombosis incidence., Objectives: To assess the efficacy and safety of antimicrobial (antibiotic, non-antibiotic, or both) catheter lock solutions for preventing CRI in participants undergoing HD with a CVC., Search Methods: We searched the Cochrane Kidney and Transplant Specialised Register up to 18 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov., Selection Criteria: We included all randomised or quasi-randomised control trials (RCTs) comparing antimicrobial (antibiotic and non-antibiotic) lock solutions to standard lock solutions, in participants using a CVC for HD, without language restriction., Data Collection and Analysis: Two authors independently assessed studies for eligibility, and two additional authors assessed for risk of bias and extracted data. We expressed results as rate ratios (RR) per 1000 catheter-days or 1000 dialysis sessions with 95% confidence intervals (CI). Statistical analyses were performed using the random-effects model., Main Results: Thirty-nine studies, enrolling 4216 participants, were included in this review, however only 30 studies, involving 3392 participants, contained enough data to be meta-analysed. Risk of bias was low or unclear for most domains in the majority of the included studies.Studies compared antimicrobial lock solutions (antibiotic and non-antibiotic) to standard sealing solutions (usually heparin) of the CVC for HD. Fifteen studies used antibiotic lock solutions, 21 used non-antibiotic antimicrobial lock solutions, and 4 used both (antibiotic and non-antibiotic) lock solutions. Studies reported the incidence of CRI, catheter thrombosis, or both.Antimicrobial lock solutions probably reduces CRI per 1000 catheter-days (27 studies: RR 0.38, 95% CI 0.27 to 0.53; I 2 = 54%; low certainty evidence), however antimicrobial lock solutions probably makes little or no difference to the risk of thrombosis per 1000 catheter days (14 studies: RR 0.79, 95% CI 0.52 to 1.22; I 2 = 83%; very low certainty evidence). Subgroup analysis of antibiotic and the combination of both lock solutions showed that both probably reduced CRI per 1000 catheter-days (13 studies: RR 0.30, 95% CI: 0.22 to 0.42; I 2 = 47%) and risk of thrombosis per 1000 catheter-days (4 studies: RR 0.26, 95% CI: 0.14 to 0.49; I 2 = 0%), respectively. Non-antibiotic antimicrobial lock solutions probably reduced CRI per 1000 catheter-days for tunnelled CVC (9 studies: RR 0.60, 95% CI 0.40 to 0.91) but probably made little or no difference with non-tunnelled CVC (4 studies: RR 0.93, 95% CI 0.48 to 1.81). Subgroup analyses showed that antibiotic (5 studies: RR 0.76, 95% CI 0.42 to 1.38), non-antibiotic (8 studies: RR 0.85, 95% CI 0.44 to 1.66), and the combination of both lock solutions (3 studies: RR 0.63, 95% CI 0.22 to 1.81) made little or no difference to thrombosis per 1000 catheter-days compared to control lock solutions., Authors' Conclusions: Antibiotic antimicrobial and combined (antibiotic-non antibiotic) lock solutions decreased the incidence of CRI compared to control lock solutions, whereas non-antibiotic lock solutions reduce CRI only for tunnelled CVC. The effect on thrombosis incidence is uncertain for all antimicrobial lock solutions. Our confidence in the evidence is low and very low; therefore, better-designed studies are needed to confirm the efficacy and safety of antimicrobial lock solutions.

Background: Sudden cardiac death (SCD) is one of the main causes of cardiac death. There are two main strategies to prevent it: managing cardiovascular risk factors and reducing the risk of ventricular arrhythmias. Implantable cardiac defibrillators (ICDs) constitute the standard therapy for both primary and secondary prevention; however, they are not widely available in settings with limited resources. The antiarrhythmic amiodarone has been proposed as an alternative to ICD., Objectives: To evaluate the effectiveness of amiodarone for primary or secondary prevention in SCD compared with placebo or no intervention or any other antiarrhythmic drugs in participants at high risk (primary prevention) or who have recovered from a cardiac arrest or a syncope due to Ventricular Tachycardia/Ventricular Fibrillation, or VT/VF (secondary prevention)., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO) and LILACS on 26 March 2015. We reviewed reference lists of included studies and selected reviews on the topic, contacted authors of included studies, screened relevant meetings and searched in registers for ongoing trials. We applied no language restrictions., Selection Criteria: Randomised and quasi-randomised trials assessing the efficacy of amiodarone versus placebo, no intervention, or other antiarrhythmics in adults. For primary prevention we considered participants at high risk for SCD. For secondary prevention we considered participants recovered from cardiac arrest or syncope due to ventricular arrhythmias., Data Collection and Analysis: Two authors independently assessed the trials for inclusion and extracted relevant data. We contacted trial authors for missing data. We performed meta-analyses using a random-effects model. We calculated risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CIs). Three studies included more than one comparison., Main Results: We included 24 studies (9,997 participants). Seventeen studies evaluated amiodarone for primary prevention and six for secondary prevention. Only three studies used an ICD concomitantly with amiodarone for the comparison (all of them for secondary prevention).For primary prevention, amiodarone compared to placebo or no intervention (17 studies, 8383 participants) reduced SCD (RR 0.76; 95% CI 0.66 to 0.88), cardiac mortality (RR 0.86; 95% CI 0.77 to 0.96) and all-cause mortality (RR 0.88; 95% CI 0.78 to 1.00). The quality of the evidence was low.Compared to other antiarrhythmics (three studies, 540 participants), amiodarone reduced SCD (RR 0.44; 95% CI 0.19 to 1.00), cardiac mortality (RR 0.41; 95% CI 0.20 to 0.86) and all-cause mortality (RR 0.37; 95% CI 0.18 to 0.76). The quality of the evidence was moderate.For secondary prevention, amiodarone compared to placebo or no intervention (two studies, 440 participants) appeared to increase the risk of SCD (RR 4.32; 95% CI 0.87 to 21.49) and all-cause mortality (RR 3.05; 1.33 to 7.01). However, the quality of the evidence was very low. Compared to other antiarrhythmics (four studies, 839 participants) amiodarone appeared to increase the risk of SCD (RR 1.40; 95% CI 0.56 to 3.52; very low quality of evidence), but there was no effect in all-cause mortality (RR 1.03; 95% CI 0.75 to 1.42; low quality evidence).Amiodarone was associated with an increase in pulmonary and thyroid adverse events., Authors' Conclusions: There is low to moderate quality evidence that amiodarone reduces SCD, cardiac and all-cause mortality when compared to placebo or no intervention for primary prevention, and its effects are superior to other antiarrhythmics.It is uncertain if amiodarone reduces or increases SCD and mortality for secondary prevention because the quality of the evidence was very low.

Background: Feedback is one of the most important tools to improve teaching in medical education., Aim: To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties., Material and Methods: A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach’s alpha)., Results: Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947., Conclusions: MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.

Background: Treatment with proton pump inhibitors (PPIs) improves clinical outcomes in patients with peptic ulcer bleeding. However, the optimal dose and route of administration of PPIs remains controversial., Objectives: To evaluate the efficacy of different regimens of PPIs in the management of acute peptic ulcer bleeding using evidence from direct comparison randomized controlled trials (RCTs).We specifically intended to assess the differential effect of the dose and route of administration of PPI on mortality, rebleeding, surgical intervention, further endoscopic haemostatic treatment (EHT), length of hospital stay, transfusion requirements and adverse events., Search Methods: We searched CENTRAL (in The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (from inception to September 2010) and proceedings of major gastroenterology meetings (January 2000 to September 2010), without language restrictions. Original investigators were contacted to request missing data., Selection Criteria: RCTs that compared at least two different regimens of the same or a different PPI in patients with acute peptic ulcer bleeding, diagnosed endoscopically., Data Collection and Analysis: Two reviewers independently selected studies, extracted data and assessed risk of bias. We synthesized data using the Mantel-Haenszel random-effects method and performed multivariate meta-regression with random permutations based on Monte Carlo simulation. We measured heterogeneity with the I² statistic and Cochrane Q test and assessed publication bias with funnel plots and Egger's test. We graded the overall quality of evidence using the GRADE approach., Main Results: Twenty two RCTs were included; risk of bias was high in 17 and unclear in 5. The main analysis included 13 studies (1716 patients) comparing "high" dose regimens (72-hour cumulative dose > 600 mg of intravenous PPI) to other doses; there was no significant heterogeneity for any clinical outcome. We found low quality evidence that did not exclude a potential reduction or increase in mortality, rebleeding, surgical interventions or endoscopic haemostatic treatment (EHT) with "high" dose regimens. For mortality, pooled risk ratio (RR) was 0.85 (95% confidence interval (CI) 0.47 to 1.54); pooled risk difference (RD) was 0 more deaths per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more deaths per 100 treated). For rebleeding, pooled RR was 1.27 (95% CI 0.96 to 1.67); pooled RD was 2 more rebleeding events per 100 patients treated with "high" dose (95% CI from 0 fewer to 5 more rebleeding events per 100 treated). For surgical interventions, pooled RR was 1.33 (95% CI 0.63 to 2.77); pooled RD was 1 more surgical intervention per 100 patients treated with "high" dose (95% CI from 1 fewer to 2 more surgical interventions per 100 treated). For further EHT, pooled RR was 1.39 (95% CI 0.88 to 2.18), pooled RD was 2 more events per 100 patients treated with "high" dose PPI (95% CI from 1 fewer to 5 more events per 100 treated). We found moderate quality evidence suggesting no important difference between the two regimens with regards to length of hospital stay (mean difference (MD) 0.26 days; 95% CI -0.08 to 0.6 days) or blood transfusion requirements (MD 0.05 units; 95% CI -0.21 to 0.3 units). There was visual and statistical evidence of "inverse" publication bias for mortality (missing small studies with favourable outcomes for "high" dose), but not for any other outcome. The results were similar for all subgroup analyses (according to risk of bias, geographical location, route of administration for non-"high" dose regimens, continuous infusion vs. bolus administration for intravenous non-"high" regimens group), sensitivity analyses (restriction to patients who had EHT for high risk stigmata, use of different dose thresholds for comparative regimens) and post hoc analyses (inclusion of all studies (N = 22) that compared at least two PPI regimens with different cumulative 72 hour doses; restriction of the previous analysis to patients who had EHT for high risk stigmata). Meta-regression analysis did not show any statistically significant associations between treatment effect (for the outcomes of mortality, rebleeding and surgical intervention) and the three study-level factors that were assessed (geographical location (Asia versus not Asia), route of PPI administration (intravenous versus oral), within-study ratio among the 72-hour cumulative doses of the two PPI regimens)., Authors' Conclusions: There is insufficient evidence for concluding superiority, inferiority or equivalence of high dose PPI treatment over lower doses in peptic ulcer bleeding.

Background: Collapsing glomerulopathy is a cause of nephrotic syndrome with massive proteinuria secondary to podocyte proliferation and glomerular collapse. It is characterized by an almost inevitable progression to end stage renal failure, poor response to treatment and high post-transplant recurrence. Its frequency has increased in recent years due to its common association with Human Immunodeficiency Virus (HIV) infection and the growing recognition of new etiologic agents such as drugs and parvovirus B19. Therefore, it is a disease of growing interest for clinicians. The aim of this review is to update the clinical presentation, diagnosis, pathogenesis and therapeutic alternatives of this disease.

Background: Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain., Objectives: To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer., Search Strategy: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts., Selection Criteria: Randomized controlled trials (RCTs) comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer., Data Collection and Analysis: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies., Main Results: Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies had a significant benefit. Side-effects were inconsistently reported., Authors' Conclusions: Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.

Rationale, Aims and Objectives: To summarize 20-year experience of conducting a workshop designed for educators who wish to improve their teaching skills of evidence based medicine (EBM). The goal is to provide tips for educators interested in replicating this educational model., Methods: Qualitative description of factors associated with the success of the workshop., Results: The factors considered by instructors to be most helpful are: the small group interactive design, role-play and simulation of real world learning environments, a mentorship model and high educator to learner ratio., Conclusions: Although this experience is observational and does not represent high quality evidence, certain attributes in the design of EBM workshops may lead to better dissemination of EBM concepts. Educators may consider empirically applying some of these attributes and testing their efficacy in comparative studies.

Actinomycosis is a rare, chronic disease caused by a group of anaerobic Gram-positive bacteria that normally colonize the mouth, colon, and urogenital tract. Infection involving the cervicofacial area is the most common clinical presentation, followed by pelvic region and thoracic involvement. Due to its propensity to mimic many other diseases and its wide variety of symptoms, clinicians should be aware of its multiple presentations and its ability to be a 'great pretender'. We describe herein three cases of unusual presentation: an inferior caval vein syndrome, an acute cholecystitis, and an acute cardiac tamponade. We review the literature on its epidemiology, clinical presentation, diagnosis, treatment, and prognosis.

Background and Goals: Adenosine deaminase (ADA) levels are used for diagnosing tuberculosis in several locations and although many studies have evaluated ADA levels in ascitic fluid. These studies have defined arbitrary cut-off points creating difficulties in the clinical application of the results. The goals of this study are: to determine the usefulness of ADA levels in ascitic fluid as a diagnostic test for peritoneal tuberculosis (PTB) and define the best cut-off point., Study: A systematic review was done on the basis of 2 independent searches. We selected prospective studies that included consecutive patients. Diagnosis of PTB had to be confirmed by bacteriologic or histologic methods and ADA levels determined by the Giusti method. Inclusion/exclusion criteria were applied by 2 independent reviewers. A receiver operating characteristic curve was constructed to establish the optimal cut-off point and the likelihood ratios (LRs) estimated using fixed-effect pooled method., Results: Twelve prospective studies were found. Four of them met the inclusion criteria and were thus included in the meta-analysis. They included 264 patients, of which 50 (18.9%) had PTB. ADA levels showed high sensitivity (100%) and specificity (97%) using cut-off values from 36 to 40 IU/L. The included studies were homogeneous. Optimal cut-off point was determined at 39 IU/L, and LRs were 26.8 and 0.038 for values above and below this cut-off., Conclusions: This study supports the proposition that ADA determination is a fast and discriminating test for diagnosing PTB with an optimal cut-off value of 39 IU/L.

Pulmonary hypertension due to chronic pulmonary thromboembolism is frequently underdiagnosed and has a very poor prognosis if untreated. When the presence of central pulmonary artery thrombus is confirmed, thromboendarterectomy is the treatment of choice, with very good results. We report a 28 years old male with two previous episodes of deep venous thrombosis (DVT) who was admitted due to 8 months of progressive shortness of breath and a syncope. He underwent a CT pulmonary angiogram and an echocardiogram. Severe pulmonary hypertension was confirmed, secondary to a chronic pulmonary thromboembolism with an overlapped acute component. He received systemic thrombolysis with partial thrombus disappearance. Therefore a pulmonary thromboendarterectomy was performed and an inferior vena cava filter was placed. The patient was discharged with marked improvement in his functional capacity.

Objective: To compare the safety and clinical outcomes of enteral and parenteral nutrition in patients with acute pancreatitis., Data Sources: Medline, Embase, Cochrane controlled trials register, and citation review of relevant primary and review articles., Study Selection: Randomized controlled studies that compared enteral nutrition with parenteral nutrition in patients with acute pancreatitis. From 117 articles screened, six were identified as randomized controlled trials and were included for data extraction., Data Extraction: Six studies with 263 participants were analyzed. Descriptive and outcome data were extracted. Main outcome measures were infections, complications other than infections, operative interventions, length of hospital stay, and mortality. The metaanalysis was performed with the random effects model., Data Synthesis: Enteral nutrition was associated with a significantly lower incidence of infections (relative risk 0.45; 95% confidence interval 0.26 to 0.78, P= 0.004), reduced surgical interventions to control pancreatitis (0.48, 0.22 to 1.0, P= 0.05), and a reduced length of hospital stay (mean reduction 2.9 days, 1.6 days to 4.3 days, P <0.001). There were no significant differences in mortality (relative risk 0.66, 0.32 to 1.37, P = 0.3) or non-infectious complications (0.61, 0.31 to 1.22, P= 0.16) between the two groups of patients., Conclusions: Enteral nutrition should be the preferred route of nutritional support in patients with acute pancreatitis.

The severity and duration of post chemotherapy neutropenia were recognized during the 1960s as main predisposing factors for infections in cancer patients. At the beginning of the 70's a standard management approach for all febrile neutropenia (FN) episodes was proposed, based on hospitalization and intravenous empirical broad spectrum antibiotic therapy. Widespread use of this approach resulted in a significant reduction in mortality attributable to bacterial infections. During the last 10 to 15 years, reappraisal of this standard approach has been done by several research groups who question the benefit of treating all FN patients similarly without taking in to consideration differences in severity of the FN episodes. This reappraisal has led during the 1990s to the development of the concept of high and low risk FN episodes that has been the base for the adoption of selective therapies based on the risk categorization of the individual patient. The Chilean Infectious Diseases Society called upon two government National Programs responsible for the appropriate distribution of chemotherapeutic drugs to all pediatric and adults cancer patients within the public health system, and upon the Chilean Hematology Society for the development of a Consensus on Diagnosis, Treatment and Prevention of Infections during FN Episodes in Cancer patients. The need for this Consensus is based on two main aspects: the new approaches proposed during the past year for management of these episodes, and the increasing population of cancer patients receiving improved chemotherapeutic agents that has increased there survival possibilities as well as there possibility to suffer a FN episode. The topics discussed in this document are based on an updated systematic and analytic review of the medical literature including epidemiology, laboratory diagnostics, risk categorization, treatment and prophylaxis. National data was included when available in order to provide the healthcare personnel that take care of these patients with best evidence based recommendations adjusted to the Chilean reality.

Evidence based medicine (EBM) appeared early in the 1990s and since then it has been developed and expanded worldwide. A decade later we summarize the history of EBM, the initial debates and the evolution to the current concept of evidence based health care (EBHC) as a tool for clinical decision making. We also describe the process of EBHC, some insights to current dilemmas and the situation of EBM in Chile.

Background: Although clinicians sometimes choose amiodarone to convert atrial fibrillation (AF) to sinus rhythm, no current and comprehensive systematic review has summarized its effectiveness., Objective: To review the effectiveness of amiodarone in converting AF to sinus rhythm over a 4-week period., Methods: Two reviewers conducted a systematic search for randomized trials in databases, complemented by hand searches and contact with experts. Selected trials compared amiodarone with placebo, digoxin, or calcium channel blockers for conversion of AF to sinus rhythm. Reviewers evaluated the methodology and extracted data from each primary study., Results: Twenty-one studies met eligibility criteria. Duration of AF proved to be a source of heterogeneity, leading to 2 analyses. The relative risk (RR) for achieving sinus rhythm was 4.33 (95% confidence interval [CI], 2.76-6.77) for trials with mean AF duration of greater than 48 hours and 1.40 (95% CI, 1.25-1.57) for those with AF of 48 hours or less. The risk differences for these 2 groups were 27% and 26%, respectively, yielding a number needed to treat of 4 for both groups. The low control event rate among trials with long duration of AF, compared with that of trials with a duration of 48 hours or less, explained the difference in the RR for conversion. We found that the size of the left atrium, presence of cardiovascular disease, and protocols of amiodarone administration did not influence the magnitude of effect. Serious adverse events were infrequent., Conclusions: Amiodarone is effective for converting AF to sinus rhythm in a wide range of patients. Although use of amiodarone is apparently safe, safety data are too scarce for definitive conclusions.

Objectives: Trunk position at 45 degrees from the horizontal is associated with a decreased risk of gastroesophageal aspiration. The objectives of this study were to determine the accuracy of trunk flexion estimates compared to a reference standard measurement, and to determine agreement about trunk flexion among ICU clinicians., Design: Prospective observational study., Setting: Two university-affiliated medical-surgical ICUs., Patients and Participants: Thirty-three mechanically ventilated ICU patients, seven residents, two fellows, three intensivists, and twenty-eight bedside nurses., Interventions: Prospectively, concurrently, and independently during rounds, one bedside nurse, one resident, one fellow, and one intensivist clinically estimated the trunk flexion of mechanically ventilated patients. To record the reference standard, a trained investigator measured trunk position in the vertical plane using a goniometer., Measurements and Results: We made 438 clinical assessments on 33 patients aged 57.2+/-19.4 (SD) years with an APACHE II score of 27.3+/-9.4. Mean trunk flexion estimates were: nurses 24.3+/-12.3 degrees from the horizontal, residents 20.2+/-13.7, fellows 20.3+/-10.8, and intensivists 21.1+/-13.1 compared to the reference standard measurement 16.2+/-9.0 degrees. The accuracy of trunk flexion estimates was fair to moderate [intraclass correlation for reference standard versus nurses (ICC 0.42), residents (ICC 0.52), fellows (ICC 0.36), and intensivists (ICC 0.55)]. The agreement among different groups of clinicians was moderate., Conclusions: In mechanically ventilated patients, we found that clinical estimates of trunk position were moderately good, agreement amongst caregivers was moderately good, but that all clinicians tended to overestimate the angle of semirecumbency.

Background: An important increase in health care costs has occurred lately, determined in part by the expenses of intensive care units. An important proportion of beds in these units are occupied by elders, with high costs and dubious results., Aim: To study the survival of elderly patients in intensive care units to shed light on the question if these patients should be admitted to these facilities., Material and Methods: We retrospectively analyzed the mortality of 443 patients older than 65 years old, admitted to an intensive care unit between 1993 and 1994. The mortality was compared with that of 334 younger patients admitted in the same period. Severity of disease was determined using admission APACHE II score., Results: Older patients had a higher admission APACHE score than younger subjects (18.4 +/- 8.4 and 14.5 +/- 8.7 respectively, p < 0.01). Mortality during the intensive care unit stay was similar in older and younger patients (18.5 and 14.4%, respectively). Hospital mortality was also similar (22.4 and 25.9%, respectively). Older patients had a higher frequency of chronic diseases and degree of functional impairment. Mortality rates for different diseases were also similar in older and younger patients., Conclusions: Older age was not associated with a higher mortality during intensive care unit stay. Prognosis is determined by the admission severity score and the number of concomitant chronic diseases.

Background: Lately, we have observed an increase in the admission to intensive care units of patients over 65 years old, probably due to the increase in life expectancy that is occurring in Chile., Aim: To compare the frequency of admissions to intensive care units in patients over 65 years old, their diagnoses, their severity and hospital course, with those of younger patients., Patients and Methods: The charts of all patients admitted to an intensive care unit of a University Hospital, during one year, were reviewed. The diagnosis that caused the admission was considered the main disease. Severity at the moment of admission was assessed using the Apache score., Results: A total of 777 patients were admitted during the study period. Twenty had to be excluded due to lack of reliable data. Four hundred thirty two (57%) were over 65 years old. Cardiovascular diseases were the main cause of admission in young and old patients. Mortality was 14.8% of patients over 65 years old and 18.7% in younger patients. Main causes of death were cardiac arrest, cardiogenic shock, sepsis and cerebrovascular disease. No differences in causes of death were observed between young and old patients., Conclusions: Patients older than 65 years old admitted to intensive care units are very similar to their younger counterparts in their prognosis and causes of admission.

Aim: To assess the acute effects of methylene blue infusion, an inhibitor of nitric oxide synthesis, on hemodynamic parameters in patients with refractory septic shock., Patients and Methods: Fourteen patients admitted to intensive care units with septic shock of diverse etiologies and unable to maintain median arterial pressures over 60 mm Hg with the use of at least 2 vasoactive drugs, were studied. All received a 1 mg/kg bolus of methylene blue Hemodynamic parameters were measured before and 30, 60, 120 and 180 min after the bolus., Results: Systolic and diastolic blood pressure and systemic vascular resistance increased in all patients. There were no significant changes in cardiac output, oxygen consumption or extraction., Conclusions: Methylene blue has an acute pressor effect in patients with septic shock.

Ectopic implantation of the embryo in the tube opposite to the ovary containing the corpus luteum constitutes evidence of peritoneal or uterine transmigration of the egg. The frequency of this phenomenon was reinvestigated utilizing histopathologic confirmation of the side of the corpus luteum. A tubal pregnancy contralateral to the ovulating ovary was found in 28% of 67 cases, indicating that either the oocyte, the zygote or the embryo had entered the tube in which implantation took place from a medial site such as the peritoneal or the uterine cavity rather than directly from the ovulating ovary. Assuming that once in the medial site there is equal chance of entering either tube, it follows that in 56% of tubal pregnancies the egg has entered the tube from a midline location. Attempts to recover the oocyte from the tubes in normal women were successful in fewer than 5% of cases contralateral to the corpus luteum. It is concluded that tubal pregnancy is associated with a significant increase in the occurrence of transmigration of the egg.