Adjuvant endocrine therapy in HER2-positive breast cancer patients: systematic review and meta-analysis.

BACKGROUND: Approximately 50% of human epidermal growth factor receptor 2 (HER2)-positive breast cancer lesions express hormone receptors. These tumors present a unique therapeutic challenge, and the optimal endocrine therapeutic approach remains controversial. We aimed to study the optimal adjuvant endocrine therapy in this setting, to better establish the basis for clinical recommendations in HER2-positive disease. METHODS: We conducted a literature search up to May 2020, in which we identified randomized controlled trials (RCTs) that investigated the efficacy of various adjuvant hormonal therapies among premenopausal and postmenopausal patients with hormone receptor (HR)-positive, HER2-positive early breast cancer. Disease-free survival (DFS) was calculated with the random effect model and hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Six RCTs (N = 5390 patients) were included in the final analysis. There was no significant difference in DFS between adjuvant treatment with aromatase inhibitors and tamoxifen (HR 0.99, 95% CI 0.68-1.44, P = 0.96). Furthermore, after omitting the ALTTO trial, as it did not randomize patients to hormonal therapy, no significant difference was observed between the two protocols (HR 1.06, 95% CI 0.65-1.73, P = 0.81). CONCLUSION: Our study demonstrates similar DFS with tamoxifen and aromatase inhibitors as adjuvant endocrine treatment in HER2-positive HR-positive early-stage breast cancer patients. Future larger prospective studies focusing on the various contemporary endocrine regimens are warranted to validate our findings.

Evaluation of a prospectively administered written questionnaire to reduce the incidence of suspected latex anaphylaxis during elective cesarean delivery.

BACKGROUND: Life-threatening anaphylaxis has been reported in women exposed to latex during surgery. We compared a written screening questionnaire to identify suspected latex sensitivity with a verbal inquiry used previously in a historical control group of women undergoing cesarean delivery to determine if the incidence of suspected latex anaphylaxis could be reduced. METHODS: To identify suspected latex sensitivity among women undergoing elective cesarean delivery in a single-site tertiary unit, a nine-item written screening questionnaire was compared to historical use of a standard verbal inquiry "Are you allergic to medications or latex?". Women who had suspected latex sensitivity risk factors, or who had known latex allergy, underwent latex-free surgery. Women with suspected anaphylaxis during cesarean delivery were recommended to undergo allergen testing. The primary study outcome was suspected anaphylaxis incidence during the two periods: historical control January to December 2008, questionnaire March 2010 to April 2011. RESULTS: The questionnaire identified suspected latex sensitivity in 66 of 453 women (14.6%) who completed the questionnaire. The standard verbal inquiry group had identified 12 of 460 women (2.6%) with self-reported latex sensitivity. The incidence of suspected anaphylaxis during cesarean delivery was significantly lower during the questionnaire period when compared to historical controls (3/516, 0.6% vs. 11/460, 2.4%, P=0.015). For both groups, 13 of 14 women (92.9%) with suspected latex anaphylaxis were contactable; five of 13 (38.5%) had undergone allergen testing and all were positive for latex. CONCLUSIONS: Use of the written screening questionnaire was associated with fewer cases of suspected anaphylaxis during cesarean delivery compared with the historical control. Most women with suspected anaphylaxis did not perform allergy testing; however, all who did were positive for latex.

The use of a standard design medication room to promote medication safety: organizational implications.

QUALITY PROBLEM: Medication administration is one of the most potentially dangerous tasks in hospitals. In recent years, the medical establishment has gained insight into the importance of environmental and ergonomic factors on patient safety. Limited data are available on how a standard designed medication room (MR) supports safety medication administration. INITIAL ASSESSMENT: Proactive observations were conducted at a tertiary care facility, the Hadassah University Medical Center, Jerusalem, Israel, to determine if safety principles were being implemented in the medication preparation and storage environment. These observations revealed that no designated MRs existed in the hospitals wards and safety systemic weaknesses in medication preparation. CHOICE OF SOLUTION: Guidelines for planning and designing MRs, based on safety and human engineering principles, were established to promote safer medication administration in hospital wards. IMPLEMENTATION: The purpose of the survey was to compare the implementation of safety principles among hospital wards before and after MR renovation and among hospital wards with and without a MR. Structured observations in medication preparation areas and storage were designed. Selected safety indicators were measured (e.g. ordering and labeling; storage of intravenous infusions). Each category was subdivided into indicators that were design dependent only (DD), design and behavior dependent (DBD) and behavior dependent only (BD). EVALUATION: Indicators that were both DD and DBD showed significant improvement before and after renovation of MRs. Most of the results were not significant for BD indicators. A similar trend was observed in departments with and without a MR. A trend of improvement could be seen in BD-positive indicators, regardless of the presence or absence of a dedicated MR. LESSONS LEARNED: A standard design MR can improve environmental aspects of safety medication administration.

Emergency room visit: a red-flag indicator for poor diabetes care.

AIM: To determine the association between emergency room (ER) admission and quality of diabetes care in the community. METHODS: In a nested case-control study of patients with Type 2 diabetes mellitus (DM) within a large health maintenance organization (HMO) in Israel, 919 patients who were admitted to one of West Jerusalem's ERs between 1 May and 30 June 2004 were compared with 1952 control subjects not admitted. Data on study covariates were retrieved from the HMO's computerized database and a subset of the study population was interviewed. Logistic regressions were conducted to estimate the odds ratios of being admitted according to different measures of quality of care, controlling for socio-demographic variables, co-morbidities and type of DM treatment. RESULTS: The main indices of quality of primary care that were inversely associated with visiting an ER during the study period included performance of a cholesterol test in the year prior to the index date [adjusted odds ratio (OR) 0.23, 95% confidence interval (CI) 0.19-0.29, P < 0.001], performance of glycated haemoglobin test (OR 0.26, 95% CI 0.24-0.29, P < 0.001), visiting an ophthalmologist (OR 0.47, 95% CI 0.32-0.68, P = 0.001), and recommendations to stop smoking (OR 0.10, 95% CI 0.05-0.21, P < 0.001). CONCLUSIONS: Admission to the ER can be used as an indicator for poor quality of diabetes care. There is an association between ER admission and poor quality of diabetes care.

Limited value of physical examinations in upper respiratory illness: account of personal experience and survey of doctors' views.

UNLABELLED: Medical tradition considers a physical examination (PE) an essential part of the clinical encounter. In real medical practice, however, a full PE may not be necessary when the diagnosis is clear after anamnesis and general impression. We assessed the value of PEs in 500 diagnoses of upper respiratory infection (URI) and the attitudes of 123 doctors regarding the utility of PEs in virtual cases. METHODS: Computerized files of consecutive cases with a diagnosis of URI over 8 months in two practices were reviewed and correlation studies between the extent of PE and clinical outcomes were performed. In addition, doctors' attitudes and declarations about PEs were compared. RESULTS: Five hundred paediatric and adult patients were included. Less than one-fifth underwent a full PE. More patients who underwent a full PE returned because they still felt unwell or their parents felt they were unwell. Fewer doctors declared actually having performed PEs than supported giving one in two virtual cases of URI. Specialized doctors were less inclined to perform PEs than doctors without a specialization. CONCLUSIONS: Our study suggests that in many cases presenting as URI, doctors may conduct limited PEs or even omit them entirely.

Breast reconstruction: complication rate and tissue expander type.

BACKGROUND: Limited literature exists regarding complication rates among women undergoing breast reconstruction and the association of these rates with tissue expander types (anatomic, round and Becker). METHODS: A historical cohort study investigated all breast reconstructions performed at Hadassah Medical Center for 140 consecutive women. Analyses were performed using both logistic and Poisson regression multivariate methods. RESULTS: At least one major complication occurred in each of the following groups: anatomic (41%), round (20%), and Becker (11.7%) (p = 0.015). Women reconstructed with anatomic expanders were at increased risk for at least one complication (odds ratio [OR], 3.96; 95% confidence interval [CI], 1.18-13.3; p = 0.026) and an average increase of 331% (95% CI, 102-817%; p = 0.0002) in the number of major complications. CONCLUSION: The results of this study suggest that integrated-valve expanders are associated with more complications than the distant inflation port. The benefits of an anatomic shape may perhaps be better exploited using devices with a distant port.

Insoles for prevention and treatment of back pain.

BACKGROUND: There is lack of theoretical and clinical knowledge of the use of insoles for prevention or treatment of back pain. The high incidence of back pain and the popularity of shoe insoles call for a systematic review of this practice. OBJECTIVES: To determine the effectiveness of shoe insoles in the prevention and treatment of non-specific back pain compared to placebo, no intervention, or other interventions. SEARCH STRATEGY: We searched the following databases: The Cochrane Back Group Trials Register and The Cochrane Central Register of Controlled Trials (CENTRAL) to March 2005, and MEDLINE, EMBASE, and CINAHL to February 2007; reviewed reference lists in review articles, guidelines and in the included trials; conducted citation tracking; contacted individuals with expertise in this domain. SELECTION CRITERIA: We included randomized controlled trials that examined the use of customized or non-customized insoles, for the prevention or treatment of back pain, compared to placebo, no intervention or other interventions. Study outcomes had to include at least one of the following: self-reported incidence or physician diagnosis of back pain; pain intensity; duration of back pain; absenteeism; functional status. Studies of insoles designed to treat limb length inequality were excluded. DATA COLLECTION AND ANALYSIS: One review author conducted the searches and blinded the retrieved references for authors, institution and journal. Two review authors independently selected the relevant articles. Two different review authors independently assessed the methodological quality and clinical relevance and extracted the data from each trial using a standardized form. MAIN RESULTS: Six randomized controlled trials met inclusion criteria: Three examined prevention of back pain (2061 participants) and three examined mixed populations (256 participants) without being clear whether they were aimed at primary or secondary prevention or treatment. No treatment trials were found. There is strong evidence that the use of insoles does not prevent back pain. There is limited evidence that insoles alleviate back pain or adversely shift the pain to the lower extremities. LIMITATIONS: This review largely reflects limitations of the literature, including low quality studies with heterogeneous interventions and outcome measures, poor blinding and poor reporting. AUTHORS' CONCLUSIONS: There is strong evidence that insoles are not effective for the prevention of back pain. The current evidence on insoles as treatment for low-back pain does not allow any conclusions.High quality trials are required for stronger conclusions.

Attitudes of medical practitioners towards "Do Not Resuscitate" orders.

When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.

Prevention of perioperative venous thromboembolism and coronary events: differential responsiveness to an intervention program to improve guidelines adherence.

INTRODUCTION: Prevention of venous thromboembolism and coronary events (with beta-blockers) during and after surgery is at the top of a list of safety practices for hospitalized patients, recommended by the Agency for Health Care Research and Quality (AHRQ). We wished to determine and improve adherence to clinical guidelines for these topics in our institution. PATIENTS, MATERIAL, AND METHODS: A prospective survey was conducted over several weeks on operated patients in a 1200-beds medical center (a teaching, community and referral hospital in Jerusalem, Israel). Eligibility for and actual administration of prophylactic treatment with anticoagulant and beta-blockers were determined. Following an intervention program, which included staff meetings, development of local protocols, and academic detailing by a nurse, the survey was repeated. RESULTS: In general, adherence to recommended anticoagulation prophylaxis was low, found in only 29% [95% confidence interval (CI) = 23-36] of eligible patients. After the intervention, adequate anticoagulation increased to 50% (95% CI = 40-59) of eligible patients (P < 0.001). Initiation of beta-blockers in preventing perioperative cardiac events was very low (0%, 95% CI = 0-5%) and did not increase after intervention. CONCLUSIONS: Adherence to guidelines for prevention of surgical complications was found to be low in our institution. A multifaceted intervention significantly increased use of prophylaxis for venous thromboembolism but not for coronary events. This differential response suggests that the success of a quality improvement project strongly depends on topic content and its phase of acceptance.

Cyclosporine A for induction of remission in severe ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Approximately 15% of patients have a severe attack requiring hospitalization at some time during their illness. These patients are traditionally treated with intravenous corticosteroids, with a response rate of approximately 60%. The patients who do not respond to steroid treatment usually require surgical removal of the large bowel (proctocolectomy or colectomy with an anal pouch). This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis. Few alternative treatments exist for severe ulcerative colitis: immunosuppressive medications (such as azathioprine) have a slow onset of action and are therefore usually ineffective. Antibiotics are not proven to be effective and biological treatments such as infliximab are still under investigation. The introduction of cyclosporine-A (CsA) for use in patients with severe ulcerative colitis (UC) has provided an alternative to patients previously facing only surgical options. Cyclosporine acts mainly by inhibiting T lymphocyte function, which is essential for the propagation of inflammation. Unlike most other immunosuppressive agents, CsA does not suppress the activity of other hematopoietic cells, does not cause bone marrow suppression and has a rapid onset of action. This reviews aims to systematically assess the effectiveness and safety of CsA for severe UC. OBJECTIVES: This review aimed to evaluate the effectiveness of cyclosporine A for patients with severe ulcerative colitis. SEARCH STRATEGY: Electronic searches of The Cochrane Library (Issue 1, 2004), EMBASE (1980-2004), and MEDLINE (1966-2004); hand searching the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised clinical trials comparing cyclosporine A with placebo or no intervention to obtain and maintain remission of idiopathic ulcerative colitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat analysis for the outcome measures. MAIN RESULTS: Only two randomized controlled trials were identified that satisfied the inclusion criteria. These two trials could not be pooled for analysis because of major differences in design and patient populations. In the first trial, 11 patients received intravenous cyclosporine (4 mg/kg) and 9 received placebo. Two of 11 in the treatment group failed to respond to therapy compared with nine of nine in the placebo group (RR 0.18, 95% CI 0.05 - 0.64). However, 3/11 and 4/9 eventually underwent colectomy in the treatment and placebo groups respectively and follow-up was less than a month. In the second trial 15 patients were treated with intravenous cyclosporine and 15 with intravenous methylprednisolone. Five of 15 patients in the cyclosporine group failed to respond to therapy as compared to 7/15 in the methylprednisolone group (RR 0.71, 95% CI 0.29 - 1.75). After 1 year 7/9 responders in the cyclosporine group were still in remission compared with 4/8 in the steroid group (p > 0.05) and the colectomy rate was similar in both groups. The mean time to response in the cyclosporine group in the 2 trials was short (7 days and 5.2 days). These results should be interpreted with caution given the small numbers of trials and patients evaluated for comparison, and limited follow-up (few weeks in one trial to a year in the other). The precise assessment of the occurrence of adverse events was difficult because the trials described different adverse reactions, which reversed after discontinuation of cyclosporine. There was no evidence in the trials reviewed that cyclosporine was more effective than standard treatment for preventing colectomy but this effect cannot be excluded due to the small sample size and rarity of this outcome. Additional limitations of current research include lack of data on quality of life, costs and long-term results of cyclosporine therapy. AUTHORS' CONCLUSIONS: There is limited evidence that cyclosporine is more effective than standard treatment alone for severe ulcerative colitis. The relatively quick response makes the short-term use of cyclosporine potentially attractive, but the long-term benefit is unclear, when adverse events such as cyclosporine-induced nephrotoxicity may become more obvious. There is a need for additional research on quality of life, costs and long-term results from cyclosporine therapy in severe ulcerative colitis.

Interactive learning in medicine: socrates in electronic clothes.

Traditional lectures have limited ability to maintain attention and to promote changes in behaviour. Active learning, which stimulates the audience to think and participate, may be more effective. We describe our experience with an interactive polling system in lectures to physicians and students. Audience's answers to questions are displayed, providing instant feedback to both lecturer and audience, and promoting the use of case discussions and problem-solving exercises. In our experience, this modality improves the quality of clinical learning and deserves further evaluation.

Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials.

BACKGROUND: Antibiotic prophylaxis has been reported to decrease bacterial infections and fatality rates in inpatients with cirrhosis. We performed a systematic review to evaluate the efficacy of antibiotic prophylaxis in inpatients with cirrhosis, regardless of the underlying risk factors that led to hospital admission. METHODS: A comprehensive literature search strategy was performed including the Cochrane Library, Embase, Medline, a manual search of bibliographic references, and contacting the authors of each included trial. We included any randomized clinical trial comparing different types of antibiotic prophylaxis with placebo or no intervention in inpatients with cirrhosis. Two reviewers independently applied the selection criteria to all identified references, appraised the methodological quality of each trial and extracted the relevant data. Relative risks and 95% confidence intervals were estimated using the fixed effect model. A test of heterogeneity and a funnel plot were performed and an intention-to-treat approach was used for the outcome measures. RESULTS: Nineteen randomized trials were identified, 13 of which were included in the review. A significant beneficial effect on mortality (RR: 0.70; 95% CI: 0.56, 0.89) and prevention of bacterial infections (RR: 0.39; 95% CI: 0.32, 0.48) was observed, regardless of the underlying risk factors. Few adverse events were reported and there was no heterogeneity between studies. We identified a funnel plot asymmetry for the included trials. CONCLUSIONS: Antibiotic prophylaxis for inpatients with cirrhosis is efficacious in reducing the number of deaths and bacterial infections regardless of the underlying risk factors.

Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding.

BACKGROUND: Bacterial infections are a frequent complication in patients with cirrhosis and gastrointestinal bleeding. Antibiotic prophylaxis seems to decrease the incidence of bacterial infections. Oral antibiotics, active against enteric bacteria, have been most often used as antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding. OBJECTIVES: This review aims to evaluate the effects of antibiotic prophylaxis in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. SEARCH STRATEGY: Electronic searches on The Cochrane Hepato-Biliary Group Controlled Trials Register (May 2001), The Cochrane Library (Issue 2, 2001), EMBASE (1980-2001), and MEDLINE (1966-2001); handsearching the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised clinical trials comparing different types of antibiotic prophylaxis with placebo, no intervention, or another antibiotic to prevent bacterial infections in cirrhotic patients with gastrointestinal bleeding. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat basis for the outcome measures. MAIN RESULTS: Eight trials evaluated the effects of antibiotic prophylaxis compared with placebo or no antibiotic prophylaxis in 864 patients. A significant beneficial effect on decreasing mortality (RR 0.73, 95% CI 0.55 to 0.95) and the incidence of bacterial infections (RR 0.40, 95% CI 0.32 to 0.51) was observed. No serious adverse events were reported. The trials showed no significant heterogeneity. Three additional trials evaluated the effects of antibiotics compared with a different regimen of antibiotics in 503 patients. Data could not be combined as each trial used different interventions. None of the examined antibiotic regimens was superior to the control regimen regarding mortality or the incidence of bacterial infections. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis for cirrhotic inpatients with gastrointestinal bleeding is efficacious in reducing the number of deaths and bacterial infections, are well tolerated, and should be advocated.

Antibiotics for spontaneous bacterial peritonitis in cirrhotics.

BACKGROUND: Spontaneous bacterial peritonitis is mainly a complication of cirrhotic ascites that occurs in the absence of any intra-abdominal, surgically treatable source of infection. Antibiotics have been recommended as the mainstay treatment for spontaneous bacterial peritonitis. However, this recommendation is not based on convincing evidence. It has been proposed that treatment should cover Gram-negative enteric bacteria and Gram-positive cocci, that are responsible for up to 90% of cases. OBJECTIVES: To evaluate the effectiveness and safety of different types and ways of antibiotic therapy for spontaneous bacterial peritonitis in cirrhotic patients. SEARCH STRATEGY: Electronic searches on the Cochrane Library (Issue 3, 2000), the Cochrane Hepato-Biliary Group Trials Register (March 2000), EMBASE (1980-2000), MEDLINE (1966-2000); scanning the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised trials comparing different types of antibiotics for spontaneous bacterial peritonitis in cirrhotic patients. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative risks or weighted mean differences, with their 95% confidence intervals were estimated using 'intention-to-treat' analyses. MAIN RESULTS: Nine trials dealing with 684 patients diagnosed with spontaneous bacterial peritonitis were included. No placebo-controlled trial was found. Each of the included trials compared different antibiotics, and no meta-analysis could be performed. We were unable to establish the optimal dose or duration of antibiotic therapy and found no convincing evidence that cefotaxime is more effective than ampicillin-tobramycin or that oral quinolones should be recommended for patients with less severe manifestations of the disease. REVIEWER'S CONCLUSIONS: This review provides no clear evidence for the treatment of cirrhotic patients with spontaneous bacterial peritonitis. Until large, well-conducted, trials provide adequate evidence, treatment must be based on clinical experience.

Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.

The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.