Risk-benefit Discussion Research Articles

Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death: A Science Advisory From the American Heart Association.

Sudden cardiac death (SCD) accounts for >300 000 deaths in the United States annually.1 Although the majority of these deaths occur in low-risk populations2 in which aggressive interventions are not practical, some higher-risk populations have been established in whom intervention with an implantable cardioverter-defibrillator (ICD) has been shown in randomized trials to reduce mortality.3–7 Additionally, there is a population of patients who may benefit from automatic emergency cardioversion-defibrillation but are not deemed appropriate candidates for ICD implantation at the time of presentation. This group is defined by 2 populations. The first subgroup comprises those who are at perceived risk but for whom there may be optimism for clinical improvement (eg, patients soon after revascularization or those with a recent diagnosis of myocardial infarction [MI] or cardiomyopathy). Alternatively stated, the optimal management of these patients at risk (or perceived risk) during the waiting period before an ICD is indicated remains unknown. The second subgroup includes those who have a clear indication for ICD but also have a contraindication to immediate ICD placement (eg, active infection or unknown prognosis). The wearable cardioverter-defibrillator (WCD) is a device designed for patients at risk of SCD who are not immediate candidates for ICD therapy. By providing automatic therapy, the WCD does not depend on a second person to defibrillate, as required with a manual or automated external defibrillator (AED). Unlike the ICD (including both transvenous and subcutaneous devices), the WCD requires no surgical operation, can be provided for a short period of time, is temporary, and is easily removed. These characteristics of the WCD, along with safety and efficacy data presented to the US Food and Drug Administration (FDA), resulted in approval in the United States in 2002.8 Because of the increasing use of the WCD and uncertainty of indications …

Vigorous Sport and Health in Middle-Aged Adults – Do we Need a Risk-Benefit Discussion?

Vigorous Sport and Health in Middle-Aged Adults – Do we Need a Risk-Benefit Discussion?

SAFETY PROFILE OF OCRIPLASMIN FOR SYMPTOMATIC VITREOMACULAR ADHESION: A Comprehensive Analysis of Premarketing and Postmarketing Experiences.

After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.

GAO: Reduce Antipsychotic Use in Older Dementia Patients

The Department of Health & Human Services should do more to curb antipsychotic use in older adults with dementia, according to a recent report by the Government Accountability Office. About 33% of older adults with dementia who resided in a nursing home and were enrolled in Medicare Part D plans were prescribed antipsychotics, the authors said. Among those who did not reside in a nursing home, 14% were prescribed antipsychotics. PA/LTC PerspectiveMy read on this is that CMS is reluctant to extend its authority into environments where it may pay for some drugs, but not for care. The issue of off-label prescribing becomes an even more slippery slope in the nonregulated environments and further erodes the doctor-patient relationship. We should always be mindful that guidelines are suggestions and not rules, and clinical practice has always had a large element of adaptation to the situation at hand. Hopefully, prescribers carry on an even more intense risk-benefit discussion with patients and their families when these drugs are used in settings other than the nursing home, and disclose current thinking on the topic.—Eric G. Tangalos, MD, AGSF, CMDMayo ClinicRochester, MN My read on this is that CMS is reluctant to extend its authority into environments where it may pay for some drugs, but not for care. The issue of off-label prescribing becomes an even more slippery slope in the nonregulated environments and further erodes the doctor-patient relationship. We should always be mindful that guidelines are suggestions and not rules, and clinical practice has always had a large element of adaptation to the situation at hand. Hopefully, prescribers carry on an even more intense risk-benefit discussion with patients and their families when these drugs are used in settings other than the nursing home, and disclose current thinking on the topic. —Eric G. Tangalos, MD, AGSF, CMD Mayo Clinic Rochester, MN The investigation also found that 23% of short-stay [100 days or fewer] nursing home residents were prescribed antipsychotics, compared with 33% of long-stay residents. Sixty-six percent of the antipsychotic prescriptions for Medicare Part D patients were prescribed by internists and family medicine physicians, and 16% were written by psychiatrists or neurologists, according to the report. Meanwhile, 5% of the antipsychotics for these patients were prescribed by nurse practitioners and physician assistants, and the rest were prescribed by many specialties. Although several HHS programs aim to reduce antipsychotic use in aging populations, these efforts are limited to adults in nursing homes, who likely have greater disease severity. “Similar efforts have not been directed toward caregivers of older adults living outside of nursing homes, such as those in assisted living facilities and private residences,” the authors said. “Targeting this segment of the population is equally important given that over 1.2 million Medicare Part D enrollees living outside of nursing homes were diagnosed with dementia in 2012 and Medicare Part D pays for antipsychotic drugs prescribed to these individuals,” they added. By expanding its outreach and educational efforts, HHS might be able to reduce the unnecessary reliance on antipsychotics for treating the “behavioral symptoms of dementia for all older adults regardless of their residential setting,” according to the report.

Radiation Exposure from Imaging Tests in Pediatric Emergency Medicine: A Survey of Physician Knowledge and Risk Disclosure Practices

BackgroundDisclosing potential future malignancy risks from diagnostic tests that expose children to ionizing radiation in the emergency department may be challenging. ObjectivesWe determined the proportion of pediatric emergency medicine (PEM) physicians who are aware of current malignancy risk estimates associated with head computed tomography (CT). We also examined reported risk and strategy disclosure practice patterns. MethodsWe conducted an online survey of members of a national Canadian PEM physician association using a modified Dillman's technique. ResultsOf 156 eligible participants, 126 (80.8%) responded to the survey. Of the 126 respondents, 124 (98.4%; 95% confidence interval [CI] 96.2–100) reported that there is a potential malignancy risk associated with head CT, and 46 (36.5%; 95% CI 28.1–44.9) correctly identified the best current estimate of this risk. The majority, 68.8% (95% CI 60.7–76.9), reported disclosing these possible risks “most of the time/almost always.” Although some physicians reported varying their strategy with the clinical scenario, the most frequently selected disclosure strategies were a comparison with chest radiographs and everyday risks. Frequently cited barriers to informed risk-benefit discussions were concerns that parents will worry excessively about cancer (27.8%), discussions during the treatment of a critically ill child (23.8%), and a concern that parents may not want the test (15.9%). ConclusionsApproximately one-third of pediatric emergency physicians were able to identify the best available estimate of the malignancy risk from a head CT. Although there are some barriers, many PEM physicians report regularly participating in risk-benefit disclosures.

Content and Style of Radiation Risk Communication for Pediatric Patients

The diagnostic benefits of medical imaging, including CT, must be weighed against the risks of ionizing radiation and communicated effectively to patients. Health care providers requesting and performing these examinations have a shared responsibility for this risk-benefit discussion. Effective and balanced communication of these risks requires style as well as content mastery. Fundamentals of communication are similar for all patients, but special attention is needed in the pediatric setting.

Prescription Opioid Analgesics Increase the Risk of Depression

Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations. The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression. Retrospective cohort study, new user design. Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000. Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007. Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90-180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05-1.46 for 90-180 days, and HR = 1.51; 95 % CI:1.31-1.74 for > 180 days). In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.

Donor risk index for African American liver transplant recipients with hepatitis C virus

African American (AA) liver transplant (LT) recipients with hepatitis C virus (HCV) have higher rates of graft loss than other racial/ethnic groups. The Donor Risk Index (DRI) predicts graft loss but is neither race- nor disease-specific and may not be optimal for assessing donor risk for AA HCV-positive LT recipients. We developed a DRI for AA with HCV with the goal of enhancing graft loss predictions. All U.S. HCV-positive adult AA first deceased donor LTs surviving ≥30 days from March 2002 to December 2009 were included. A total of 1,766 AA LT recipients were followed for median 2.8 (interquartile range [IQR] 1.3-4.9) years. Independent predictors of graft loss were donor age (40-49 years: hazard ratio [HR] 1.54; 50-59 years: HR 1.80; 60+ years: HR 2.34, P < 0.001), non-AA donor (HR 1.66, P < 0.001), and cold ischemia time (CIT) (HR 1.03 per hour >8 hours, P = 0.03). Importantly, the negative effect of increasing donor age on graft and patient survival among AAs was attenuated by receipt of an AA donor. A new donor risk model for AA (AADRI-C) consisting of donor age, race, and CIT yielded 1-year, 3-year, and 5-year predicted graft survival rates of 91%, 77%, and 68% for AADRI <1.60; 86%, 67%, and 55% for AADRI 1.60-2.44; and 78%, 53%, and 39% for AADRI >2.44. In the validation dataset, AADRI-C correctly reclassified 27% of patients (net reclassification improvement P = 0.04) compared to the original DRI. AADRI-C identifies grafts at higher risk of failure and this information is useful for risk-benefit discussions with recipients. Use of AA donors allows consideration of older donors.

Issue Highlights

Issue Highlights

Rating the Preferences for Potential Harms of Treatments for Cardiovascular Disease

The Institute of Medicine has called for a new health care paradigm that integrates patient values into discussions of the risks and benefits of treatment. Although cardiovascular disease (CVD) affects one-third of Americans, little is known about how adults regard the potential harms or complications of treatment. We sought to determine the preferences of community-dwelling adults for 15 potential harms or complications resulting from treatment of CVD. In a telephone survey, adults older than 18 years residing on Long Island, New York, were asked to score the preferences for 15 potential harms or complications of treatment of CVD on a scale from 0 to 100. All statistical analyses were based on nonparametric methods. Multivariable general linear model analyses were performed to identify demographic factors associated with the score assigned for each adverse outcome. The 807 individuals surveyed generated 723 unique sequences of scores for the 15 outcomes. The ranking of scores from least to most acceptable was stroke, major myocardial infarction (MI), cognitive dysfunction, renal failure, death, prolonged ventilator support, heart failure, angina, sternal wound infection, major bleeding, reoperation, prolonged recovery in a nursing home, cardiac readmission, minor MI, and percutaneous coronary intervention. Demographic factors accounted for less than 7% of the observed variation in the score attributed to each outcome. Individual community-dwelling adults living on Long Island, New York, assign unique values to their preferences for potential harms encountered following treatment of CVD. Thus, risk-benefit discussions and treatment decisions regarding CVD should be harmonized to the value system of each individual.

Lymphoma in Inflammatory Bowel Disease and Treatment Decisions

The risk of lymphoma, particularly non-Hodgkin's lymphoma, is an important concern associated with therapy for inflammatory bowel disease (IBD). Lymphoma risks have been described for nearly all immunomodulatory therapies for IBD, and it is therefore important to have discussions with patients before initiating therapy. However, it is also important to put risks into contexts that IBD patients can appropriately appreciate. Relative risks can appear large for these medications, while, by contrast, the absolute risk may be quite low. Additionally, understanding the risks of foregoing immunomodulatory therapy--specifically, continued active disease and/or continued corticosteroid use--can frame an appropriate risk-benefit discussion for both patients and physicians.

P3-11-02: Changing Paradigms for Breast Cancer Chemoprevention?

Abstract The SERMs tamoxifen and raloxifene are approved for breast cancer risk reduction but their acceptance in clinical practice has been poor largely related to rare but potentially life threatening side effects which requires identification of populations at higher breast cancer risk and careful risk benefit discussion (Visvanathan 2009). Recent findings from randomized placebo-controlled clinical trials suggest potential alternative approaches. In the MAP.3 placebo-controlled trial including 4,650 postmenopausal women, exemestane decreased breast cancer incidence by 65% (P=0.002) (Goss 2011) with no significant difference between groups for fractures, CVD events, other cancers or treatment-related deaths. While the median Gail 5-yr risk score of participants was 2.3, eligibility factors included age alone (≥ 60 years) regardless of calculated breast cancer risk and accounted for 49% of entries. With extended follow-up from the Women's Health Initiative (WHI) randomized, placebo-controlled trial evaluating estrogen alone in 10,739 postmenopausal women with prior hysterectomy, a statistically significant decrease in breast cancer incidence of 23% was seen with estrogen use (P=0.02) (LaCroix 2011). Younger postmenopausal women (age 50–59 years at entry) randomized to estrogen alone had lower risk of myocardial infarction (HR 0.54, 95% CI 0.34−0.86) and death (HR 0.73, 95% CI 0.53−1.00). These findings contrast to those in the WHI trial evaluating combined estrogen plus progestin in 16,608 postmenopausal women with an intact uterus where breast cancers were increased 25% (P=0.004) as was breast cancer mortality (increased by 96%, P=0.049) (Chlebowski 2010). The apparently paradoxical findings that in postmenopausal women estrogen addition, as conjugated equine estrogen, lowers breast cancer incidence and estrogen reduction, by aromatase inhibitor use, also lowers breast cancer incidence are consistent with preclinical studies indicating condition dependent change in estrogen influence on mammary cancers (Jordan 2011). Major eligibility for the WHI trials included anticipated 3-yr survival regardless of breast cancer or CVD risk. The findings from the MAP.3 and WHI trials highlight the complex relationships between estrogen and breast cancer and suggest potential strategies for chronic disease risk reduction in select populations of postmenopausal women which may not require formal breast cancer risk assessment. Visvanathan K, Chlebowski RT, et al. J Clin Oncol 2009;27:3235–3258. Goss PE, Ingle JN, Ales-Martinez J, Cheung A, Chlebowski RT, et al. The NCIC CTG MAP.3 Trial. N Engl J Med 10.1056/NEJMos 1103507. Chlebowski RT, Anderson GL, et al. JAMA 2010;304(15):1684–1692. LaCroix AZ, Chlebowski, RT, et al. JAMA 2011;305(13):1305–14. Jordan VC, Ford LG. Cancer Prev Res. 4:633–7 (2011). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-02.

Monitoring for teratogenic signals: Pregnancy registries and surveillance methods

Pregnant women should have access to medications that have been adequately studied for use to facilitate evidence-based risk-benefit discussions with their health care providers. Pregnant women experience acute medical emergencies, have existing conditions that require continued medical treatment or may develop pregnancy-induced conditions, making drug use during pregnancy unavoidable. Drug labeling is the primary source of information about a drug's use. The safety and efficacy data found in the label is derived from well-controlled clinical trials conducted prior to a drug's approval. However, pregnant women are rarely enrolled in clinical trials unless a product is specifically indicated for a pregnancy-related condition. Consequently, information regarding a product's use during pregnancy is usually collected postapproval. Current data collection tools include pregnancy exposure registries, retrospective cohort studies, pregnancy surveillance programs, case-control studies, spontaneous reports of adverse events and case reports. Each tool has strengths and limitations in its ability to detect teratogenic signals. Combinations of different sources of data are necessary to acquire the most complete picture of potential teratogenic risk, as no single method can capture all desired data to help pregnant patients and women of child bearing potential make appropriate risk benefits decisions along with their health care providers.

Menopausal Hormone Therapy and Subsequent Risk of Specific Invasive Breast Cancer Subtypes in the California Teachers Study

Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype. We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast cancers were diagnosed. Compared with women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT for 15 or more years had an 83% greater risk (95% confidence interval, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m(2) but not for women with BMI of >or=30 kg/m(2). Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2- tumors. Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Furthermore, risks varied by BMI and tumor subtype. These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use.

Human Reproductive Cloning: Science and Jewish Law

Generally speaking, many, although not all Jewish Legal (halachic) authorities oppose human reproductive cloning, (HRC). However, many opinions opposing the practice provide a slew of exceptions, e.g. for momzerim (bastards) or for infertile couples, which dilute the force of the injunction. This paper suggests that current Halachic inquiry is self-limiting, ignoring considerations which would otherwise lead to its outright and absolute ban. Some considerations explored here indicate that HRC is in violation of the divine and natural order, a conclusion in accord with current scientific thinking as constituting a distinct biological threat to the survival of the human species. Under traditional Jewish Law permissibility of human reproductive cloning has been formulated along four lines of inquiry: 1. whether it is permitted as being in furtherance of the Divine Plan (under the rubric of the biblical injunction V’Kivshuha – thou shall shepherd the Earth); 2. whether it is prohibited under the rubric of Kilayim (interbreeding, including prohibiting interference with the Divinely ordered propagation of a species, and preservation of inherent reproductive processes); 3. whether HRC is a mitzva, fulfilling the positive commandment of “Pru U’Rvu,” (i.e to be fruitful and multiply) overiding other concerns (essentially a risk-benefit analysis); and 4. considerations of whether the cloned organism is human, including ramifcations of secular legal obligations and responsibilities. A didactic inquiry into these lines of inquiry is undertaken in this paper, first briefly discussing the basis on which proponents rely and then discussing five separate mega-doctrines under which prohibition would be based: Injunctions against Kilayim (interbreeding), Kishuf (Magic), Requirements of Safeguarding Human Dignity, Respect for the Divine, and Protecting Human Life. Finally, a risk-benefit discussion is undertaken, evaluating risks of human cloning if fails a benefit or utility test, i.e. a determination one cannot rely on cloning to fulfill the obligation to be fruitful and multiply.PART II of this paper undertakes a review of the topic from an exigetical Biblical and Kabbalistic perspective. It is proposed that arguments and the method of analysis discussed raised here may illuminate the inquiry as raised in the secular/legal world.

Menopausal Hormone Therapy, Hormone Receptor Status, and Lung Cancer in Women

Gender differences in lung cancer incidence and outcome suggest a potential role for reproductive hormones. However, observational studies regarding menopausal hormone therapy use and lung cancer have given mixed results. Some have associated hormone therapy use with increased lung cancer risk, while others have shown no effect or found lower lung cancer risk in hormone therapy users. Against this background the Women's Health Initiative (WHI) randomized controlled trial evaluating conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) in postmenopausal women identified an increase in malignancies in the hormone therapy group during the post intervention period. Post hoc analyses identified a statistically significant increase in deaths from lung cancer for women in the hormone group largely related to effects on non-small cell lung cancer (NSCLC). The NSCLCs were more commonly poorly differentiated and were diagnosed at a metastatic stage, suggesting a hormone effect on already established lung cancer growth. Ongoing preclinical and clinical analyses have identified estrogen receptors in the nucleus and cytoplasm of lung tissue and lung cancers. More recently, intriguing associations among estrogen receptor expression, lung cancer histology, clinical prognosis, and epidermal growth factor receptor (EGFR) mutations have been reported. The WHI clinical findings should be integrated into risk-benefit discussion with women considering combined hormone therapy use. In addition, the findings, together with ongoing studies evaluating estrogen receptor status and function, support further efforts to develop lung cancer intervention strategies targeting estrogen receptor expression.

Prophylactic colectomy for hyperplastic polyposis

Hyperplastic polyposis (HP) is important to recognise as it increases the risk of adenomata which may develop dysplastic change or frank adenocarcinoma. We present the case of a 58-year-old woman with HP. Following a diagnosis of HP in this patient, it was noted that the number of polyps were progressively increasing over time, becoming pancolic and extending into the rectum. Genetic testing for a familial polypotic syndrome was negative. Histological analysis demonstrated that the majority of polyps were hyperplastic, but there were also serrated and tubular adenomata with foci of low-grade dysplasia. Whilst there was no evidence of frank malignancy or high-grade dysplasia, following a risk-benefit discussion the patient underwent a laparoscopic total colectomy with an ileal pouch formation. This case highlights the complexity in the management of HP and that even in the absence of confirmed invasive disease, patients may elect to undergo prophylactic colonic resection.

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial

In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period. The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16 608 postmenopausal women aged 50-79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00000611. After a mean of 5.6 years (SD 1.3) of treatment and 2.4 years (0.4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0.16%vs 0.13%; hazard ratio [HR] 1.23, 95% CI 0.92-1.63, p=0.16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0.14%vs 0.11%; HR 1.28, 0.94-1.73, p=0.12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0.11%vs 0.06%; HR 1.71, 1.16-2.52, p=0.01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0.09%vs 0.05%; HR 1.87, 1.22-2.88, p=0.004). Incidence and mortality rates of small-cell lung cancer were similar between groups. Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk-benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer. National Heart, Lung and Blood Institute, National Institutes of Health.

Concerns About Consensus Guidelines for QTc Interval Screening in Methadone Treatment

Concerns About Consensus Guidelines for QTc Interval Screening in Methadone Treatment

Successful Use of Succinylcholine for Cesarean Delivery in a Patient with Postpolio Syndrome

We thank Drs. Connelly and Abbot for their interesting comments on our case report.1They give us the opportunity to clarify the choice our anesthetic strategy in the current case.Drs. Connelly and Abbot mention a number of cases reported in the 1970s in which life-threatening hyperkalemia induced by succinylcholine was observed in patients with denervation pathology. As emphasized in our letter, the use of succinylcholine in patients with postpoliomyelitis syndrome remains controversial because of the risk of fatal hyperkalemia observed in patients with pathology close to postpoliomyelitis syndrome. The molecular mechanism of succinylcholine-induced hyperkalemia has been nicely described by Martyn and Richtsfeld2and results primarily from motor endplate receptor up-regulation. This explains why the expected dangerous increase in serum potassium occurs over a very brief period of time, and why normal preoperative potassium levels have limited value in predicting the magnitude of potassium increase. In our case, preoperative blood potassium was 3.4 mm. Although we did not obtain a postoperative potassium determination, we did not observe any significant electrocardiographic modification, such as T-wave changes indicative of hyperkalemia, in the current case after succinylcholine injection.Drs. Connelly and Abbott also discuss the choice of general versus regional anesthesia in our case. We agree that regional anesthesia has been successfully used in some cases of patients with postpoliomyelitis syndrome. However, we did not consider it as a first-choice strategy because the risk of exacerbating the motor deficit of the limbs due to a toxic action of local anesthetics on the motoneurons could not be excluded. Moreover, there was a lack of symptoms suggesting a diagnosis of postpolio-related central disorder. We disagree with Drs. Connelly and Abbott that the use of a nondepolarizing muscle relaxant for rapid sequence intubation always represents an effective and safe alternative to succinylcholine. None of the nondepolarizing muscle relaxants available to date have the same rapidity of onset and reversal of action as that exhibited by succinylcholine. This particular kinetic profile makes this agent preferable to any other nondepolarizing muscle relaxants to decrease the risk of inhalation of the gastric contents, as was particularly important here for cesarean delivery. We agree that careful titration (dose reduction) and monitoring of succinylcholine effects are necessary, which was performed in our case.Finally, we did not state, as mentioned by Drs. Connelly and Abbot, that succinylcholine should be used in patients with postpoliomyelitis syndrome. From this case, we concluded that the anesthetic strategy must be chosen after an extensive risk–benefit discussion, and that succinylcholine may represent a possible alternative in such patients, pending careful titration and monitoring of its effects.*Beaujon University Hospital, Assistance Publique des Hôpitaux de Paris, Clichy, France. anne.wernet@bjn.aphp.fr