There is a growing consensus that disclosure of medical mistakes is ethically and legally appropriate, but such disclosures are made difficult by medical traditions of concern about medical malpractice suits and by physicians' own emotional reactions. Because the physician may have compelling reasons both to keep the information private and to disclose it to the patient or family, these situations can be conceptualized as privacy dilemmas. These dilemmas may create barriers to effectively addressing the mistake and its consequences. Although a number of interventions exist to address privacy dilemmas that physicians face, current evidence suggests that physicians tend to be slow to adopt the practice of disclosing medical mistakes.This discussion proposes a theoretically based, streamlined, two-step plan that physicians can use as an initial guide for conversations with patients about medical mistakes. The mistake disclosure management plan uses the communication privacy management theory.The steps are 1) physician preparation, such as talking about the physician's emotions and seeking information about the mistake, and 2) use of mistake disclosure strategies that protect the physician-patient relationship. These include the optimal timing, context of disclosure delivery, content of mistake messages, sequencing, and apology. A case study highlighted the disclosure process.This Mistake Disclosure Management Plan may help physicians in the early stages after mistake discovery to prepare for the initial disclosure of a medical mistakes. The next step is testing implementation of the procedures suggested.

Individual patient data meta-analyses using the raw data from primary diagnostic accuracy studies are taking hold in systematic reviews evaluating tests. Conventional reviews and meta-analyses that summarise study-level data on test accuracy (sensitivity and specificity) have several disadvantages. The most fundamental limitation of this approach is that it estimates the rates of test result-given disease (sensitivity is probability of positive test result-given disease is present; and specificity is probability of negative test result-given disease is absent). This may be addressed by summarising predictive values, but estimating accuracy for individual tests without consideration of other tests in the test chains that make up everyday diagnostic work-ups remain a problem. To inform clinical practice it is essential that test evaluation generates information about probability of disease given test results, and that it does so in view of the preceding contribution to diagnosis of other tests, for example, symptoms and signs. A multivariable (logistic regression) framework generates disease probabilities taking into account the important factors that play a role in diagnosis. Most primary accuracy studies lack statistical power to do this, particularly because of the small absolute number of disease events per test included in the diagnostic work. Synthesis using their raw data can overcome this problem, but meta-analysts will have limited success if there are difficulties in obtaining the large majority of valid studies, without 'missing' data on the tests relevant in clinical decision-making. Successful individual patient data meta-analyses create the opportunity to calculate directly and reliably disease probabilities corresponding with realistic chains of tests, thereby making outputs of reviews of test accuracy clinically applicable.

BACKGROUND AND PURPOSE:

The use of standardized outcome measures (OMs) can support clinicians' development of appropriate care plans, guide educators in curricular decisions, and enhance the methodological quality and generalizability of clinical trials. The purposes of this case report are to (1) describe a framework and process for assessing psychometrics and clinical utility of OMs used post-stroke, (2) describe a consensus process used to develop recommendations for stroke-related OMs in clinical practice, research and entry-level physical therapist education, (3) present examples demonstrating how the recommendations have been utilized to date, and (4) make suggestions for future efforts. CASE

DESCRIPTION:

A taskforce of 7 physical therapists with diverse clinical and research expertise in stroke rehabilitation used a 3-stage, modified Delphi consensus process to develop recommendations on OM use. An evidence-based systematic review template and a 4-point rating scheme were used to make recommendations on OM use by care setting and patient acuity, for research, and inclusion in professional education.

OUTCOMES:

An initial list of 77 OMs was developed based on input from numerous professional sources. Screening measures and duplicate measures were eliminated. 56 OMs received full review. Measures spanned the constructs of body structure/function (21), activity (28), and participation (14). Fourteen measures received a rating of "highly recommend".

DISCUSSION:

Use of highly recommended OMs may provide a common set of tools enabling comparisons across patients, interventions, settings, and studies. The use of a clearly defined, comprehensive assessment template may facilitate the pooling of data on OMs and contribute to best practice guidelines. Educational recommendations may inform curricular decisions.

This article presents a systematic review of the recent literature on the scientific support of electromyography (EMG) and nerve conduction velocity (NCV) in diagnosing the exposure and toxicity of organophosphorus pesticides (OP). Specifically, this review focused on changes in EMG, NCV, occurrence of intermediate syndrome (IMS), and OP-induced delayed polyneuropathy (OPIDN) in human. All relevant bibliographic databases were searched for human studies using the key words "OP poisoning", "electromyography", "nerve conduction study," and "muscles disorders". IMS usually occurs after an acute cholinergic crisis, while OPIDN occurs after both acute and chronic exposures. Collection of these studies supports that IMS is a neuromuscular junction disorder and can be recorded upon the onset of respiratory failure. Due to heterogeneity of reports on outcomes of interest such as motor NCV and EMG amplitude in acute cases and inability to achieve precise estimation of effect in chronic cases meta-analysis was not helpful to this review. The OPIDN after both acute and low-level prolonged exposures develops peripheral neuropathy without preceding cholinergic toxicity and the progress of changes in EMG and NCV is parallel with the development of IMS and OPIDN. Persistent inhibition of acetylcholinesterase (AChE) is responsible for muscle weakness, but this is not the only factor involved in the incidence of this weakness in IMS or OPIDN suggestive of AChE assay not useful as an index of nerve and muscle impairment. Although several mechanisms for induction of this neurodegenerative disorder have been proposed as were reviewed for this article, among them oxidative stress and resulting apoptosis can be emphasized. Nevertheless, there is little synchronized evidence on subclinical electrophysiological findings that limit us to reach a strong conclusion on the diagnostic or prognostic use of EMG and NCV for acute and occupational exposures to OPs.

Kaplan-Meier curves and estimates of survival are the most common way to present survival data in medicine, especially for cohorts with different lengths of follow-up. Moreover, Kaplan-Meier curves present a frequently used general graphic approach to display time-to-event outcomes. A solid understanding of how Kaplan-Meier curves are generated and how they should be analyzed and interpreted is of great importance to appraise urological literature in daily clinical practice. This article describes the basic principles of Kaplan-Meier analysis, possible variants and pitfalls. Improved knowledge of Kaplan-Meier analysis can help to improve Evidence-based urology and its application in patient care.

BACKGROUND:

In this era of escalating health care costs and the questionable effectiveness of multiple interventions, cost effectiveness or cost utility analysis has become the cornerstone of evidence-based medicine, and has an influence coverage decisions. Even though multiple cost effectiveness analysis studies have been performed over the years, extensive literature is lacking for interventional techniques. Cost utility analysis studies of epidural injections for managing chronic low back pain demonstrated highly variable results including a lack of cost utility in randomized trials and contrasting results in observational studies. There has not been any cost utility analysis studies of epidural injections in large randomized trials performed in interventional pain management settings.

OBJECTIVES:

To assess the cost utility of caudal epidural injections in managing chronic low back pain secondary to lumbar disc herniation, axial or discogenic low back pain, lumbar central spinal stenosis, and lumbar post surgery syndrome.

STUDY DESIGN:

This analysis is based on 4 previously published randomized trials.

SETTING:

A private, specialty referral interventional pain management center in the United States.

METHODS:

Four randomized trials were conducted assessing the clinical effectiveness of caudal epidural injections with or without steroids for lumbar disc herniation, lumbar discogenic or axial low back pain, lumbar central spinal stenosis, and post surgery syndrome. A cost utility analysis was performed with direct payment data for a total of 480 patients over a period of 2 years from these 4 trials. Outcome included various measures with significant improvement defined as at least a 50% improvement in pain reduction and disability status.

RESULTS:

The results of 4 randomized controlled trials of low back pain with 480 patients with a 2 year follow-up with the actual reimbursement data showed cost utility for one year of quality-adjusted life year (QALY) of $2,206 for disc herniation, $2,136 for axial or discogenic pain without disc herniation, $2,155 for central spinal stenosis, and $2,191 for post surgery syndrome. All patients showed significant improvement clinically and showed positive results in the cost utility analysis with an average cost per one year QALY of $2,172.50 for all patients and $1,966.03 for patients judged to be successful. The results of this assessment show a better cost utility or lower cost of managing chronic, intractable low back pain with caudal epidural injections at a QALY that is similar or lower in price than medical therapy only, physical therapy, manipulation, and surgery in most cases.

LIMITATIONS:

The limitations of this cost utility analysis include that it is a single center evaluation, even though 480 patients were included in the analysis. Further, only the costs of interventional procedures and physician visits were included. The benefits of returning to work were not assessed.

CONCLUSION:

  This cost utility analysis of caudal epidural injections in the treatment of disc herniation, axial or discogenic low back pain, central spinal stenosis, and post surgery syndrome in the lumbar spine shows the clinical effectiveness and cost utility of these injections at less than $2,200 per one year of QALY.

Previous kinetic investigations of the N-terminal RNA Recognition Motif (RRM) domain of spliceosomal A protein of the U1 small nuclear ribonucleoprotein particle (U1A) interacting with its RNA target U1 hairpin II (U1hpII) provided experimental evidence for a 'lure and lock' model of binding. The final step of locking has been proposed to involve conformational changes in an α-helix immediately C-terminal to the RRM domain (helix C), which occludes the RNA binding surface in the unbound protein. Helix C must shift its position to accommodate RNA binding in the RNA-protein complex. This results in a new hydrophobic core, an intraprotein hydrogen bond and a quadruple stacking interaction between U1A and U1hpII. Here, we used a surface plasmon resonance-based biosensor to gain mechanistic insight into the role of helix C in mediating the interaction with U1hpII. Truncation, removal or disruption of the helix exposes the RNA-binding surface, resulting in an increase in the association rate, while simultaneously reducing the ability of the complex to lock, reflected in a loss of complex stability. Disruption of the quadruple stacking interaction has minor kinetic effects when compared with removal of the intraprotein hydrogen bonds. These data provide new insights into the mechanism whereby sequences C-terminal to an RRM can influence RNA binding.

Clinical practice guidelines (CPGs) have become increasingly important in recent years due to an increasing emphasis on evidence-based practice, as well as serious discussions in academic, medical, and legal circles about their possible role in measuring physician performance, setting provider reimbursement strategy, and establishing protection from litigation in the future. At the same time, CPGs are costly to develop. Thus, as CPGs gain influence in medical practice, it will become essential that CPGs are developed using trustworthy standards and that the authors of CPGs are not being unduly influenced by financial pressures from external stakeholders. Since 2004, the 9 CPGs sponsored by the American Academy of Otolaryngology-Head and Neck Surgery Foundation have been developed with full disclosure and appropriate management of potential financial conflicts of interest. This commentary discusses the potential for conflict of interest in otolaryngology CPGs and how the otolaryngology guideline development process can serve as a model for other professional medical organizations.

Resection of cholangiocarcinoma often results in a positive ductal margin, from carcinoma in situ (CIS) near the main tumor; however, the biological behavior of the residual CIS after surgical resection remains equivocal. We report a case of late local recurrence of CIS, defined as long-term tumor progression from CIS residue at the ductal stump. The patient, a 73-year-old man, had undergone bile duct resection for distal cholangiocarcinoma, leaving positive ductal margins with CIS. A biliary stricture was found 10 years later at the site of anastomosis, and right hepatectomy with pancreatoduodenectomy was performed. Based on histological analogy and the evidence of remnant CIS, a final diagnosis of late local recurrence from the CIS foci was made. This uncommon mode of recurrence should be considered in patients with early-stage disease with expected favorable survival because salvage surgery is feasible for selected patients.

Chronic inflammation may be important in endometrial cancer etiology. Several established endometrial cancer risk factors, particularly obesity, are hypothesized to operate through this pathway by increasing proinflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and acute-phase protein C-reactive protein (CRP). This study sought to investigate the association between inflammatory markers and the risk of endometrial cancer (types I and II). We recruited 519 incident endometrial cancer cases and 964 frequency age-matched controls in this population-based case-control study in Alberta (Canada) from 2002 to 2006. Participants completed in-person interviews, were assessed for anthropometric measures, and provided 8-h fasting blood samples either preoperatively or postoperatively. Blood was analyzed for the concentrations of TNF-α, IL-6, and CRP by immunoassay. Endometrial cancer cases had consistently higher mean levels of TNF-α, IL-6, and CRP compared with controls in these predominantly postmenopausal women. After adjusting for age, all markers were associated with statistically significant increased risks for endometrial cancer; however, after multivariable adjustment, only the risk from CRP remained elevated (odds ratio=1.22, 95% confidence interval: 1.02-1.47). Similarly, upon stratification by cancer type, only CRP was associated positively with an increased risk for type I endometrial cancer (odds ratio=1.25, 95% confidence interval: 1.03-1.52). All markers were associated with an elevated risk for the more rare and aggressive type II cancers; however, these findings were statistically nonsignificant, likely because of the small number of cases in this group. In conclusion, we found epidemiologic evidence for an association between CRP and the risk of endometrial cancer, which was slightly stronger for type I cancer. No associations emerged for TNF-α and IL-6.