Free radicals and antioxidant therapy in clinical practice: to be or not to be?

Free radicals and antioxidant therapy have attracted a great deal of attention in recent years. Current research reveals the potential applications of antioxidants in prevention or control of disease. However, controversy still exists due to lack of well controlled clinical trials and definitive conclusion on efficacy/safety. This article highlights the debatable issues related to this. Based on the available literature and clinician's experience, recommendation on antioxidant usage is mentioned at the end. There is a need to assimilate the known available information with extensive research to establish a positive role of antioxidant therapy in clinical practice and to use an evidence-based approach for summarizing data, drawing conclusions and making recommendations about antioxidant usage and efficacy. A substantial gap still exists between the claims and the efficacy/safety in this area of research.     

Blogs and Twitter in medical publications: too unreliable to quote, or a change waiting to happen?

With the ubiquitous connectivity offered by the Internet, social media sites (like Twitter and Facebook) and personal publishing platforms (blogs) are proliferating rapidly. In this new, evolving scenario of social media, these tools become an important medium to disseminate information at a lightning speed. However, the conventional medical publication model is less than eager to regard them as equivalent to traditional modes of information dissemination. In this article we examine the role played by social media as a critic of the medical publication system, and how it acts as a safeguard by building a platform for post-publication peer review.     

Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guérin

ObjectivesEvaluate the efficacy and safety of valrubicin for bacillus Calmette-Guérin (BCG)–refractory carcinoma in situ (CIS) of the bladder based on updated phase III pivotal trial efficacy data together with efficacy and safety data from a supportive phase II/III study.Materials and MethodsIn a phase II/III open-label study (A9303), BCG refractory/intolerant adults with CIS (≥1 previous course of BCG or could not complete a BCG course owing to toxicity or contraindication) were randomized to receive 6 or 9 weekly intravesical valrubicin (800 mg) instillations. In the pivotal phase III open-label study, BCG-refractory/recurrent adults with CIS (≥2 previous courses of intravesical therapy, including ≥1 BCG course) received 6 weekly intravesical valrubicin (800 mg) instillations. Patients with muscle-invasive disease were excluded. Patients underwent a primary disease evaluation (PDE) at 3 months (～6 weeks after last dose) that included cytoscopy, biopsy, and cytology. Disease recurrence was monitored at 3-month intervals. Complete response (CR) was defined as no evidence of disease at the PDE (month 3) and follow-up (month 6). Efficacy data from the pivotal trial reflect updated information based on US Food and Drug Administration review. Safety assessments in A9303 included local bladder adverse events (LBAEs) and other adverse events (AEs).ResultsEighty patients enrolled and 78 completed treatment and underwent the PDE in study A9303; in the pivotal trial, the respective numbers were 90 and 87 patients. In study A9303, 39% of patients had received ≥2 previous courses of BCG and 11% had received ≥3 courses vs. 70% and 28%, respectively, in the pivotal trial. In both studies, the CR rate was 18%. In A9303, LBAEs were the most common AEs, reported by 86% of patients during treatment and 45% during follow-up; most treatment-related LBAEs were mild to moderate. 2 serious AEs in 1 patient (azotemia/reflux nephropathy) were judged as definitely or possibly treatment related; none of the patient deaths were judged to be related to valrubicin.ConclusionsTwo trials of valrubicin in patients with CIS demonstrate a consistent degree of efficacy in highly pretreated patients (pivotal trial; BCG-refractory patients) and those with fewer previous therapies (A9303; BCG-refractory/intolerant patients).     

Evolution or revolution? Adapting to complexity in wound management

Wound clinics are seeing an increase in the number of 'complex' wounds, which arise as the result of the interaction between multiple coexisting systemic pathologies, environmental factors and local wound factors. These complex wounds require an approach to diagnosis and management that can encapsulate all these factors. Unified wound assessment approaches such as HEIDI (History, Examination, Investigations, Diagnosis and management plan), wound bed preparation and applied wound management systems are essential to reach a definitive diagnosis and to ensure that management is agreed between the various clinical specialities that may be involved. A series of case histories is presented that illustrate the benefits of a unified approach to wound management. Results of a study into the cost-effectiveness of an improved foam dressing are presented, and the problems of demonstrating the ability to make long-term savings through short-term expenditure are discussed.     

Cyclic supraventricular tachycardia in the parturient: to treat or not to treat?

Cardiac arrhythmias are more common in pregnant women than in non-pregnant women. In the asymptomatic pregnant patient with a stable fetus, watchful waiting might be the best strategy. Herein, we describe the first reported case of a pregnant patient who developed cyclic supraventricular tachycardia during labor. No treatment was prescribed, with a good maternal and fetal outcome.     

Acute Symptomatic Seizures and Provoked Seizures: to Treat or Not to Treat?

Purpose of review

Acute symptomatic and provoked seizures by definition occur in close proximity to an event and are considered to be situational. The treatment implications and likelihood of recurrence of acute symptomatic and provoked seizures differ from unprovoked seizures. In this article, the authors review the literature on acute symptomatic and provoked seizures with regard to therapeutic approach and risk of recurrence.

Recent findings

In the acute period, patients who suffer from acute symptomatic and provoked seizures have higher rates of morbidity and mortality. Patients with acute symptomatic seizures in the setting of certain conditions including subdural hemorrhage, traumatic penetrating injuries, cortical strokes, neurocysticercosis, venous sinus thrombosis, and viral encephalitis have a higher rate of seizure recurrence although the rate of recurrence of seizures is less than that of patients with unprovoked seizures.

Summary

In patients with acute symptomatic and provoked seizures, short-term treatment with anti-seizure medications is appropriate given the higher morbidity and mortality in the acute phase of illness. In patients with acute symptomatic seizures with persistent epileptiform activity on EEG and structural changes on imaging, longer-term treatment (i.e., a few months as opposed to 1 week) with anti-seizure medications can be considered due to high risk of seizure recurrence. If a patient subsequently has an unprovoked seizure, there is yet a higher risk of recurrence of seizures and likelihood of the development of epilepsy. In these patients, long-term seizure treatment can be considered, keeping in mind that although anti-seizure treatment may reduce risk of seizure recurrence in the short-term, it does not appear to influence long-term seizure remission rates.

     

Proteinuria in diabetes: bystander or pathway to cardiorenal disease?

The development of albuminuria in diabetics is closely associated with an enhanced risk of renal and cardiovascular disease. However, the role of albuminuria in the pathogenesis of these clinical conditions remains controversial. Whether albuminuria is simply a biomarker or qualifies as a surrogate endpoint for cardiorenal disease has wide-ranging implications from the monitoring and treatment of patients to the design of clinical trials and drug development. We critically review available data to determine whether the association between albuminuria and cardiorenal disease is causative. Current evidence suggests the significance of albuminuria depends on its severity (degree or level) and on the specific clinical outcome under consideration. For diabetic kidney disease, there is convincing epidemiologic and experimental evidence to assign clinical albuminuria status as a surrogate endpoint, but for lower levels of albuminuria (microalbuminuria and normoalbuminuria), the evidence is inconclusive or not available. Albuminuria of any degree is unlikely to be causally related to diabetic cardiovascular disease, but its onset might be useful to identify those subjects at cardiovascular risk and to detect and treat other modifiable risk factors.     

Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?

Large core needle biopsies using stereotactic mammography or ultrasound guidance are now commonly performed as the initial diagnostic approach to nonpalpable breast lesions. Although the subsequent management of patients with invasive cancer, ductal carcinoma in situ, and most benign lesions diagnosed on core needle biopsy specimens is straightforward, certain nonmalignant lesions pose dilemmas with regard to the most appropriate clinical management following core needle biopsy. The purpose of this article is to review the available data regarding several nonmalignant breast lesions, which when encountered in core needle biopsy specimens raise repeated management questions. These include atypical ductal hyperplasia, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), papillary lesions, radial scars, fibroepithelial lesions, mucocele-like lesions, and columnar cell lesions.     

Which to Use to Evaluate Change in BMD at Follow-Up: RMS-SD or RMS-%CV?

There is bias toward the use of root-mean-square standard deviation (RMS-SD) over root-mean-square coefficient of variation (RMS-%CV) to calculate a least significant change (LSC) value that is used to determine if change in bone mineral density (BMD) at follow-up is statistically significant. In part, this bias is based on the assumption that SD is relatively constant over a wide range of BMD as opposed to %CV, which is assumed to increase as BMD decreases. However, evidence to support these assumptions is scant. The purpose of this project was to determine the frequency of discrepancies in interpretation of follow-up data using an LSC based on RMS-SD (LSC-SD) vs RMS-%CV (LSC-%CV). A convenience sample of 100 patients returning for follow-up dual-energy X-ray absorptiometry scans was used to compare the frequency of change in BMD exceeding LSC-SD vs LSC-%CV. Results showed that agreement in exceeding (or not) both LSC-SD and LSC-%CV was 94% for L1-L4 (lumbar spine), femoral neck, and total hip. Disagreements were characterized by BMD changes that usually marginally exceeded either LSC-SD or LSC-%CV but not the other, and they occurred at both high and low absolute BMD. We conclude that significant change in BMD typically exceeds both LSC-SD and LSC-%CV. Thus, there seems to be no basis for the bias in favor of using LSC-SD as long as RMS-SD and RMS-%CV are calculated in the same manner. Furthermore, a criterion that both LSC-SD and LSC-%CV must be exceeded may help avoid overcalling marginal change as being significant, especially at high and low BMD.     

Misattributed paternity in a living related donor: to disclose or not to disclose?

Many ethical considerations surround living kidney donation, some of which are not anticipated. We present a case in which misattributed paternity was inadvertently discovered during the workup of a father and son and present arguments for and against disclosure of this information. We recommend that transplant programs advise patients participating in living organ donor programs that misattributed paternity might be discovered during routine preoperative testing and that protocols for dealing with complex ethical issues be in place.     

Is a flexible mitral annuloplasty ring superior to a semi-rigid or rigid ring in terms of improvement in symptoms and survival?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether, in patients with mitral regurgitation secondary to degenerative mitral valve disease requiring mitral valve repair with an annuloplasty ring, a flexible ring is superior to a semi-rigid or rigid ring in terms of improvement in symptoms and survival. Using the reported search 478 papers were identified. Twelve papers of which seven were echocardiographic studies and five clinical studies, including two randomised controlled trials (RCTs), represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated for these. We conclude that current best available evidence suggests that, in patients with a flexible annuloplasty ring compared to patients with a semi-rigid/rigid annuloplasty ring, the improvement in LV systolic function as reported by all the seven sophisticated echocardiographic studies with a total of 266 patients does not translate into better clinical outcomes as five clinical studies with a total of 941 patients, including two RCTs, report comparable clinical outcomes for patients with mitral regurgitation secondary to degenerative mitral valve disease requiring mitral valve repair with an annuloplasty ring.