Resective epilepsy surgery: assessment of randomized controlled trials

Neurosurgical Review - Epilepsy is the most common form of chronic neurologic disease. Here, we review the available randomized controlled trials (RCTs) that examined the efficacy of resective...     

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BackgroundFew studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival.MethodsWe queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival.Results2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46–2.31], reference R0).ConclusionsPositive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.     

The importance of the margin of resection and external radiation in non-lipomatous retroperitoneal sarcoma

BackgroundPrior studies evaluating the impact of adjuvant or neoadjuvant radiation on clinical outcomes of patients with non-lipomatous retroperitoneal sarcoma have been underpowered.MethodsWe queried the National Cancer Database to identify patients undergoing surgical resection of retroperitoneal sarcoma with non-lipomatous histology from 2004 to 2016. Multivariable logistic regression and Cox proportional hazards modelling with patients stratified by tumor size were used to identify factors associated with overall survival.Results3,394 patients met inclusion criteria. 592 had small (<5 cm), 1,186 had intermediate (5–10 cm), and 1,616 had large (>10 cm) tumors. Use of either neoadjuvant or adjuvant radiotherapy was associated with improved survival for patients with intermediate (neoadjuvant HR 0.67, CI [0.46, 0.98]; adjuvant HR 0.61, CI [0.50, 0.76]) and large (neoadjuvant HR 0.50, CI [0.37, 0.68]; adjuvant HR 0.56, CI [0.47, 0.69]) tumors, while adjuvant radiation therapy was associated with a survival benefit for small-sized tumors (HR 0.67, CI [0.46, 0.99]).ConclusionsRadiation therapy is associated with an overall survival benefit in patients presenting undergoing resection of non-lipomatous retroperitoneal sarcoma.     

Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis

Background Antimicrobial susceptibility testing (AST) of bacterial isolates is a time- and resource-intensive procedure recommended by cystic fibrosis (CF) treatment guidelines for antimicrobial selection for pulmonary exacerbation (PEx) treatment.Methods We studied relationships between Pseudomonas aeruginosa (Pa) isolate AST results, antipseudomonal PEx treatments, and treatment responses as change in weight and percent predicted forced expiratory volume in 1 s (ppFEV₁) as well as future antimicrobial treatment hazard for PEx occurring at a CF care center from 1999 through 2018. Treatments were categorized by “Pa coverage” as complete (all Pa isolates susceptible by AST to at least one administered agent), none (no isolates susceptible), incomplete (some, but not all isolates susceptible), and indeterminant (administered antipseudomonals not evaluated by AST). Weight and ppFEV₁ responses were compared across Pa coverage categories using unadjusted and adjusted general estimating equations; hazard of future treatment was assessed by Cox and logistic regression.Results Among 3820 antimicrobial PEx treatment events in 413 patients with Pa, 62.6% (2390) had complete Pa coverage; 8.9% (340), 2.4% (99), and 26.2% (1000), had no, incomplete, and indeterminant Pa coverage, respectively. Mean baseline to follow-up weight change was +0.74 kg [95% CI 0.63, 0.86]; ppFEV₁ change was +1.60 [1.29, 1.90]. Pa coverage category was not associated with significant differences in weight or ppFEV₁ change or with future antimicrobial treatment hazard.Conclusions We did not observe superior responses for AST-defined complete Pa coverage treatments versus lesser coverage treatments, suggesting that AST may be of little utility in choosing antimicrobials for CF PEx treatment.     

Female Genital Cutting and Deinfibulation: Applying the Theory of Planned Behavior to Research and Practice

At least 200 million girls and women across the world have experienced female genital cutting (FGC). International migration has grown substantially in recent decades, leading to a need for health care providers in regions of the world that do not practice FGC to become knowledgeable and skilled in their care of women who have undergone the procedure. There are four commonly recognized types of FGC (Types I, II, III, and IV). To adhere to recommendations advanced by the World Health Organization (WHO) and numerous professional organizations, providers should discuss and offer deinfibulation to female patients who have undergone infibulation (Type III FGC), particularly before intercourse and childbirth. Infibulation involves narrowing the vaginal orifice through cutting and appositioning the labia minora and/or labia majora, and creating a covering seal over the vagina with appositioned tissue. The WHO has published a handbook for health care providers that includes guidance in counseling patients about deinfibulation and performing the procedure. Providers may benefit from additional guidance in how to discuss FGC and deinfibulation in a manner that is sensitive to each patient’s culture, community, and values. Little research is available to describe decision-making about deinfibulation among women. This article introduces a theoretically informed conceptual model to guide future research and clinical conversations about FGC and deinfibulation with women who have undergone FGC, as well as their partners and families. This conceptual model, based on the Theory of Planned Behavior, may facilitate conversations that lead to shared decision-making between providers and patients.

     

A comparison of the effect of estrogen with or without progesterone on mood and physical symptoms in postmenopausal women

Using a randomized, placebo-controlled design, this study assessed the effects of estrogen alone (ES) or in combination with cyclic progesterone (EP) on daily ratings of mood and physical symptoms before and after 6 months of daily hormone treatment. Fifty-four postmenopausal women were recruited from the community at large and specifically selected as being asymptomatic at the time of enrollment and without significant psychiatric history. Ratings were obtained every day for 30 days prior to treatment and again every day during the last 30 days of treatment. Results revealed that when compared with pretreatment levels, women randomized to EP (n = 16) exhibited statistically significant increases in daily depression, cramping, and breast tenderness and a marginally significant increase in daily anxiety. However, these increases were mild, not clinically significant, and did not interfere with normal functioning. Women randomized to ES (n = 20) showed no significant change in daily mood measures, although they did experience an increase in breast tenderness with estrogen. A significant placebo (n = 18) effect was observed, as there was a reliable reduction in daily irritability ratings (p < 0.05) with placebo. These findings suggest that for most postmenopausal women, the use of hormones will not be associated with clinically significant changes in mood or physical symptoms, which weighs favorably into the cost-benefit ratio for women considering hormone replacement therapy.     

Midazolam-induced retrieval impairments revealed by the use of flumazenil: a study in surgical dental patients

Twenty-one outpatients attending Guy's Dental Hospital received intravenous midazolam prior to the removal of at least one wisdom tooth. The patient's memory for material presented both before and after midazolam was assessed either whilst still in the drug-treated condition (midazolam+placebo) or in the drug-reversed condition (midazolam+flumazenil). There were no differences between the two retrieval conditions in the number of words or pictures correctly recalled or recognized and both groups showed significantly better memory for material presented prior to midazolam administration. In a word completion task both groups showed a significant and equal priming effect, in that they completed more words with those to which they had been previously exposed in a rating task. However, the groups differed significantly in the total number of words correctly completed, with the drug-reversed group completing more. The word completion task is a problem- solving task requiring retrieval from semantic memory. There was further evidence that midazolam might impair retrieval from semantic memory from the number of subjects making spelling errors; this was significantly greater in the midazolam group than in the midazolam+flumazenil group. Finally, free recall of the dental procedures was significantly different in the two retrieval conditions. The midazolam+flumazenil group remembered significantly more items, and this effect was particularly marked for patients who had all four wisdom teeth removed. Flumazenil significantly reversed the midazolam-induced decrease in tapping rate (an objective measure of sedation), significantly attenuated the reduction in self-rated anxiety and significantly increased shaking and trembling.     

Time course and predictors of symptoms after primary prostate cancer therapy.

PURPOSE: Understanding the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer (PC) may improve patients' choice of treatment and later help them adjust to its consequences. We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies. PATIENTS AND METHODS: In a prospective cohort study of 417 men we assessed urinary, bowel, and sexual function from before primary treatment to 24 months after. To control for potential confounding, we measured sociodemographic and PC prognostic factors, medical comorbidity, and pretreatment function commonly affected by PC and its treatment. RESULTS: Patients who underwent external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT) differed significantly in sociodemographic factors, cancer prognostic factors, and pretreatment symptom status, especially sexual function. Urinary incontinence increased sharply after RP, while bowel problems and urinary irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in all patients, particularly after radical prostatectomy, and nerve-sparing surgical technique had little apparent benefit. There was no change in urinary function and little change in overall bowel function after 12 months, but the time course of sexual dysfunction varied by treatment and, for bowel function, by symptom. Multiple regression modeling confirmed that treatment influences all 24-month outcomes, but residual confounding persisted. CONCLUSION: Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction. With this information, patients and their physicians may refine their choice of treatment and better anticipate its consequences.     

Assessing the need to update prevention guidelines: a comparison of two methods.

BACKGROUND: An important concern for developers of clinical practice guidelines is how best to determine when guidelines require updating to ensure they remain current and evidence based. Because of the high costs associated with updating guidelines, recent attention has focused on approaches that can reliably assess the extent of updating required. Recently, Shekelle and colleagues proposed a model of limited literature searches with modest expert involvement as a way to reduce the cost and time requirements for assessing whether a guideline needs updating. METHODS: The main objective of this study was to compare the Shekelle et al. assessment model (review approach) and a conventional process using typical systematic review methods (traditional approach) in terms of comprehensiveness and effort. We modeled the review approach on that by Shekelle and colleagues but refined it iteratively over three phases to achieve greater efficiency. Using both methods independently, we assessed the need to update six topics from the 1996 Guide to Clinical Preventive Services from the US Preventive Services Task Force. Main outcomes included completeness of study identification, importance of missed studies and the effort involved. RESULTS: Although the review approach identified fewer eligible studies than the traditional approach, none of the studies missed was rated as important by task force members acting as liaisons to the project with respect to whether the topic required an update. On average, the review approach produced substantially fewer citations to review than the traditional approach. The effort involved and potential time saving depended largely on the scope of the topic. CONCLUSIONS: The revised review approach provides an efficient and acceptable method for judging whether a guideline requires updating.     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.