Large colonic neoplasms missed by endoscopy

Endoscopy is commonly accepted as the gold standard in the evaluation of neoplastic colonic disease. The procedure is used to confirm or exclude lesions detected on barium enemas, with the assumption that the endoscopist was successful in reaching the appropriate segment of the colon. We collected 18 cases, all with proved colonic neoplasm 2-8 cm in diameter that were detected by barium enema but overlooked on initial endoscopy. All of the lesions were relatively flat with little intraluminal protuberance. Histologic examination showed malignant foci in six of 11 tumors that were resected. In two of the other seven patients, unresected lesions progressed to advanced carcinomas. This experience suggests that a repeat barium enema is indicated when endoscopy fails to detect a colonic tumor suspected on barium enema examination.     

A prospective trial of colchicine for primary biliary cirrhosis

We entered 60 patients with primary biliary cirrhosis in a double-blind randomized controlled trial to determine whether colchicine is therapeutically effective. Thirty patients had early disease (Stages 1 and 2), and 30 had advanced disease (Stages 3 and 4). Fifteen patients with early disease and 15 with advanced disease received colchicine (0.6 mg twice daily), and the remainder received placebo. Patients were studied about every two months; those remaining in the blind phase at two years underwent repeat liver biopsy and were then placed on open-label colchicine (0.6 mg twice daily). With a few exceptions, the results in patients with early disease were similar to those in patients with advanced disease; hence, data on patients in all stages were combined in the main analysis. During the two-year study period the colchicine-treated patients, as compared with the placebo-treated patients, had improvement in levels of serum albumin, serum bilirubin, alkaline phosphatase, cholesterol, and aminotransferases. However, there was no such improvement in the severity of symptoms or physical findings; moreover, there was no significant difference in the histologic changes noted at liver biopsy in the two treatment groups. At four years after entry, the cumulative mortality from liver disease was 21 percent in patients given colchicine and 47 percent in those given placebo (P = 0.05). The only side effect of colchicine was diarrhea, noted in three patients. The consistent and significant improvement in a number of markers of liver disease and the apparent decreased mortality from liver disease suggest that colchicine may provide some long-term clinical benefit in patients with primary biliary cirrhosis. However, the failure of colchicine to reduce hepatic inflammation and fibrosis leaves uncertain the effect of the drug on the longterm outcome of this disease.     

Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode

BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.     

Inter-rater reliability of surgical reviews for AREN03B2: A COG renal tumor committee study

Purpose

The Children's Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology, pathology, and the surgical procedure to determine appropriate risk-based therapy. The purpose of this study was to determine the inter-rater reliability of the surgical reviews.

Methods

Of the first 3200 enrolled AREN03B2 patients, a sample of 100 enriched for blood vessel involvement, spill, rupture, and lymph node involvement was selected for analysis. The surgical assessment was then performed independently by two blinded surgical reviewers and compared to the original assessment, which had been completed by another of the committee surgeons. Variables assessed included surgeon-determined local tumor stage, overall disease stage, type of renal procedure performed, presence of tumor rupture, occurrence of intraoperative tumor spill, blood vessel involvement, presence of peritoneal implants, and interpretation of residual disease. Inter-rater reliability was measured using the Fleiss' Kappa statistic two-sided hypothesis tests (Kappa, p-value).

Results

Local tumor stage correlated in all 3 reviews except in one case (Kappa = 0.9775, p < 0.001). Similarly, overall disease stage had excellent correlation (0.9422, p < 0.001). There was strong correlation for type of renal procedure (0.8357, p < 0.001), presence of tumor rupture (0.6858, p < 0.001), intraoperative tumor spill (0.6493, p < 0.001), and blood vessel involvement (0.6470, p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753, p < 0.001) and interpretation of residual disease status (0.5310, p < 0.001).

Conclusion

The inter-rater reliability of the surgical review is high based on the great consistency in the 3 independent review results. This analysis provides validation and establishes precedent for real-time central surgical review to determine treatment assignment in a risk-based stratagem for multimodal cancer therapy.     

Can spinal surgery in England be saved from litigation: a review of 978 clinical negligence claims against the NHS

Purpose

The aim of this study is to evaluate the true incidence of all clinical negligence claims against spinal surgery performed by orthopaedic spinal surgeons and neurosurgeons in the National Health Service (NHS) in England, including both open and closed claims.

Methods

This study was a retrospective review of 978 clinical negligence claims held by NHS Resolution against spinal surgery cases identified from claims against ‘Neurosurgery’ and ‘Orthopaedic Surgery’. This category included all emergency, trauma and elective work and all open and closed cases without exclusion between April 2012 and April 2017.

Results

Clinical negligence claims in spinal surgery were estimated to cost £535.5 million over this five-year period. There is a trend of both increasing volume and estimated costs of claims. The most common causes for claims were ‘judgement/timing’ (512 claims, 52.35%), ‘interpretation of results/clinical picture’ (255 claims, 26.07%), ‘unsatisfactory outcome to surgery’ (192 claims, 19.63%), ‘fail to warn/informed consent’ (80 claims, 8.13%) and ‘never events’ including ‘wrong site surgery’ or ‘retained instrument post-operation’ (26 claims, 2.66%). A sub-analysis of 3 years including 574 claims revealed the most prevalent pathologies were iatrogenic nerve damage (132 claims, 23.00%), cauda equina syndrome (CES) (131 claims, 22.82%), inadequate decompression (91 claims, 15.85%), iatrogenic cord damage (72 claims, 12.54%), and infection (51 claims, 8.89%).

Conclusions

The volume and costs of clinical negligence claims is threatening the future of spinal surgery. If spinal surgery is to continue to serve the patients who need it, most thorough investigation, implementation and sharing of lessons learned from litigation claims must be systematically carried out.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

Open image in new window

     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

First episode schizophrenia-related psychosis and substance use disorders: acute response to olanzapine and haloperidol

BACKGROUND: Co-occurring substance use disorders, mostly involving alcohol, cannabis or cocaine, occur commonly in patients with schizophrenia and are associated with increased morbidity and mortality. Available but limited data suggest that substance use disorders (especially cannabis use disorders) may also be common in first-episode patients and appear linked to a poor outcome in these patients. Strategies to curtail substance use form an important dimension of the treatment program for both first-episode and chronic patients. We report on rates of co-occurring substance use disorders in patients within their first episode of schizophrenia-related psychosis from a multicenter, international treatment trial of olanzapine vs. haloperidol. METHODS: The study involved 262 patients (of 263 who were randomized and who returned for a post-randomization evaluation) within their first episode of psychosis (schizophrenia, schizoaffective disorder or schizophreniform disorder) recruited from 14 academic medical centers in North America and Western Europe. Patients with a history of substance dependence within 1 month prior to entry were excluded. RESULTS: Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder (SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had a lifetime diagnosis of alcohol use disorder (AUD). Patients with SUD were more likely to be men. Those with CUD had a lower age of onset than those without. Patients with SUD had more positive symptoms and fewer negative symptoms than those without SUD, and they had a longer duration of untreated psychosis. The 12-week response data indicated that 27% of patients with SUD were responders compared to 35% of those without SUD. Patients with AUD were less likely to respond to olanzapine than those without AUD. DISCUSSION: These data suggest that first-episode patients are quite likely to have comorbid substance use disorders, and that the presence of these disorders may negatively influence response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12 weeks of treatment.     

Psychometric Assessment of the Brazilian Version of the Breastfeeding Self-Efficacy Scale

ABSTRACT Objectives: The purpose of this study was to translate and psychometrically assess the Breastfeeding Self-Efficacy Scale (BSES) among women living in Fortaleza, CE, Brazil, and examine the relationship between breastfeeding self-efficacy (BSE) and maternal demographic variables.
Design and Sample: This methodological study is the first translation of BSES conducted in South America. The psychometric assessment of the original study was replicated. This methodological study enrolled a group (sample of judgment) of 117 pregnant women.
Measures: BSES and maternal sociodemographic variables were studied.
Results: The Cronbach's α coefficient for the translated BSES was .88. Significant differences in BSES scores were found among mothers with a previous satisfactory breastfeeding experience ( M =145.81; SD =±6.82, p =.0001). Significant relationships were found among prenatal BSE and maternal age ( r =.228; p =.01), educational level ( r =.234; p =.01), and marital status ( r =.183; p =.04). No relationship was found among BSE and maternal occupation, family income, or number of pregnancies.
Conclusions: Altogether, our findings suggest that BSES translated into Portuguese may be a reliable and valid measure to assess maternal BSE in Brazilian culture. Minor changes may be needed to use it in other Portuguese-speaking countries, such as Portugal and Mozambique.