Is Bevacizumab (Avastin) Safe and Effective as Adjuvant Chemotherapy for Adult Patients With Stage IIIb or IV Non-Small Cell Lung Carcinoma (NSCLC)?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not bevacizumab (avastin) is safe and effective as adjuvant chemotherapy for adult patients with stage IIIb or IV non-small cell lung carcinoma (NSCLC). STUDY DESIGN: Review of three randomized controlled trials (RCT) published in 2006, 2009, and 2011, all English language. DATA SOURCES: Two randomized, double-blind, controlled clinical trials comparing bevacizumab to placebo as adjunctive chemotherapy, and one RCT comparing bevacizumab as adjunctive chemotherapy versus the use of no adjunctive chemotherapy. All articles were found using PubMed, Medline, and OVID. OUTCOMES MEASURED: Overall survival (OS) and progression-free survival (PFS) were measured. OS was defined as time from randomization to death from any cause. PFS was defined as time from randomization to first documented disease progression or death on study treatment, whichever occurred first. Event-time distributions were estimated using the Kaplan-Meier method. RESULTS: Herbst et al2 and Reck et al6 compared traditional chemotherapy plus bevacizumab to traditional chemotherapy plus placebo, and Sandler et al3 compared traditional chemotherapy plus bevacizumab to traditional chemotherapy alone. Herbst et al2 failed to find a significant difference in OS or PFS between subjects using adjuvant bevacizumab and those using traditional chemotherapy. Reck et al6 was unable to assess OS; however, the investigators reported that PFS was significantly improved with the addition of bevacizumab to traditional chemotherapy. Sandler et al3 established that the addition of bevacizumab to traditional chemotherapy has statistically significant survival benefits in patients with NSCLC. CONCLUSIONS: From the research performed and results obtained, the evidence is inconclusive and conflicting to support the use of bevacizumab as adjuvant chemotherapy for stage IIIb or IV NSCLC. With inconsistencies and differing results among the three RCTs, further research would be helpful to confirm or negate the question of whether bevacizumab is actually beneficial as adjuvant therapy. In addition to researching the efficacy and safety of bevacizumab as adjuvant chemotherapy, it would be advantageous to study the efficacy and safety of bevacizumab as monotherapy. Further research is warranted to obtain more conclusive data

Long-term morbidity and follow-up after choledochal malformation surgery; A plea for a quality of life study

Much about the aetiology, pathophysiology, natural course and optimal treatment of choledochal malformation remains under debate. Surgeons continuously strive to optimize their roles in the management of choledochal malformation. Nowadays the standard treatment is complete cyst excision followed by Rouxen-Y hepaticojejunostomy, be it via a laparotomy, laparoscopy or robot-assisted procedure. Whatever surgical endeavor is undertaken, it will be a major operation, with significant morbidity. It is important to realize that especially in asymptomatic cases, this is considered prophylactic surgery, aimed at preventing symptoms but even more important the development of malignancy later in life. A clear overview of long-term outcomes is therefore necessary. This paper aims to review the long-term outcomes after surgery for choledochal malformation. We will focus on biliary complications such as cholangitis, the development of malignancy and quality of life. We will try and identify factors related to a worse outcome. Finally, we make a plea for a large scale study into quality and course of life after resection of a choledochal malformation, to help patients, parents and their treating physicians to come to a well-balanced decision regarding the treatment of a choledochal malformation. (C) 2020 The Authors. Published by Elsevier Inc

Tinnitus-related dissociation between cortical and subcortical neural activity in humans with mild to moderate sensorineural hearing loss

AbstractTinnitus is a phantom sound percept that is strongly associated with peripheral hearing loss. However, only a fraction of hearing-impaired subjects develops tinnitus. This may be based on differences in the function of the brain between those subjects that develop tinnitus and those that do not. In this study, cortical and sub-cortical sound-evoked brain responses in 34 hearing-impaired chronic tinnitus patients and 19 hearing level-matched controls were studied using 3-T functional magnetic resonance imaging (fMRI). Auditory stimuli were presented to either the left or the right ear at levels of 30–90 dB SPL. We extracted neural activation as a function of sound intensity in eight auditory regions (left and right auditory cortices, medial geniculate bodies, inferior colliculi and cochlear nuclei), the cerebellum and a cinguloparietal task-positive region. The activation correlated positively with the stimulus intensity, and negatively with the hearing threshold. We found no differences between both groups in terms of the magnitude and lateralization of the sound-evoked responses, except for the left medial geniculate body and right cochlear nucleus where activation levels were elevated in the tinnitus subjects. We observed significantly reduced functional connectivity between the inferior colliculi and the auditory cortices in tinnitus patients compared to controls. Our results indicate a failure of thalamic gating in the development of tinnitus

Intraocular and intracranial pressure in glaucoma patients taking acetazolamide

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ

Meta-analysis of risk of developing malignancy in congenital choledochal malformation

BackgroundCholedochal malformations comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. Choledochal malformation is generally considered a premalignant condition, but reliable data on the risk of malignancy and optimal surgical treatment are lacking. The objective of this systematic review was to assess the prevalence of malignancy in patients with choledochal malformation and to differentiate between subtypes. In addition, the risk of malignancy following cystic drainage versus complete cyst excision was assessed. MethodsA systematic review of PubMed and Embase databases was performed in accordance with the PRISMA statement. A meta-analysis of the risk of malignancy following cystic drainage versus complete cyst excision was undertaken in line with MOOSE guidelines. Prevalence of malignancy was defined as the rate of biliary cancer before resection, and malignant transformation as new-onset biliary cancer after surgery. ResultsEighteen observational studies were included, reporting a total of 2904 patients with a median age of 36 years. Of these, 312 in total developed a malignancy (107 per cent); the prevalence of malignancy was 73 per cent and the rate of malignant transformation was 34 per cent. Patients with types I and IV choledochal malformation had an increased risk of malignancy (P = 0016). Patients who underwent cystic drainage had an increased risk of developing biliary malignancy compared with those who had complete cyst excision, with an odds ratio of 397 (95 per cent c.i. 240 to 655). ConclusionThe risk of developing malignancy among patients with choledochal malformation was almost 11 per cent. The malignancy risk following cystic drainage surgery was four times higher than that after complete cyst excision. Complete surgical resection is recommended in patients with choledochal malformation. Choledochal cysts should be resecte

Associations between tinnitus and glaucoma suggest a common mechanism:A clinical and population-based study

The purpose of this study was to determine if there is an association between tinnitus and glaucoma. We tested this by first completing a clinic-based cross-sectional questionnaire study in which we sent a series of tinnitus-related questions to glaucoma patients and healthy subjects, and then followed up with a large population-based cross-sectional study in which glaucoma and tinnitus were also assessed by questionnaire. For the clinical study, we received 209 responses from glaucoma patients and 109 responses from healthy subjects (primarily the spouses of the patients). For the population-based study, we evaluated 79,866 participants. Logistic regression models were used to test the relationship between glaucoma and tinnitus; the clinical study analysis was adjusted for age, gender, BMI, hypertension, and diabetes and the population-based study was adjusted for these same variables with the addition of socioeconomic status and subjective hearing loss. For the clinical study, glaucoma patients had an 85% increase in odds for tinnitus (adjusted OR 1.85, 95% CI 1.10 to 3.05). The effect did not depend on pretreatment intraocular pressure, and the associated symptoms were not pulsatile in nature. For the population-based study, glaucoma patients had a 19% increase in odds for tinnitus (adjusted OR 1.19, 95% CI 1.02 to 1.40). Overall, our results suggest that those with glaucoma are more likely to have tinnitus than those without glaucoma. These results provide hypotheses for a mechanism involved in both tinnitus and glaucoma. One possible mechanism could be vascular dysregulation due to impairment of nitric oxide production

Guidelines for incorporating scientific knowledge and practice on rare diseases into higher education: neuronal ceroid lipofuscinoses as a model disorder model disorder.

This article addresses the educational issues associated with rare diseases (RD) and in particular the Neuronal Ceroid Lipofuscinoses (NCLs, or CLN diseases) in the curricula of Health Sciences and Professional's Training Programs. Our aim is to develop guidelines for improving scientific knowledge and practice in higher education and continuous learning programs. Rare diseases (RD) are collectively common in the general populationwith 1 in 17 people affected by a RDin their lifetime. Inherited defects in genes involved in metabolism are the commonest group of RD with over 8000 known inborn errors of metabolism. The majority of these diseases are neurodegenerative including the NCLs. Any professional training program on NCL must take into account the medical, social and economic burdens related to RDs. To address these challenges and find solutions to themit is necessary that individuals in the government and administrative authorities, academia, teaching hospitals and medical schools, the pharmaceutical industry, investment community and patient advocacy groups all work together to achieve these goals. The logistical issues of including RD lectures in university curricula and in continuing medical education should reflect its complex nature. To evaluate the state of education in the RD field, a summary should be periodically up dated in order to assess the progress achieved in each country that signed up to the international conventions addressing RD issues in society. It is anticipated that auditing current practice will lead to higher standards and provide a framework for those educators involved in establishing RD teaching programs world-wide.publishedVersio