Evaluation of MV140 in preventing recurrent urinary tract infections: a multicentre double-blind randomized controlled trial protocol.

OBJECTIVES: To determine, firstly, whether MV140 reduces rates of recurrent urinary tract infections (rUTIs) in patients older than 65 years, measured as the number of urinary tract infections (UTIs) detected over 12 months following the completion of a 3-month treatment course and, additionally, to assess the number of re-admissions to the emergency department, the rate of antibiotic use for UTIs, the safety profile of MV140, and quality of life. MATERIALS AND METHODS: This is a multicentre, double-blind, randomized controlled trial with two arms. Patients will be randomized and allocated to receive either a 3-month course of MV140 or placebo (two sublingual sprays daily). Participants will have 3-monthly consultations with the investigator for 12 months to assess differences in rates of rUTIs between the two groups. Study candidates will be identified and recruited from inpatient and outpatient clinics across Sydney via referral to the investigation team. After obtaining consent, participants will undergo initial study consultations including urine microscopy and culture, uroflowmetry, and bladder scan to assess postvoid residual urine volume. Participants will be randomized and provided with a unique trial number. Electronic medical records will be reviewed to collect relevant information. Participants will be provided with a study diary to record relevant data. RESULTS: Follow-up consultations will be conducted every 3 months for a 12-month duration, during which the study diary will be reviewed. These follow-up consultations will primarily occur via telephone review, however, there will be flexibility for in-person reviews for participants who find telephone consultation prohibitively difficult. CONCLUSION: This is a multicentre, double-blinded, randomised control trial, the first in Australia to assess the safety and efficacy of MV140 Uromune vaccine in prevention of recurrent UTIs. Results have been promissing in the global literatures.

Urology case report - Emergency penectomy for the transfeminine patient.

Management of gender dysphoria and healthcare for transgender and non-binary patients is a growing field in Australia and abroad. Currently, gender-affirming surgery is not offered under Australia's national public health insurance. We present an unusual case of emergency penectomy required for a 57-year-old woman assigned-male-at-birth from rural Australia after a self-inflicted chemical burn. This case report outlines the surgical challenges of partial penectomy and neo meatus formation to allow for future gender-affirming surgery and highlights the lack of infrastructure within the public healthcare system for management of gender dysphoria both in rural and metropolitan settings.

Survival benefits with EPIC in addition to HIPEC for low grade appendiceal neoplasms with pseudomyxoma peritonei: a propensity score matched study.

Objectives: Appendiceal cancer is a rare malignancy, occurring in roughly 1.2 per 100,000 per year. Low grade appendiceal neoplasams (LAMN) in particular can lead to pseudomyxoma peritonei (PMP), and respond poorly to systemic chemotherapy. Standard treatment includes cytoreduction surgery (CRS) with addition of heated intraoperative peritoneal chemotherapy (HIPEC). Several centres include early postoperative intraperitoneal chemotherapy (EPIC) however; the literature is mixed on the benefits. We aim to examine the benefits of additional EPIC through a propensity-matched analysis. Methods: Patients with LAMN with PMP who underwent cytoreductive surgery at St George hospital between 1996 and 2020 were included in this retrospective analysis. Propensity score matching was performed with the following used to identify matched controls; sex, age, American Society of Anesthesiologists (ASA) grade, peritoneal cancer index (PCI) and morbidity grade. Outcomes measured included length of stay and survival. Results: A total of 224 patients were identified of which 52 received HIPEC alone. Propensity matching was performed to identify 52 matched patients who received HIPEC + EPIC. Those receiving HIPEC + EPIC were younger at 54.3 vs. 58.4 years (p=0.044). There was a median survival benefit of 34.3 months for HIPEC + EPIC (127.3 vs. 93.0 months, p=0.02). Median length of stay was higher in those who received EPIC (25.0 vs. 23.5 days, p=0.028). Conclusions: In LAMN with PMP, the addition of EPIC to HIPEC with CRS improves overall survival in propensity score matched cases but results in prolonged hospitalisation. The use of EPIC should still be considered in selected patients.

Differentiation of renal masses with multi-parametric MRI: the de Silva St George classification scheme.

PURPOSE: To develop a system for multi-parametric MRI to differentiate benign from malignant solid renal masses and assess its accuracy compared to the gold standard of histopathological diagnosis. METHODS: This is a retrospective analysis of patients who underwent 3 Tesla mpMRI for further assessment of small renal tumours with specific scanning and reporting protocol incorporating T2 HASTE signal intensity, contrast enhancement ratios, apparent diffusion coefficient and presence of microscopic/macroscopic fat. All MRIs were reported prior to comparison with histopathologic diagnosis and a reporting scheme was developed. 2 × 2 contingency table analysis (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)), Fisher Exact test were used to assess the association between suspicion of malignancy on mpMRI and histopathology, and descriptive statistics were performed. RESULTS: 67 patients were included over a 5-year period with a total of 75 renal masses. 70 masses were confirmed on histopathology (five had pathognomonic findings for angiomyolipomas; biopsy was therefore considered unethical, so these were included without histopathology). Three patients were excluded due to a non-diagnostic result, non-standardised imaging and one found to be an organising haematoma rather than a mass. Therefore 72 cases were included in analysis (in 64 patients, with seven patients having multiple tumours). Unless otherwise specified, all further statistics refer to individual tumours rather than patients. 52 (72.2%) were deemed 'suspicious or malignant' and 20 (27.8%) were deemed 'benign' on mpMRI. 51 cases (70.8%) had renal cell carcinoma confirmed. The sensitivity, NPV, specificity and PPV for MRI for detecting malignancy were 96.1%, 90%, 85.7% and 94.2% respectively, Fisher's exact test demonstrated p < 0.0001 for the association between suspicion of malignancy on MRI and histopathology. CONCLUSION: The de Silva St George classification scheme performed well in differentiating benign from malignant solid renal masses, and may be useful in predicting the likelihood of malignancy to determine the need for biopsy/excision. Further validation is required before this reporting system can  be recommended for clinical use.

Does the introduction of pre-operative cardiopulmonary exercise testing in radical cystectomy delay or alter surgical care?

Objectives: To assess if the introduction of routine pre-operative cardiopulmonary exercise testing (CPET) in radical cystectomy has delayed surgical intervention. Materials and Methods: A prospective database of patients undergoing radical cystectomy in our local health network was maintained. A retrospective analysis of two years (2018-2020) included 38 patients. Of these, 15 patients had CPET pre-operatively, and a direct comparison was performed. Results: The mean time from diagnosis to cystectomy was 95 days in patients who did not have CPET compared to 110 days for those who did (p = 0.32), with comparable rates of neoadjuvant chemotherapy (NAC) (62.5% and 64.29%). Average length of stay was 18.6 days compared with 13.87 (p = 0.16), favouring the CPET group. The CPET group also had a lower readmission rate within 30 days (13.33% compared with 21.05%, p = 0.35). Cause-specific mortality within 90 days was 10.2% and within the study timeframe was 36.84% (estimated 5-year mortality rate 43-65%). Within the CPET group, eight had an anaerobic threshold (AT) of <11 ml/kg/min (range 6.3-10.5): Of these, 50% had Clavien-Dindo complications of grade 2 or higher and the 90-day mortality rate was 37.5% (cf. 0% in those with AT > 11 ml/kg/min in this series). Conclusion: CPET is a valuable risk evaluation tool. This study suggested that CPET contributed to a minor non-significant delay to surgery, however was associated with reduced length of stay and readmission rates, and was a valuable risk evaluation tool. We found that CPET AT <11 ml/kg/min is associated with higher rates of patient morbidity and perioperative mortality.

Outcomes of poorly differentiated and plasmacytoid variant bladder urothelial carcinoma.

Objectives: The aim of this study is to assess the course and management of poorly differentiated bladder urothelial carcinoma (UC), including plasmacytoid UC (PUC), in our local area. Although bladder cancer is relatively common, PUC is a rare and aggressive subtype with a poor prognosis that is still poorly understood. Materials and Methods: A retrospective assessment of all poorly differentiated high-grade UC over the last 15 years (2005-2020) in the Hunter New England area was completed. In total, 37 patients were included, and PUC variant was compared with the remaining poorly differentiated UC. Results: Of the included cases, eight were PUC, nine squamous variant, two neuroendocrine, and one sarcomatoid. Overall, 23 cases proceeded to cystectomy, 15 had chemotherapy (six neoadjuvant), and 11 had radiation therapy. In the PUC subgroup, three had metastatic disease at diagnosis (37.5%). Of the three PUC patients who underwent cystectomy, all were upstaged. Two PUC cases had adjuvant chemotherapy, and one case had radiation. Within the follow-up period, the PUC group had a cause-specific mortality of 50% with a mean survival in these patients of 202 days, compared with 37.9% cause-specific mortality with survival of 671.55 days (p = 0.23) in all other undifferentiated UC cases; 5-year cause-specific mortality with Kaplan-Meier analysis was estimated at 26% compared with 59%, respectively (p = 0.058). Conclusion: Poorly differentiated UC is demonstrated to have a poor prognosis with a high mortality rate, particularly when PUC is present. Given the rarity of these variants, further studies are necessary to explore the impact of current treatment options.

ELISA-based quantification of neurotrophic growth factors in urine from prostate cancer patients.

Non-invasive procedures are needed for prostate cancer management, and urine represents a potential source of new biomarkers with translational value. Recent evidence has shown that the growth of new nerves in the tumor microenvironment is essential to prostate cancer progression. Neurotrophic growth factors are expressed by prostate cancer cells and contribute to prostate tumor innervation, but their presence in urine is unclear. In the present study, we have assayed the concentration of neurotrophic factors in the urine of prostate cancer patients. Urine was collected from a prospective cohort of 45 men with prostate cancer versus 30 men without cancer and enzyme-linked immunosorbent assay was used to quantify nerve growth factor (NGF) and its precursor proNGF, brain-derived neurotrophic factor (BDNF) and proBDNF, neurotrophin-3, neurotrophin-4/5, and glia-derived neurotrophic growth factor. The results show that neurotrophic factors are detectable in various concentrations in both cancer and healthy urine, but no significant difference was found. Also, no association was observed between neurotrophic factor concentrations and prostate cancer grade. This study is the first quantification of neurotrophins in urine, and although no significant differences were observed between prostate cancer patients versus those without prostate cancer, or between prostate cancers of various grades, the potential value of neurotrophins for prostate cancer diagnosis and prognosis warrants further investigations in larger patient cohorts.

The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers.

BACKGROUND: MRI is playing an increasing role in risk stratification and non-invasive diagnosis of the undifferentiated small renal mass. This study was designed to assess the reliability of MRI in diagnostic evaluation of renal masses, specifically characterising lesions with diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values. METHODS: This is a retrospective analysis of patients undergoing MRI as part of their clinical workup for a renal mass suspicious for renal cell carcinoma (RCC) on CT or ultrasound followed by biopsy and/or surgical excision. All cases were conducted on 3 Tesla MRI, with conventional breath-held sequences, DWI and dynamic contrast enhanced phases. Tumour regions of interest were evaluated on ADC maps and compared with T2 weighted and post-contrast images. RESULTS: Of the 66 renal tumours included, 33 (50.0%) were Clear Cell RCC, 11 (16.7%) were Oncocytoma, nine (13.6%) were Angiomyolipoma (AML), nine (13.6%) were Papillary RCC and four (6.1%) were Chromophobe RCC. Oncocytoma had the largest ADC values, significantly larger than AMLs and all RCC subtypes (p < 0.001). The average ADC value was also significantly larger in Clear Cell RCCs compared to AMLs, and other RCC subtypes (p < 0.001). CONCLUSIONS: MRI with DWI/ADC imaging may aid the differentiation of oncocytomas from RCCs and stratify RCC subtypes, Further studies are required to validate these findings. TRIAL REGISTRATION: Not applicable/retrospective study.

Bladder perforation: A rare complication of retention management.

A healthy 25 year old woman presented with acute urinary retention following alcohol ingestion. A 14 french foley catheter drained over 1 L of haematuria immediately. Due to worsening and persistent abdominal pain, CT and ultrasound imaging was performed, demonstrating only a small amount of free fluid. Diagnostic laparoscopy revealed an intraperitoneal bladder perforation with the foley catheter visible. The bladder defect was repaired and she recovered well. This is a rare case of likely iatrogenic bladder perforation from simple catheterisation without predisposing comorbidities, highlighting the importance of correct technique and awareness of potential complications.

Chemical shift imaging in the identification of those renal tumours that contain microscopic fat and the utility of multiparametric MRI in their differentiation.

INTRODUCTION: The aim of this study was to assess the qualitative and MRI findings of renal tumours, to determine which lesions contain microscopic fat, one of the potential differentiating factors between tumour types. METHODS: 73 patients who underwent 3 Tesla MRI including chemical shift imaging, with subsequent biopsy or excision for histopathological diagnosis, were included in the study. The images were reviewed for a decrease in signal intensity (SI) on the opposed phase compared with the in-phase gradient echo T1 images, indicating the presence of microscopic fat. The chemical shift index was then calculated as a percentage of SI change and compared with the pathological diagnosis. RESULTS: In total, 38 (52%) of lesions demonstrated a decrease in SI, consistent with microscopic fat. Microscopic fat was found in 28 (80%) clear cell renal cell carcinomas (RCCs), 6 (66.7%) angiomyolipomas, 2 (20%) papillary RCCs, 1 (20%) chromophobe RCC and 1 (9.1%) oncocytoma. Pairwise comparison of means indicated that the amount of microscopic fat was significantly larger only for angiomyolipomas compared with clear cell RCCs (P < 0.001) and other renal lesions (P < 0.001). CONCLUSIONS: A decrease in SI on opposed phase compared with in-phase chemical shift imaging favours the diagnosis of either clear cell RCC or an angiomyolipoma. When combined with other parameters in mpMRI, this may aid differentiation of benign from malignant tumours and differentiation of aggressive from indolent RCC subtypes. This may be of value where biopsy is non-diagnostic, not feasible due to location or in high-risk patients.

What not to expect when you're expecting - Postpartum proximal ureteric rupture: A case report.

INTRODUCTION: Spontaneous ureteric rupture is an extremely rare cause of acute abdominal pain in the intrapartum and postpartum period. We present the case of a right ureteric rupture diagnosed immediately postpartum. CASE: A 23-year-old woman in her second pregnancy (who had had a previous caesarean section) developed acute-onset right-flank pain 12 h after vaginal delivery. A contrast computerized tomography scan suggested a ureteric injury; ureteroscopy diagnosed a proximal ureteric rupture and a stent was placed. DISCUSSION: This case outlines an extremely rare cause of abdominal pain in the peripartum. There can be serious complications, including urinoma, abscess and sepsis, and therefore the diagnosis should not be delayed.

Novel approach to locating a hypoplastic kidney in a unique variant of uterine didelphys syndrome presenting with continuous incontinence.

Mullerian abnormalities such as uterine didelphys have an association with renal abnormalities. Ureteric ectopia must be considered as a differential diagnosis of incontinence. We describe the case of a 21-year-old woman who presented with low volume continuous incontinence with a history of right renal agenesis and uterus didelphys. A right kidney was not identified on CT intravenous pyelogram but excretory phase images suggested the presence of a right ureter. Diethylenetriaminepentaacetic acid renogram confirmed an area of perfusion consistent with a poorly functioning right kidney remnant. Cystoscopic investigation demonstrated an orthotopic left ureteric orifice, and an ectopic right ureteric orifice was identified in the posterior fornix of the right vagina. A laparoscopic right nephrectomy was performed, with a new application of indocyanine green aiding in identification of the right hypoplastic kidney with fluorescence imaging. The patient recovered well postoperatively and experienced complete resolution of incontinence, with preserved normal renal function.

Mesh versus non-mesh for inguinal and femoral hernia repair.

BACKGROUND: This is an update of a Cochrane Review first published in 2001.Hernias are protrusions of all or part of an organ through the body wall that normally contains it. Groin hernias include inguinal (96%) and femoral (4%) hernias, and are often symptomatic with discomfort. They are extremely common, with an estimated lifetime risk in men of 27%. Occasionally they may present as emergencies with complications such as bowel incarceration, obstruction and strangulation. The definitive treatment of all hernias is surgical repair, inguinal hernia repair being one of the most common surgical procedures performed. Mesh (hernioplasty) and the traditional non-mesh repairs (herniorrhaphy) are commonly used, with an increasing preference towards mesh repairs in high-income countries. OBJECTIVES: To evaluate the benefits and harms of different inguinal and femoral hernia repair techniques in adults, specifically comparing closure with mesh versus without mesh. Outcomes include hernia recurrence, complications (including neurovascular or visceral injury, haematoma, seroma, testicular injury, infection, postoperative pain), mortality, duration of operation, postoperative hospital stay and time to return to activities of daily living. SEARCH METHODS: We searched the following databases on 9 May 2018: Cochrane Colorectal Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (Issue 1), Ovid MEDLINE (from 1950), Ovid Embase (from 1974) and Web of Science (from 1900). Furthermore, we checked the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for trials. We applied no language or publication restrictions. We also searched the reference lists of included trials and review articles. SELECTION CRITERIA: We included randomised controlled trials of mesh compared to non-mesh inguinal or femoral hernia repairs in adults over the age of 18 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Where available, we collected information on adverse effects. We presented dichotomous data as risk ratios, and where possible we calculated the number needed to treat for an additional beneficial outcome (NNTB). We presented continuous data as mean difference. Analysis of missing data was based on intention-to-treat principles, and we assessed heterogeneity using an evaluation of clinical and methodological diversity, Chi2 test and I2 statistic. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We included 25 studies (6293 participants) in this review. All included studies specified inguinal hernias, and two studies reported that femoral hernias were included.Mesh repair probably reduces the risk of hernia recurrence compared to non-mesh repair (21 studies, 5575 participants; RR 0.46, 95% CI 0.26 to 0.80, I2 = 44%, moderate-quality evidence). In absolute numbers, one hernia recurrence was prevented for every 46 mesh repairs compared with non-mesh repairs. Twenty-four studies (6293 participants) assessed a wide range of complications with varying follow-up times. Neurovascular and visceral injuries were more common in non-mesh repair groups (RR 0.61, 95% CI 0.49 to 0.76, I2 = 0%, NNTB = 22, high-quality evidence). Wound infection was found slightly more commonly in the mesh group (20 studies, 4540 participants; RR 1.29, 95% CI 0.89 to 1.86, I2 = 0%, NNTB = 200, low-quality evidence). Mesh repair reduced the risk of haematoma compared to non-mesh repair (15 studies, 3773 participants; RR 0.88, 95% CI 0.68 to 1.13, I2 = 0%, NNTB = 143, low-quality evidence). Seromas probably occur more frequently with mesh repair than with non-mesh repair (14 studies, 2640 participants; RR 1.63, 95% CI 1.03 to 2.59, I2 = 0%, NNTB = 72, moderate-quality evidence), as does wound swelling (two studies, 388 participants; RR 4.56, 95% CI 1.02 to 20.48, I2 = 33%, NNTB = 72, moderate-quality evidence). The comparative effect on wound dehiscence is uncertain due to wide confidence intervals (two studies, 329 participants; RR 0.55, 95% CI 0.12 to 2.48, I2 = 37% NNTB = 77, low-quality evidence). Testicular complications showed nearly equivocal results; they probably occurred slightly more often in the mesh group however the confidence interval around the effect was wide (14 studies, 3741 participants; RR 1.06, 95% CI 0.63 to 1.76, I2 = 0%, NNTB = 2000, low-quality evidence). Mesh reduced the risk of postoperative urinary retention compared to non-mesh (eight studies, 1539 participants; RR 0.53, 95% CI 0.38 to 0.73, I2 = 56%, NNTB = 16, moderate-quality evidence).Postoperative and chronic pain could not be compared due to variations in measurement methods and follow-up time (low-quality evidence).No deaths occurred during the follow-up periods reported in the seven studies (2546 participants) reporting this outcome (high-quality evidence).The average operating time was longer for non-mesh repairs by a mean of 4 minutes 22 seconds, despite wide variation across the studies regarding size and direction of effect, thus this result is uncertain (20 studies, 4148 participants; 95% CI -6.85 to -1.60, I2= 97%, very low-quality evidence). Hospital stay may be shorter with mesh repair, by 0.6 days (12 studies, 2966 participants; 95% CI -0.86 to -0.34, I2 = 98%, low-quality evidence), and participants undergoing mesh repairs may return to normal activities of daily living a mean of 2.87 days sooner than those with non-mesh repair (10 studies, 3183 participants; 95% CI -4.42 to -1.32, I2 = 96%, low-quality evidence), although the results of both these outcomes are also limited by wide variation in the size and direction of effect across the studies. AUTHORS' CONCLUSIONS: Mesh and non-mesh repairs are effective surgical approaches in treating hernias, each demonstrating benefits in different areas. Compared to non-mesh repairs, mesh repairs probably reduce the rate of hernia recurrence, and reduce visceral or neurovascular injuries, making mesh repair a common repair approach. Mesh repairs may result in a reduced length of hospital stay and time to return to activities of daily living, but these results are uncertain due to variation in the results of the studies. Non-mesh repair is less likely to cause seroma formation and has been favoured in low-income countries due to low cost and reduced availability of mesh materials. Risk of bias in the included studies was low to moderate and generally handled well by study authors, with attention to details of allocation, blinding, attrition and reporting.

Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. Chronic obstructive pulmonary disease is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis. OBJECTIVES: To assess the effectiveness of an oral, whole-cell NTHi vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 1), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), CINAHL (1981 to January 2017), LILACS (1985 to January 2017), and Web of Science (1955 to January 2017). We also searched trials registries and contacted authors of trials requesting unpublished data. SELECTION CRITERIA: We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes. MAIN RESULTS: We identified six placebo-controlled randomised controlled trials with a total of 557 participants. These trials investigated the efficacy of enteric-coated, killed preparations of H influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regimen in all trials consisted of at least three courses of formalin-killed H influenzae in enteric-coated tablets taken at intervals (e.g. days 0, 28, and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD (risk ratio (RR) 0.79, 95% confidence interval (CI) 0.57 to 1.10; P = 0.16). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12; P = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with the placebo group.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44; P < 0.001). There was no significant difference between the groups with regard to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04; P = 0.97). Adverse events were reported in five trials but were not necessarily related to the vaccine; a point estimate is suggestive that they occurred more frequently in the vaccine group, however this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92; P = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo). AUTHORS' CONCLUSIONS: Analyses demonstrate that NTHi oral vaccination of people with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence was mixed, and the individual trials that showed a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.

Full medical program fees and medical student career intention.

OBJECTIVE: To explore the future career preferences of Commonwealth-supported place (CSP) and full-fee paying (FFP) medical students in Australia. DESIGN, SETTING AND PARTICIPANTS: Data from the Medical Schools Outcomes Database and Longitudinal Tracking (MSOD) Project exit questionnaire for CSP and FFP students who graduated between 2008 and 2011 were analysed using logistic regression. The influence of age, sex, marital status, rural background and fee-paying status on future career preference were explored. MAIN OUTCOME MEASURE: Future career preference (location and specialty) at graduation. RESULTS: Compared with CSP students, domestic FFP students were more likely to nominate as their first preference both urban locations (odds ratio [OR], 5.58; 95% CI, 2.04-15.26; P < 0.001) and higher-income specialties (OR, 1.37; 95% CI, 1.07-1.75; P < 0.05), and less likely to nominate as their first preference in-need specialties (OR, 0.72; 95% CI, 0.52-1.00; P < 0.05), specifically general practice (OR, 0.71; 95% CI, 0.52-0.99; P < 0.05). There was a significant domestic FFP student by marital status interaction effect, such that domestic FFP students who were married or partnered on exit from medical school were more likely to prefer a rural location (OR, 0.64; 95% CI, 0.44-0.95; P < 0.05). Also, students who were married or partnered were less likely to select a one of the higher-income specialties as their first preference (OR, 0.77; 95% CI, 0.64-0.92; P < 0.01). A rural background increased preferences for rural location (OR, 0.18; 95% CI, 0.15-0.22; P < 0.001) and in-need specialties (OR, 1.28; 95% CI, 1.04-1.57; P < 0.05), and being older on entry to medical school also increased preferences for rural location (OR, 0.96; 95% CI, 0.95-0.98; P < 0.001) and in-need specialties (OR, 1.03; 95% CI, 1.01-1.04; P < 0.01). International FFP students were more likely to prefer urban practice (OR, 1.79; 95% CI, 1.19-2.72; P < 0.01). CONCLUSION: Domestic FFP graduates are less likely to prefer careers in rural locations and in lower-paid and in-need specialties, particularly general practice. Current workforce implications might be minor, but if fees for CSP students increase or more FFP places become available, potential impacts on workforce distribution will need to be considered.

Haemophilus influenzae oral vaccination for preventing acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease.

BACKGROUND: Chronic bronchitis and chronic obstructive pulmonary disease (COPD) are serious conditions in which patients are predisposed to viral and bacterial infections resulting in potentially fatal acute exacerbations. COPD is defined as a lung disease characterised by obstruction to lung airflow that interferes with normal breathing. Antibiotic therapy has not been particularly useful in eradicating bacteria such as non-typeable Haemophilus influenzae (NTHi) because they are naturally occurring flora of the upper respiratory tract in many people. However, they can cause opportunistic infection. An oral NTHi vaccine has been developed to protect against recurrent infective acute exacerbations in chronic bronchitis. OBJECTIVES: To assess the effectiveness of an oral, whole-cell, non-typeable H. influenzae (NTHi) vaccine in protecting against recurrent episodes of acute exacerbations of chronic bronchitis and COPD in adults. To assess the effectiveness of NTHi vaccine in reducing NTHi colonising the respiratory tract during recurrent episodes of acute exacerbations of COPD. SEARCH METHODS: We searched the following databases: CENTRAL (2014, Issue 6), MEDLINE (1946 to July week 3, 2014), EMBASE (1974 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014) and Web of Science (1955 to July 2014). We also searched trials registries and contacted authors of trials requesting unpublished data. SELECTION CRITERIA: We included randomised controlled trials comparing the effects of an oral monobacterial NTHi vaccine in adults with recurrent acute exacerbations of chronic bronchitis or COPD when there was overt matching of the vaccine and placebo groups on clinical grounds. The selection criteria considered populations aged less than 65 years and those older than 65 years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from original records and publications for incidence and severity of bronchitis episodes and carriage rate of NTHi measured in the upper respiratory tract, as well as data relevant to other primary and secondary outcomes. MAIN RESULTS: We identified six placebo-controlled randomised controlled trials with a total of 557 participants. They investigated the efficacy of enteric-coated, killed preparations of H. influenzae in populations prone to recurrent acute exacerbations of chronic bronchitis or COPD. The vaccine preparation and immunisation regime in all trials consisted of at least three courses of formalin-killed H. influenzae in enteric-coated tablets taken at intervals (for example, days 0, 28 and 56). Each course generally consisted of two tablets taken after breakfast over three consecutive days. In all cases the placebo groups took enteric-coated tablets containing glucose. Risk of bias was moderate across the studies, namely due to the lack of information provided about methods and inadequate presentation of results.Meta-analysis of the oral NTHi vaccine showed a small, non-statistically significant reduction in the incidence of acute exacerbations of chronic bronchitis or COPD by 2.048% (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.84 to 1.12, P value = 0.68). There was no significant difference in mortality rate between the vaccine and placebo groups (odds ratio (OR) 1.62, 95% CI 0.63 to 4.12, P value = 0.31).We were unable to meta-analyse the carriage levels of NTHi in participants as each trial reported this result using different units and tools of measurement. Four trials showed no significant difference in carriage levels, while two trials showed a significant decrease in carriage levels in the vaccinated group compared with placebo.Four trials assessed severity of exacerbations measured by requirement for antibiotics. Three of these trials were comparable and when meta-analysed showed a statistically significant 80% increase in antibiotic courses per person in the placebo group (RR 1.81, 95% CI 1.35 to 2.44, P value < 0.0001). There was no significant difference between the groups with regards to hospital admission rates (OR 0.96, 95% CI 0.13 to 7.04, P value = 0.97). Adverse events were reported in all six trials with a point estimate suggestive that they occurred more frequently in the vaccine group, however, this result was not statistically significant (RR 1.43, 95% CI 0.70 to 2.92, P value = 0.87). Quality of life was not meta-analysed but was reported in two trials, with results at six months showing an improvement in quality of life in the vaccinated group (scoring at least two points better than placebo). AUTHORS' CONCLUSIONS: Analyses demonstrate that NTHi oral vaccination of patients with recurrent exacerbations of chronic bronchitis or COPD does not yield a significant reduction in the number and severity of exacerbations. Evidence is mixed and the individual trials that show a significant benefit of the vaccine are too small to advocate widespread oral vaccination of people with COPD.