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Bladder cancer encapsulates a wide spectrum of disease severities, with non-muscle invasive bladder cancer (NMIBC) representing an entirely different entity from muscle-invasive disease. Bacillus Calmette-Guérin (BCG) is one of the most successful intravesical treatment methods for patients diagnosed. However, a considerable proportion of patients fail to respond to BCG treatment. Given the propensity for recurrence in patients with high-risk bladder cancer, these patients present with surgical dilemmas. There is currently no gold standard for salvage treatment post-BCG failure or unified definition as to what that means. In this review, we discuss the mechanisms of action and pathophysiology of BCG, potential theories behind BCG failure, and the scope of novel treatments for this surgical conundrum., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023 Published by Elsevier B.V. on behalf of Chinese Medical Association (CMA).)

Objective: In view of changing landscape of surgical treatment for LUTS secondary to BPE, this audit was undertaken to assess key aspects of the processes and outcomes of the current interventional treatments for BPE, across different units in the UK., Materials and Method: A multi-institutional snapshot audit was conducted for patients undergoing interventions for LUTS/BPE over 8-week period. Using Delphi process two-part proforma was designed to capture data., Results: 529 patients were included across 20 NHS trusts in England and Wales. Median age was 73 years. Indications for surgery were acute retention (47%) and LUTS (45%). 80% of patients had prior medical therapy. TURP formed the commonest procedure. 27% patients had <23 hour hospital stay. Immediate (21%) and delayed (18%) complications were Clavien-Dindo <2 category. High proportion of patients reported residual symptoms. Type and indication of surgery were significant predictor of complications, length of stay and failure of TWOC outcomes, on multivariate analyses. There were variations in departmental processes, 50% centres used PROMs., Conclusion: Monopolar TURP still remains the commonest intervention for BPE. Most departments are adopting newer technologies. The audit identified opportunities for development of consistent, effective and patient centric practices as well as need for large-scale focused studies.

A general northward shift in marine species distributions has been observed in the western North Atlantic Ocean, which may have significant ecological consequences. Large coastal sharks can have wide migratory distributions but show fidelity to specific nursery habitats. Here we show evidence for nursery range expansion into Pamlico Sound, North Carolina by a marine apex predator, the Bull Shark (Carcharhinus leucas). Previous assessments have shown little to no use of estuarine North Carolina waters as nursery habitat by Bull Sharks from 1965-2011. Juvenile sharks were rarely captured in a fishery-independent gillnet survey conducted by the North Carolina Division of Marine Fisheries (NCDMF) from 2003-2011, but were present every year from 2011-2016. Juvenile Bull Shark presence in the Sound was strongly related to early summer temperatures and late summer salinities, which have increased in the estuary over the 13 survey years, and further evidence for increasing water temperatures in Pamlico Sound was found in a 45-year data set for the NCDMF estuarine trawl survey. These results suggest that increasing water temperature and salinity have allowed Bull Sharks to expand their nursery habitat. This shift will have unknown, but potentially strong, impacts on both the local ecosystem and interactions with humans.

Estuaries function as important nursery and foraging habitats for many coastal species, including highly migratory sharks. Pamlico Sound, North Carolina, is one of the largest estuaries in the continental United States and provides a variety of potential habitats for sharks. In order to identify and spatially delineate shark habitats within Pamlico Sound, shark catch and environmental data were analyzed from the 2007-2014 North Carolina Division of Marine Fisheries (NCDMF) gillnet and longline surveys conducted within the estuary. Principal species were identified and environmental data recorded at survey sites (depth, temperature, salinity, dissolved oxygen, submerged aquatic vegetation (SAV) distance, and inlet distance) were interpolated across Pamlico Sound to create seasonal environmental grids with a 90-m2 cell size. Boosted Regression Tree (BRT) analysis was used to identify the most important environmental factors and ranges associated with presence of each principal species, and the resulting models were used to predict shark capture probability based on the environmental values within the grid cells. The Atlantic Sharpnose Shark (Rhizoprionodon terraenovae), Blacktip Shark (Carcharhinus limbatus), Bull Shark (Carcharhinus leucas), Sandbar Shark (Carcharhinus plumbeus), Smooth Dogfish (Mustelus canis), and Spiny Dogfish (Squalus acanthias) were the principal species in Pamlico Sound. Most species were associated with proximity to the inlet and/or high salinity, and warm temperatures, but the Bull Shark preferred greater inlet distances and the Spiny Dogfish preferred lower temperatures than the other species. Extensive Smooth Dogfish habitat overlap with seagrass beds suggests that seagrass may be a critical part of nursery habitat for this species. Spatial delineation of shark habitat within the estuary will allow for better protection of essential habitat and assessment of potential interactions with other species.

This article explores how Levy's 'Nut Island effect' can be used to help identify health-care teams at risk of becoming isolated, disenchanted and separated physically and psychologically from senior management. Such isolation can lead to disastrous effects.

Objective: Forecast the return on investment (ROI) for advances in biologic therapies in years 2015 and 2030, based upon impact on disease prevalence, morbidity, and mortality for asthma, diabetes, and colorectal cancer., Methods: A deterministic, spreadsheet-based, forecasting model was developed based on trends in demographics and disease epidemiology. 'Return' was defined as reductions in disease burden (prevalence, morbidity, mortality) translated into monetary terms; 'investment' was defined as the incremental costs of biologic therapy advances. Data on disease prevalence, morbidity, mortality, and associated costs were obtained from government survey statistics or published literature. Expected impact of advances in biologic therapies was based on expert opinion. Gains in quality-adjusted life years (QALYs) were valued at $100,000 per QALY., Results: The base case analysis, in which reductions in disease prevalence and mortality predicted by the expert panel are not considered, shows the resulting ROIs remain positive for asthma and diabetes but fall below $1 for colorectal cancer. Analysis involving expert panel predictions indicated positive ROI results for all three diseases at both time points, ranging from $207 for each incremental dollar spent on biologic therapies to treat asthma in 2030, to $4 for each incremental dollar spent on biologic therapies to treat colorectal cancer in 2015. If QALYs are not considered, the resulting ROIs remain positive for all three diseases at both time points., Conclusions: Society may expect substantial returns from investments in innovative biologic therapies. These benefits are most likely to be realized in an environment of appropriate use of new molecules., Limitations: The potential variance between forecasted (from expert opinion) and actual future health outcomes could be significant. Similarly, the forecasted growth in use of biologic therapies relied upon unvalidated market forecasts.

Objective: To describe 2 published pragmatic or practical clinical trials (PCTs) as case studies illustrating successful partnerships between managed care organizations (MCOs) and pharmaceutical manufacturers., Study Design: In today's environment, there is increasing concern about the comparative effectiveness of medical interventions. Various opinion leaders and stakeholders lament the dearth of such evidence and are calling for the public and private sectors to invest up to billions of dollars to create better comparative evidence., Methods: We selected 2 PCTs conducted at different points in the drug life cycle to highlight strengths, limitations, and policy implications. The phase IV study compared fluoxetine hydrochloride vs 2 generic tricyclic antidepressants in selected primary care clinics of a health maintenance organization from 1992 through 1994. The phase IIIb study compared daily budesonide via dry powder inhaler vs triamcinolone acetonide metered-dose inhaler in adult patients with persistent asthma in 25 MCOs from 1995 through 1998., Results: Both PCTs were successfully sponsored and funded by pharmaceutical manufacturers in collaboration with MCOs and provided potentially useful evidence of real-world effectiveness and evidence of value to healthcare decision makers., Conclusions: Industry-sponsored PCTs in managed care are feasible when manufacturer and MCO incentives align and can provide real-world evidence of comparative effectiveness and value for money. These trials can be conducted successfully in the phase IIIb and phase IV environments.

Background: The U.S. workplace injury burden is significant. Our objective was to assess the particular impact of aeroallergen, allergic rhinitis, and antihistamine exposures and side effects on the risk of traumatic work-related injuries, and the associated economic impact., Methods: This is an observational case-control study with 1,223 acute traumatic injury cases that are compared to 1,202 chronic back injury controls. Structured telephone interviews were conducted in 1998 and 1999 on Workers' Compensation applicants injured in 1997. Antihistamine use and pollen levels were measured 2 weeks prior to the injury date., Results: Sedating antihistamine exposures elevated acute injury risk (main effect OR: 2.93). A significant increase in traumatic injury risk was observed for combined sedating antihistamine and high pollen exposures among subjects with physician and self-diagnosed allergic rhinitis (OR: 2.41). Direct medical costs associated with this increased risk were estimated at $143 million in 2001., Conclusions: Workers with physician-diagnosed allergic rhinitis have as high a reliance on sedating antihistamines as do self-diagnosed and self-medicating nasal allergy sufferers. High pollen exposures along with sedating antihistamine use may confer significant additional injury risks among allergic rhinitis sufferers. Medical management "best practices" of diagnosed allergic rhinitis should include avoidance of sedating antihistamines to minimize acute, traumatic injury risks., (Copyright 2003 Wiley-Liss, Inc.)

Background: Divalproex sodium is a mood stabilizer used in the United States for the treatment of acute mania associated with bipolar disorder. Recently, olanzapine, an atypical antipsychotic, was approved for the treatment of acute mania. This study compares the clinical, health-related quality of life (HRQL), and economic outcomes of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder., Method: This 12-week, double-blind, double-dummy, randomized clinical trial included 120 subjects with DSM-IV bipolar disorder type I hospitalized for an acute manic episode recruited from 21 U.S. clinical centers. Subjects were randomly assigned to treatment with either divalproex or olanzapine and were followed in hospital for up to 21 days. If after 21 days clinical improvements (based on the Mania Rating Scale [MRS]) were not observed, subjects were discontinued. Subjects showing clinical improvement were treated for up to 12 weeks. HRQL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) after hospital discharge (baseline) and at 6 and 12 weeks. Medical resource use and costs were collected over the 12-week study., Results: A total of 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomized, and 78 (65%) were followed beyond 21 days. No statistically significant differences between the treatment groups for baseline-to-endpoint MRS or Q-LES-Q scores were observed. Total 12-week outpatient medical costs were significantly lower for the divalproex-treated group (541 US dollars) compared with the olanzapine-treated group (1080 US dollars) (p =.004). There was no significant difference in total medical costs between the 2 groups (divalproex = 13,703 US dollars; olanzapine = 15,180 US dollars; p =.88)., Conclusion: Divalproex is associated with lower 12-week outpatient costs compared with olanzapine. Divalproex and olanzapine have similar short-term effects on clinical or HRQL outcomes in bipolar disorder subjects.

Objective: To examine the relation between blood pressure (BP) control and utilization and cost of healthcare resources., Study Design: A retrospective database study of managed care patients in New Mexico from January 1, 1996, to December 31, 1997., Patients and Methods: We stratified 1000 hypertensive patients into categories based on average and maximum BP. Antihypertensive medication use and cost, number of physician visits, and interval between hypertension-related physician visits were determined., Results: Medication costs increased progressively across all BP categories from lowest to highest, and higher average systolic BP (SBP) was significantly correlated with increased cost (P < .001). There were significant correlations between higher maximum BP and greater number of hypertension-related physician visits (P < .001). Mean number of visits for BP groups was 5.5 for patients with a maximum diastolic BP (DBP) < 85 mm Hg and 10.0 for those with a maximum DBP > or = 100 mm Hg (P < .001). Patients with a maximum SBP > or = 180 mm Hg averaged 9.7 visits, whereas those with a maximum SBP < 120 mm Hg averaged 4.1 visits (P < .001). Both SBP and DBP were significantly correlated with time to next visit (P < .001). Mean visit intervals ranged from 44 days for patients with an SBP < 85 mm Hg to 25 days for those with an SBP > or = 180 mm Hg (P < .001). A similar association was found between DBP and visit interval., Conclusions: Poor control of hypertension is associated with higher drug costs and more physician visits. Aggressive treatment might help reduce managed care costs and resource utilization.