The management of lymph node metastasis from bladder cancer.

AIM: The presence of pelvic lymph node metastasis from bladder cancer has traditionally been associated with a very poor prognosis. The aim of this paper is to review the literature with regard to the management of patients with nodal disease, particularly gross nodal metastasis and suggest a strategy for management of these patients. METHODS: We performed a literature search in the PubMed database and the reference lists of relevant papers describing the management of locally advanced bladder cancer. FINDINGS: There are no randomised studies relating specifically to the management of nodal metastasis in bladder cancer. It is clear however that a significant number of patients with micrometastatic nodal disease may be cured. Few studies exist which address the management of patients with gross nodal disease and consist of series from a limited number of institutions. In patients with gross nodal disease detected pre-operatively or at the time of surgery, a multimodality approach consisting of surgery, chemotherapy and possibly radiotherapy seems appropriate. The prognosis of such patients relates to the pathological stage of the primary tumour and the degree of lymph node involvement. In addition a good response to neoadjuvant chemotherapy may identify patients who are likely to survive longer. CONCLUSIONS: The prognosis for patients with gross nodal disease from bladder cancer is poor although cure may be possible in a small number of patients. In such cases a multimodality approach is appropriate and management decisions should be made on an individual patient basis.     

Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women.

OBJECTIVE: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. METHODS: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus > or = 5 years). RESULTS: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. CONCLUSIONS: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.     

Sexual dysfunction damages: A legal database review

IntroductionProcedural specialties are at higher risk for malpractice claims than non-procedural specialties. Previous studies have examined common damages and malpractice lawsuits resulting from specific procedures. Our goal was to analyze urological interventions that led to sexual dysfunction (SD) claims.MethodsThe Casetext legal research platform was queried using search terms for medical malpractice and common men’s health procedures between 1993 and 2020. In total, 236 cases were found, and 21 cases met the inclusion criteria: malpractice cases against a urologist or urology group, clearly stated legal outcome, and allegation of sexual dysfunction from an intervention that directly caused damages.ResultsA total of 42 damages were cited in 21 lawsuits. The top three damages claimed were erectile dysfunction (ED) (14/42, 33.3%), genital pain syndrome (7/42, 16.7%), and urinary incontinence (5/42, 11.9%). The most commonly cited treatments were urinary catheter placement or removal (3/21, 14.3%), robotic-assisted laparoscopic radical prostatectomy (RALP) (3/21, 14.3%), circumcision (3/21, 14.3%), and penile implant (3/21, 14.3%). In 19 of 21 suits (90.4%), the outcome favored the defendant. Two cases favored the plaintiff: penile implant (failure to prove the patient was permanently, organically impotent prior to the procedure; missed urethral injury at time of surgery, $300 000) and vasectomy (damage to vasculature resulting in loss of testicle, $300 000).ConclusionsMost suspected malpractice cases resulting in SD favored the defendant urologist. Interestingly, urinary catheter placement is as likely to result in litigation as other operative interventions, such as RALP, inflatable penile prosthesis, and circumcision. It is possible that thorough preoperative counselling and increased responsiveness to patients’ postoperative concerns may have avoided litigation in several cases.     

Risk Factors for SARS-CoV-2 Infection and Illness in Cats and Dogs

We tested swab specimens from pets in households in Ontario, Canada, with human COVID-19 cases by quantitative PCR for SARS-CoV-2 and surveyed pet owners for risk factors associated with infection and seropositivity. We tested serum samples for spike protein IgG and IgM in household pets and also in animals from shelters and low-cost neuter clinics. Among household pets, 2% (1/49) of swab specimens from dogs and 7.7% (5/65) from cats were PCR positive, but 41% of dog serum samples and 52% of cat serum samples were positive for SARS-CoV-2 IgG or IgM. The likelihood of SARS-CoV-2 seropositivity in pet samples was higher for cats but not dogs that slept on owners’ beds and for dogs and cats that contracted a new illness. Seropositivity in neuter-clinic samples was 16% (35/221); in shelter samples, 9.3% (7/75). Our findings indicate a high likelihood for pets in households of humans with COVID-19 to seroconvert and become ill.     

Relative efficacy of lasmiditan versus rimegepant and ubrogepant as acute treatments for migraine: network meta-analysis findings

BackgroundIn the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).MethodsData included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II–IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.ResultsAcross 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9–45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.ConclusionsThe efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting.350/350 wordsSupplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01440-w.     

Peripheral Refraction With Toric Orthokeratology and Soft Toric Multifocal Contact Lenses in Myopic Astigmatic Eyes

PurposeThere has been little research on myopia management options for patients with astigmatism. This study quantified changes in peripheral refraction induced by toric orthokeratology (TOK) and soft toric multifocal (STM) contact lenses.MethodsThirty adults with refractive error of plano to −5.00 D (sphere) and −1.25 to −3.50 D (cylinder) were enrolled. Cycloplegic autorefraction was measured centrally, ±20 degrees, and ±30 degrees from the line of sight nasally (N) and temporally (T) on the retina. Measurements were made at baseline, after 10 ± 2 days of TOK wear (without lenses on eye), and after 10 ± 2 days of STM wear (with lenses on the eyes) and compared with repeated-measures analysis of variance.ResultsCompared to baseline, TOK induced a myopic shift in defocus (M) at all locations (all P < 0.01), but STM only induced a myopic shift at 20 T in both eyes and 30 N/T in the left eye (all P < 0.01). TOK resulted in more myopic defocus than STM at all locations (all P < 0.05) except 20 T in the left eye. TOK induced more J₀ astigmatism at all locations (all P < 0.02), except 20 N in the right eye; J₀ with STM was different than baseline at 20 N in both eyes and 30 N in the right eye (all P < 0.02). TOK induced more J₀ astigmatism than STM at all locations (all P < 0.01), except 20 T in the left eye. Differences in J₄₅ astigmatism, when significant, were clinically small.ConclusionsGreater amounts of peripheral myopic defocus and J₀ astigmatism were induced by TOK compared to STM, which may influence efficacy for myopia management.     

The effects of early pregnancy loss on health outcomes and health care utilization and costs

ObjectiveTo evaluate the effects of early pregnancy loss on subsequent health care use and costs.Data SourcesLinked administrative health databases from Manitoba, Canada.Study DesignThis was a population‐based cohort study. The exposure of interest was first recorded ectopic pregnancy or miscarriage (EPM). Outcomes included visits to all ambulatory care providers, family physicians (FPs), specialists, and hospitals, as well as the costs associated with these visits. We also assessed the impact of EPM on a global measure of health service utilization and the incidence and costs of psychotropic medications.Data Collection/Extraction MethodsWe identified women who experienced their first recorded loss (EPM) from 2003–2012 and created a propensity score model to match these women to women who experienced a live birth, with outcome measures available through 31 December 2014. We used a difference in differences approach with multivariable negative binomial models and generalized estimating equations (GEE) to assess the impact of EPM on the aforementioned health care utilization indicators.Principal FindingsEPM was associated with a short‐term increase in visits to, and costs associated with, certain ambulatory care providers. These findings were driven in large part by increased visits/costs to FPs (rate difference [RD]: $19.92 [95% CI: $16.33, $23.51]) and obstetrician‐gynecologists (OB‐GYNs) (RD $9.41 [95% CI: $8.42, $10.40]) in the year immediately following the loss, excluding care associated with the loss itself. We also detected an increase in hospital stays and costs and a decrease in the use of psychotropic medications relative to matched controls.ConclusionPregnancy loss may lead to subsequent increases in certain types of health care utilization. While the absolute costs associated with post‐EPM care are relatively small, the observed patterns of service utilization are informative for providers and policy makers seeking to support women following a loss.     

Cellular Pharmacokinetic Model-Based Analysis of Genistein,Glyceollin, and MK-571 Effects on 5 (and 6)-Carboxy-2′,7′-Dichloroflourescein Disposition in Caco-2 Cells

Pharmacokinetic modeling was used to describe 5 (and 6)-carboxy-2′,7′-dichloroflourescein (CDF) disposition in Caco-2 cells following CDF or CDFDA (CDF diacetate) dosing. CDF transcellular flux was modeled by simple passive diffusion. CDFDA dosing models were based on simultaneous fitting of CDF levels in apical, basolateral, and intracellular compartments. Predicted CDF efflux was 50% higher across the apical versus the basolateral membrane. This difference was similar following apical and basolateral CDFDA dosing, despite intracellular levels being 3-fold higher following basolateral dosing, thus supporting nonsaturable CDF efflux kinetics. A 3-compartment catenary model with intracellular CDFDA hydrolysis described CDF disposition. This model predicted that apical CDF efflux was not altered in the presence of MK-571, and that basolateral membrane clearance was enhanced to account for reduced intracellular CDF in the presence of this multidrug resistance-associated protein (MRP) inhibitor. Similar effects were predicted for glyceollin, while genistein exposure had no predicted effects on CDF efflux. These modulator effects are discussed in the context of model predicted intracellular CDF concentrations relative to reports of CDF affinity (measured by K_m) for MRP2 and MRP3. This model-based analysis confirms the complexity of efflux kinetics and suggests that other transporters may have contributed to CDF efflux.