Cardiovascular risk profile in individuals initiating treatment for overactive bladder - Challenges and learnings for comparative analysis using linked claims and electronic medical record databases.

For managing overactive bladder (OAB), mirabegron, a ß3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011-2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3-1.7) for shingles, 1.5 (CI:0.3-8.2) for hepatitis C, 0.8 (CI:0.4-1.8) and 0.9 (CI:0.6-1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups.

A randomised trial of bevacizumab and reduced light dose photodynamic therapy in age-related macular degeneration: the VIA study.

AIM: To determine if reduced light-dose photodynamic therapy (PDT) combined with bevacizumab will decrease the number of bevacizumab treatments required over 6 months compared with bevacizumab monotherapy in neovascular age-related macular degeneration (AMD). METHODS: Thirty-six patients with neovascular AMD were recruited for this randomised, double-masked, controlled clinical trial. Patients received intravitreal bevacizumab plus PDT using a light dose of either 25 J/cm2 (group 1) or 12 J/cm2 (group 2), or intravitreal bevacizumab plus sham PDT (group 3). Patients returned monthly for possible retreatment with bevacizumab or combination therapy (with a 3-month minimum interval between combination treatments); retreatment decisions were primarily based on optical coherence tomography. The main outcome measure was the mean number of bevacizumab treatments required over 6 months. RESULTS: Patients required a mean of 2.8 bevacizumab treatments in group 1 and 2.5 in group 2, compared with 5.1 in group 3 (p = 0.005 and p<0.001, respectively). CONCLUSIONS: Combination bevacizumab and 25 J/cm2 or 12 J/cm2 PDT significantly reduced the number of bevacizumab treatments required over 6 months. This study was powered to examine number of treatments, but not visual acuities. Nevertheless, visual acuities responded favourably in all three groups. Further studies will be helpful to explore visual outcomes.

Neovascular AMD: an overlooked risk factor for injurious falls.

UNLABELLED: While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls. INTRODUCTION: Impaired vision, particularly peripheral visual function, is a key risk factor for injurious falls. NV-AMD is a leading cause of severely impaired vision among older adults but is associated with a profound central, rather than peripheral, deficit. The objective was to determine whether older women with NV-AMD are at an increased risk of falls or injurious falls. METHODS: We conducted a 12-month prospective cohort study of community-dwelling older (>or=70 years) women, enrolling 114 with NV-AMD and 132 without from a retinal clinic in Vancouver, Canada. Fall incidence was determined through monthly telephone follow-up, with fall severity classified by a blinded reviewer. We compared mean injurious falls per person-year between groups using negative binomial regression. RESULTS: A mean of 0.37 injurious falls per person-year were experienced among NV-AMD participants, compared to 0.16 injurious falls per person-year among non-NV-AMD participants (p = 0.006). The age-adjusted incidence rate ratio for injurious falls, for an individual with NV-AMD compared to without, was 1.77 (1.07-3.02). CONCLUSIONS: Older women with NV-AMD are at almost twice the risk of injurious falls compared to those without. Clinicians caring for older adults should recognise NV-AMD as an important risk factor for injurious falls.

Societal preference values for advanced melanoma health states in the United Kingdom and Australia.

BACKGROUND: No studies measure preference-based utilities in advanced melanoma that capture both intended clinical response and unintended toxicities associated with treatment. METHODS: Using standard gamble, utilities were elicited from 140 respondents in the United Kingdom and Australia for 13 health states. RESULTS: Preferences decreased with reduced treatment responsiveness and with increasing toxicity. CONCLUSIONS: These general population utilities can be incorporated into treatment-specific cost-effectiveness evaluations.

Comparison of visual acuity outcomes in predominantly classic vs occult lesions in age-related macular degeneration treated with photodynamic therapy.

PURPOSE: To determine if patients with occult with no classic and predominantly classic (PC) choroidal neovascular membranes have clinically equivalent visual outcomes after treatment with photodynamic therapy (PDT) with verteporfin. METHODS: This is a retrospective, observational cohort study. Two hundred and seventy-seven consecutive patients with occult or PC choroidal neovascularization secondary to age-related macular degeneration treated with PDT were included. The main outcome was the difference in mean change in Early Treatment of Diabetic Retinopathy Study (ETDRS) acuity lost from baseline in occult vs PC lesions, with the minimal clinically important difference (MCID) set at 7.5 letters. RESULTS: At baseline, 131 patients had occult and 146 had PC choroidal neovascularization. Twelve-month follow-up data were available for 94 occult and 110 PC participants. Occult patients lost an average of 8.7 letters (1.9 lines), and patients in the PC group an average of 10.0 ETDRS letters (two lines) over 12 months. The mean letters lost at 12 months was not significantly different between the groups, and the MCID was not detected (difference=1.3 letters; P=0.411; 95% confidence interval (-2.3, 5.6)). Patients with occult lesions required a mean of 2.99 treatments vs a mean of 2.96 treatments in the PC group (out of a possible 4; P=0.172). CONCLUSION: We were not able to detect a clinically important difference in mean change in visual acuity with PDT treatment between patients with occult and PC lesions.

Characteristics of two cases with dup(15)(q11.2-q12): one of maternal and one of paternal origin.

PURPOSE: The phenotype correlations for interstitial duplications that include the Prader-Willi/Angelman syndrome critical region are not well established. We describe two such duplication cases, one of which was of maternal origin and the other was paternal. METHODS: High resolution G-banding, fluorescence in situ hybridization (FISH) for SNRP-N and D15S10 were used for cytogenetic analysis. Southern blot analyses based on parent of origin specific DNA methylation at D15S63 (PW71) locus were utilized for detection of methylated and unmethylated fragments. RESULTS: The duplication was established by the FISH analysis. The molecular pattern suggested a maternal origin of the duplication in patient 1 and a paternal origin in patient 2. Patient 1 (2 years old) had developmental and speech delays with pervasive developmental disorder or mild autism, strabismus, and normal growth parameters with seizures. Patient 2 (16 years old) had global developmental delay, verbal IQ of 94, depression, obesity, food-seeking behavior, and significant behavioral problems that included self-injurious tendencies. Neither patient had significant dysmorphic features or abnormalities of internal organs. CONCLUSION: The two cases suggest that some patients with 15q11.2q12 duplication may have significant anomalies, and there appear to be phenotypic differences between maternal and paternal transmission of the duplication.

Thyroiditis. Differentiation of acute suppurative and subacute. Case report and review of the literature.

Acute suppurative thyroiditis is rarely seen during childhood. The classic clinical features of this illness (fever, neck pain, and a swollen, tender mass over the thyroid gland) can differentiate acute thyroiditis from the more common subacute thyroiditis. In less typical cases, however, this distinction can be difficult. An adolescent male presented with a swollen, tender thyroid gland. Atypical laboratory findings and the lack of fever and toxicity delayed the diagnosis and treatment of acute suppurative thyroiditis. A review of the pediatric literature summarizes clinical and diagnostic features valuable in the differential between acute suppurative thyroiditis and subacute thyroiditis in childhood. The important contribution of fistulae between the piriform sinus and thyroid gland to the pathogenesis and acute suppurative thyroiditis is emphasized. Such a fistula should be sought in every patient in whom this entity is diagnosed.

New spectrophotometric and radiochemical assays for acetyl-CoA: arylamine N-acetyltransferase applicable to a variety of arylamines.

Simple and sensitive spectrophotometric and radiochemical procedures are described for the assay of acetyl-CoA:arylamine N-acetyltransferase (NAT; EC 2.3.1.5), which catalyzes the reaction acetyl-CoA + arylamine----N-acetylated arylamine + CoASH. The methods are applicable to crude tissue homogenates and blood lysates. The spectrophotometric assay is characterized by two features: (i) NAT activity is measured by quantifying the disappearance of the arylamine substrate as reflected by decreasing Schiff's base formation with dimethylaminobenzaldehyde. (ii) During the enzymatic reaction, the inhibitory product CoASH is recycled by the system acetyl phosphate/phosphotransacetylase to the substrate acetyl-CoA. The radiochemical procedure depends on enzymatic synthesis of [3H]acetyl-CoA in the assay using [3H]acetate, ATP, CoASH, and acetyl-CoA synthetase. NAT activity is measured by quantifying N-[3H]acetylarylamine after separation from [3H]acetate by extraction. Product inhibition by CoASH is prevented in this system by the use of acetyl-CoA synthetase.

Biodistribution of a new lipid-soluble CT contrast agent. Evaluation of cholesteryl iopanoate in the rabbit.

Cholesteryl iopanoate, the prototype for a new class of lipid-soluble, site-specific contrast agents, has undergone preliminary evaluation for organic-specific uptake. This report describes the tissue distribution profile of this radioiodinated sterol ester in the rabbit as a function of time following intravenous injection of tracer doses. Selective accumulation of this agent in the liver and adrenal was observed relative to blood and other tissues. Maximum contrast concentration was achieved between 24 and 48 hours postinjection. Analysis of lipid extra of liver, adrenal, and plasma indicated that the compound was relatively resistant to hydrolysis and dehalogenation. The hepatic selectivity and retention of cholesteryl iopanoate support further study of this or related agents for site-specific, contrast-enhanced computed tomography.

Potential tumor- or organ-imaging agents. 23. Sterol esters of iopanoic acid.

A series of sterol esters of iopanoic acid was synthesized and evaluated for their potential to selectively localize in liver and steroid-secreting tissues for possible application in either computed tomography or nuclear medicine imaging. Unlike free iopanoic acid (1), which was rapidly cleared following intravenous administration to rats, cholesteryl iopanoate (2) was found to accumulate in liver, adrenal cortex, and ovary. At 24 h, the ovary was found to contain the highest concentration of 2. The ability of 2 to accumulate in the above tissues was attributed to its resistance to hydrolysis. Pregnenolone iopanoate (3) and dehydroepiandrosterone iopanoate (4), on the other hand, were shown to reach unusually high concentrations in the adrenal cortex within 0.5 h of administration but declined to much lower levels by 24 h. Lipid extraction of tissues showed 3 and 4 to be susceptible to in vivo hydrolysis, which undoubtedly was a major factor in their clearance from adrenal tissue.