Zinc Binding Inhibits Cellular Uptake and Antifungal Activity of Histatin-5 in Candida albicans.

Histatin-5 (Hist-5) is a polycationic, histidine-rich antimicrobial peptide with potent antifungal activity against the opportunistic fungal pathogen Candida albicans. Hist-5 can bind metals in vitro, and metals have been shown to alter the fungicidal activity of the peptide. Previous reports on the effect of Zn2+ on Hist-5 activity have been varied and seemingly contradictory. Here, we present data elucidating the dynamic role Zn2+ plays as an inhibitory switch to regulate Hist-5 fungicidal activity. A novel fluorescently labeled Hist-5 peptide (Hist-5*) was developed to visualize changes in internalization and localization of the peptide as a function of metal availability in the growth medium. Hist-5* was verified for use as a model peptide and retained antifungal activity and mode of action similar to native Hist-5. Cellular growth assays showed that Zn2+ had a concentration-dependent inhibitory effect on Hist-5 antifungal activity. Imaging by confocal microscopy revealed that equimolar concentrations of Zn2+ kept the peptide localized along the cell periphery rather than internalizing, thus preventing cytotoxicity and membrane disruption. However, the Zn-induced decrease in Hist-5 activity and uptake was rescued by decreasing the Zn2+ availability upon addition of a metal chelator EDTA or S100A12, a Zn-binding protein involved in the innate immune response. These results lead us to suggest a model wherein commensal C. albicans may exist in harmony with Hist-5 at concentrations of Zn2+ that inhibit peptide internalization and antifungal activity. Activation of host immune processes that initiate Zn-sequestering mechanisms of nutritional immunity could trigger Hist-5 internalization and cell killing.

The humanistic burden of myasthenia gravis: A systematic literature review.

BACKGROUND/OBJECTIVES: While the clinical manifestations of myasthenia gravis (MG) are well understood, its humanistic impact is not. The objective of this systematic literature review (SLR) was to provide a comprehensive understanding of the humanistic burden of MG with regards to psychological symptoms and health-related quality of life (HRQoL) according to patients and caregivers. METHODS: A systematic search was conducted on December 27, 2019, in MEDLINE and Embase to identify English-language studies that were published from January 1, 2009-December 27, 2019 and presented relevant information on the humanistic burden among adults with MG and their caregivers. Title/abstract and full-text screening was performed by two investigators, with any discrepancies resolved by a third investigator. RESULTS: Sixty-seven publications were included in the SLR. Compared with the general population, patients with MG experienced worse HRQoL. Studies reporting on psychological symptoms of MG, including depression, anxiety, fatigue, and sleep, were heterogeneous in terms of the scales and instruments used to assess patients, as well as the patient populations themselves. However, in general those with more severe symptoms and hospitalization days had worse depression and anxiety, and fatigue and sleep improved with disease remission and/or improvement. Scores were worse for females compared with males and where evaluated, HRQoL scores generally improved following treatment. CONCLUSION: While the literature demonstrates that symptoms associated with MG get better with disease improvement and remission, additional options in efficacious therapy that adequately address the disease-related symptoms and also improve HRQoL may contribute to beneficial outcomes in a greater number of patients with MG.

Economic and Clinical Burden Associated With Intensification of Glaucoma Topical Therapy: A US Claims-based Analysis.

PRECIS: Incremental addition of intraocular pressure-lowering topical drops is associated with shorter-lasting benefit and higher health-related costs with each additional agent, suggesting a need for new treatment options to improve disease control and reduce treatment burden. PURPOSE: The purpose of this study was to evaluate treatment intensification as a driver of clinical and economic burden in patients receiving topical glaucoma medications for open-angle glaucoma/ocular hypertension. METHODS: This retrospective analysis of administrative claims data (January 2011 to July 2017) from the IQVIA PharMetrics Plus database included diagnosed patients who initiated or intensified treatment with 1 to 4 topical glaucoma medications of a different drug class between January 2012 and July 2015 (index date being the first such event during this period). Patients with prior open-angle glaucoma surgery or an equal or greater number of topical glaucoma medication classes during the preindex period were excluded. Treatment intensification rates and eye-related outpatient costs were assessed over 24 months postindex. RESULTS: Of 48,402 patients (mean age: 61.4 y), 22,874 (47.3%), 16,214 (33.5%), 7137 (14.7%), and 2177 (4.5%) received a first, second, third, or fourth medication class, respectively, as their first observed initial or intensified regimen. Among cohorts receiving 1, 2, 3, or 4 medication classes, 7.8%, 12.2%, 17.2%, and 22.6% of patients and 12.6%, 18.5%, 25.9%, and 33.7% of patients had subsequent treatment augmentation (class addition or glaucoma procedure, laser or surgical) within 12 and 24 months postindex, respectively. Eye-related outpatient costs over 24 months increased with each additional topical glaucoma medication class at index [mean (SD): $1610 ($3460), $2418 ($4863), $2872 ($5110), and $3751 ($6608) in the 1, 2, 3, or 4 class cohorts, respectively]. CONCLUSION: Multiple-drop therapies yielded shorter-lasting benefits with each additional agent and were associated with the increased clinical and economic burden.

Safe and effective use of phototherapy and photochemotherapy in the treatment of psoriasis.

Psoriasis is a chronic, multisystem inflammatory disease, predominantly affecting the skin and joints, which is present in 2-3% of the world's population. Narrow band ultraviolet B (NB-UVB) and Psoralen + ultraviolet A (PUVA) are recognised, effective and, in the case of UVB, economical second-line treatments for psoriasis where topical therapies fail to control the disease or are an impracticable option due to the extent of skin involvement. This article examines the history of phototherapy and photochemotherapy and looks at current phototherapy treatments used for psoriasis. It discusses side effects of treatment and regimens that can be followed to increase effectiveness of treatment and minimise risks. The role of the nurse phototherapist is also discussed.

Management and Outcomes for Neovascular Age-Related Macular Degeneration: Analysis of United States Electronic Health Records.

PURPOSE: To assess anti-vascular endothelial growth factor (VEGF) management patterns and anatomic and visual acuity (VA) outcomes among patients with neovascular age-related macular degeneration (nAMD) in United States clinical practice. DESIGN: Retrospective observational cohort study. PARTICIPANTS: Patients (N = 30 106) initiating intravitreal anti-VEGF treatment for nAMD between October 2009 and November 2016. METHODS: Analysis of longitudinal electronic health records from USRetina. MAIN OUTCOME MEASURES: Number of intravitreal injections, OCT examinations, and fluorescein angiography (FA) examinations per study eye during the first 12 months; corrected VA and central retinal thickness (CRT) at 12 months; and number of ophthalmologist visits, stratified by index anti-VEGF agent. RESULTS: Over the first 12 months, patients made a mean of 8.1 (range, 1-39) ophthalmologist visits, received a mean of 6.0 (range, 1-27) anti-VEGF injections, and underwent 7.2 OCT and 5.3 FA examinations per study eye. For eyes with paired baseline and 12-month readings, mean CRT declined from 320 to 271 µm (mean change, -48 µm), and mean VA increased from 60.3 to 61.0 approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letters (mean change, +0.6 letters). Twelve months after initiating index treatment with bevacizumab, ranibizumab, and aflibercept, 19.3%, 15.8%, and 15.5% of eyes, respectively, showed greater than 10-letter gain, whereas 13.2%, 14.7%, and 14.4% of eyes, respectively, showed greater than 10-letter loss. Mean change from baseline VA at 12 months increased linearly with cumulative anti-VEGF injection count: +1.79 versus -0.95 approximate ETDRS letters for eyes receiving 7 or more injections versus fewer than 7 injections. Similarly, the magnitude of the reduction from baseline CRT at 12 months tended to increase linearly with increasing number of anti-VEGF injections. Multivariate linear regression analysis, adjusted for covariates, indicated a significant association between cumulative number of anti-VEGF injections and change from baseline in VA at 12 months, with each unit increase producing an estimated gain of 0.37 approximate ETDRS letters. CONCLUSIONS: This analysis of combined morphologic and functional outcomes of anti-VEGF therapy, the largest conducted to date in nAMD, identified relatively low anti-VEGF injection frequencies, coupled with moderate anatomic and limited VA improvements, in United States clinical practice.

Structural and Spectroscopic Investigation of Two Plutonium Mellitates.

The aqueous reaction of mellitic acid (H6mell) with 242PuBr3·nH2O forms two plutonium mellitates, 242Pu2(mell)(H2O)9·H2O (Pu-1α) and 242Pu2(mell)(H2O)8·2H2O (Pu-1ß). These compounds are compared to the isomorphous lanthanide mellitates with similar ionic radii via bond length analysis. Both plutonium compounds form three-dimensional metal-organic frameworks, with Pu-1α having two unique metal centers and Pu-1ß having one. All plutonium metal centers exhibit nine-coordinate geometries. Our results show metal-oxygen bond lengths for plutonium significantly shorter than those of the previously reported lanthanum and herein reported cerium analogues, consistent with the nine-coordinate ionic radii. Clear Laporte-forbidden 5f → 5f transitions are observed in the ultraviolet-visible-near-infrared spectra and are assigned to trivalent plutonium. However, there is a distinct color difference between the two plutonium compounds.

Real-World Outcomes of Selective Laser Trabeculoplasty in the United Kingdom.

PURPOSE: Selective laser trabeculoplasty (SLT) is a common treatment option for managing glaucoma and ocular hypertension. We assessed the real-world effectiveness of SLT and baseline factors associated with treatment success in the United Kingdom. DESIGN: Retrospective observational study of de-identified electronic medical records (Medisoft Glaucoma module [Medisoft Ltd, Leeds, UK]) from 5 UK ophthalmology teaching centers. PARTICIPANTS: Adult patients undergoing their first recorded SLT. For bilateral SLT (same day), analyses included 1 randomly selected eye. METHODS: Patient demographics, procedure details, and clinical outcomes data were extracted. Factors associated with treatment success were assessed using multivariable Cox regression. MAIN OUTCOME MEASURES: Change from baseline in intraocular pressure (IOP) and glaucoma medication use at 12 to 18 and 24 to 36 months post-SLT. A Kaplan-Meier survival analysis was also conducted. Failure of SLT was defined as any further glaucoma procedure post-SLT or any of the following at 2 consecutive visits: IOP >21 mmHg, IOP reduction <20% from baseline, or increase in glaucoma medications from baseline. RESULTS: A total of 831 SLT-treated eyes (mean baseline IOP 22.0 mmHg) of 831 patients were analyzed. At 12 to 18 and 24 to 36 months post-SLT, respectively, significant reductions in IOP (-4.2 [95% confidence interval {CI}, -4.7 to -3.7] and -3.4 [95% CI, -4.1 to -2.7] mmHg; both P < 0.0001) and significant increases in the number of glaucoma medications (0.13 [95% CI, 0.04-0.23], P = 0.007, and 0.20 [95% CI, 0.06-0.33], P = 0.005) were observed. Survival analysis demonstrated treatment success in 70%, 45%, and 27% of eyes at 6, 12, and 24 months post-SLT, respectively. Higher baseline IOP was strongly associated with treatment success (hazard ratio [HR], 0.67 for baseline IOP >21 mmHg vs. ≤21 mmHg, 95% CI, 0.57-0.80; P < 0.001). Selective laser trabeculoplasty success was not significantly associated with age (P = 0.78), baseline visual field mean deviation (P = 1.00), or concurrent use of IOP-lowering medication (P = 0.52). CONCLUSIONS: Most patients initially responded to SLT, but the majority failed within 1 year. Efficacy of SLT was better in patients with higher baseline IOP but did not differ by glaucoma severity or concurrent use of IOP-lowering medication. These findings may help inform which patients are suitable for SLT therapy.

Relationship between duration and extent of oedema and visual acuity outcome with ranibizumab in diabetic macular oedema: A post hoc analysis of Protocol I data.

BACKGROUND/OBJECTIVES: This post hoc analysis explores the relationship between residual oedema exposure after ranibizumab treatment initiation and long-term visual acuity outcome in eyes with centre-involved diabetic macular oedema (DMO). SUBJECTS/METHODS: Eyes randomised to the ranibizumab + prompt or deferred laser treatment arms in the Protocol I trial and with observed central retinal thickness (CRT) readings at baseline and ≥1 follow-up visits (n = 367) were stratified by 1) oedema duration (number of study visits with CRT ≥ 250 µm during the first 52 weeks of ranibizumab treatment); and 2) oedema extent (amount of excess CRT [≥ 250 µm] at each study visit, averaged over the first 52 weeks). Associations between measures of residual oedema and best-corrected visual acuity (BCVA) were assessed in multiple regression analyses. RESULTS: Oedema duration and oedema extent during the first 52 weeks of ranibizumab treatment showed significant negative associations with BCVA improvement at weeks 52, 104 and 156. Eyes with the most persistent oedema gained (mean) 4.4 (95% CI 0.1─8.7) fewer Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 156 than eyes with the least persistent oedema (P = 0.044). Eyes with the greatest amount of oedema gained (mean) 9.3 (95% CI 4.0─14.5) fewer ETDRS letters at week 156 than eyes with the least amount of oedema (P < 0.001). CONCLUSIONS: Macular oedema exposure over the first 52 weeks of ranibizumab treatment is a negative prognostic factor for long-term visual acuity improvement in centre-involved DMO.

ASSOCIATION BETWEEN EARLY ANATOMIC RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY AND LONG-TERM OUTCOME IN DIABETIC MACULAR EDEMA: An Independent Analysis of Protocol i Study Data.

PURPOSE: This post hoc analysis explores the relationship between early retinal anatomical response and long-term anatomical and visual outcomes with ranibizumab in center-involved diabetic macular edema. METHODS: Eyes randomized to the ranibizumab plus prompt laser and ranibizumab plus deferred laser treatment arms in the Protocol I study were categorized according to their proportional reduction (<20 vs. ≥20%) in central retinal thickness (CRT) after 12 weeks. Adjusted and unadjusted analyses assessed the association between early (Week 12) anatomical response and long-term (Weeks 52 and 156) anatomical and best-corrected visual acuity outcomes. RESULTS: Of 335 study eyes, 118 showed limited (<20%) and 217 showed strong (≥20%) CRT reduction at Week 12. In unadjusted and adjusted analyses, limited early CRT response was negatively and significantly associated with strong CRT response at Weeks 52 and 156. Sensitivity analyses indicated that this association was robust and unrelated to any "floor effect." In unadjusted analyses, a strong early CRT response was associated with greater long-term improvement in best-corrected visual acuity; after controlling for confounders, the association lost statistical significance. CONCLUSION: Early CRT response to ranibizumab is a significant prognostic indicator of medium- to long-term anatomical outcome in center-involved diabetic macular edema.

Vision Outcomes Following Anti-Vascular Endothelial Growth Factor Treatment of Diabetic Macular Edema in Clinical Practice.

PURPOSE: To determine monitoring and treatment patterns and vision outcomes in real-world patients initiating anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME). DESIGN: Retrospective interventional cohort study. METHODS: Setting: Electronic medical record analysis of Geisinger Health System data. STUDY POPULATION: A total of 110 patients (121 study eyes) initiating intravitreal ranibizumab or bevacizumab for DME during January 2007‒May 2012, with baseline corrected visual acuity of 20/40 to 20/320, and ≥1 ophthalmologist visit during follow-up. MAIN OUTCOME MEASURES: Intravitreal injections per study eye during the first 12 months; corrected visual acuity, change in corrected visual acuity from baseline, proportions of eyes with ≥10 or ≥15 approximate Early Treatment Diabetic Retinopathy Study letter gain/loss at 12 months; number of ophthalmologist visits. RESULTS: Over 12 months, mean number of ophthalmologist visits was 9.2; mean number of intravitreal injections was 3.1 (range, 1-12), with most eyes (68.6%) receiving ≤3 injections. At 12 months, mean corrected visual acuity change was +4.7 letters (mean 56.9 letters at baseline); proportions of eyes gaining ≥10 or ≥15 letters were 31.4% and 24.0%, respectively; proportions of eyes losing ≥10 or ≥15 letters were 10.8% and 8.3%, respectively. Eyes receiving adjunctive laser during the first 6 months (n = 33) showed similar change in corrected visual acuity to non-laser-treated eyes (n = 88) (+3.1 vs +5.3 letters at 12 months). CONCLUSIONS: DME patients receiving anti-VEGF therapy in clinical practice undergo less frequent monitoring and intravitreal injections, and achieve inferior vision outcomes to patients in landmark clinical trials.

TREATMENT PATTERNS AND 2-YEAR VISION OUTCOMES WITH BEVACIZUMAB IN DIABETIC MACULAR EDEMA: An Analysis From a Large U.S. Integrated Health Care System.

PURPOSE: To assess health care utilization and vision outcomes over 2 years in patients receiving bevacizumab treatment in clinical practice for diabetic macular edema. METHODS: Patients with newly diagnosed diabetic macular edema who received an intravitreal bevacizumab injection within 12 months of initial diagnosis were identified from Kaiser Permanente's 350,000 patients with diabetes mellitus treated between 2008 and 2013. Snellen best-corrected visual acuity (BCVA), number of intravitreal injections, and patient characteristics were abstracted from the electronic record. The main outcome measure was change in BCVA. RESULTS: Three hundred and nine patients met the inclusion criteria and had 2 years of follow-up after their first bevacizumab injection. These patients had a mean of 3.1 injections (range, 1-17) during the 2-year follow-up. Mean BCVA improvement was 5.4 letters at 12 months and 5.3 letters at 24 months. Only 29.8% of patients demonstrated ≥3 lines of vision improvement from baseline, whereas 12.3% had ≥3 lines of vision loss from baseline at 24 months. CONCLUSION: This is the largest U.S. clinical practice-based study of bevacizumab use in diabetic macular edema. Consistent with national studies, the frequency of injection was low. Average BCVA improvement was lower than in anti-vascular endothelial growth factor trials. Significant BCVA improvement was achieved in approximately 30% of patients with newly diagnosed diabetic macular edema.

Azacitidine for Treating Acute Myeloid Leukaemia with More Than 30 % Bone Marrow Blasts: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE. The clinical effectiveness data used in the company's economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: "Remission", "Non-remission", "Relapse/Progressive disease" and "Death". The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine compared with the CCR was £20,648 per quality-adjusted life-year (QALY) gained. In the probabilistic sensitivity analysis, the mean ICER was £17,423 per QALY. At the willingness-to-pay of £20,000, £30,000 and £50,000 per QALY, the probability of azacitidine being cost effective was 0.699, 0.908 and 0.996, respectively. The ERG identified a number of errors in Celgene's model and concluded that the results of the company's economic evaluation could not be considered robust. After amendments to Celgene's model, the base-case ICER was £273,308 per QALY gained. In the probabilistic sensitivity analysis, the mean ICER was £277,123 per QALY. At a willingness-to-pay of £100,000 per QALY, the probability of azacitidine being cost effective was less than 5 %. In all exploratory analyses conducted by the ERG, the ICER exceeded the NICE's cost-effectiveness threshold range of £20,000-30,000 per QALY. Given the evidence provided in the submission, azacitidine did not fulfil NICE's end-of-life criteria. After considering the analyses performed by the ERG and submissions from clinician and patient experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.

Early and Long-Term Responses to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I Data.

PURPOSE: To determine whether early visual acuity response to ranibizumab in diabetic macular edema is associated with long-term outcome. DESIGN: Post hoc analysis of randomized controlled trial data. METHODS: Pooled data from the ranibizumab plus prompt and deferred laser treatment arms of the Diabetic Retinopathy Clinical Research Network's Protocol I study were used to explore the relationship between early (week 12) and late (weeks 52-156) visual acuity response (mean change from baseline in best-corrected visual acuity [CFB BCVA]; categorized improvement [<5, 5-9, or ≥10 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] in BCVA). RESULTS: In the analysis population (340 eyes), <5-, 5- to 9-, and ≥10-letter BCVA improvements occurred in 39.7%, 23.2%, and 37.1% of eyes, respectively, at 12 weeks, and 34.2%, 16.5%, and 49.3% of eyes at 156 weeks. Within each early BCVA response category (<5, 5-9, and ≥10 letters of improvement at 12 weeks), mean CFB BCVA at 52-156 weeks varied by <5 letters from that at 12 weeks. CFB BCVA and <5-letter improvement at 12 weeks showed significant positive and negative association, respectively, with CFB BCVA and ≥10-letter improvement at 52 and 156 weeks. Similar relationships were demonstrated in eyes with baseline BCVA <69 letters, and associations remained significant after multivariate adjustment for potential confounders. CONCLUSIONS: Ranibizumab ± laser therapy resulted in similar rates (∼40%) of suboptimal (<5-letter) and pronounced (≥10-letter) BCVA improvement at 12 weeks. Eyes with suboptimal early BCVA response showed poorer long-term visual outcomes than eyes with pronounced early response (mean improvement 3.0 vs 13.8 letters at 156 weeks).

Comorbidity and Health Care Resource Use Among Commercially Insured Non-Elderly Patients With Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: Diabetic macular edema (DME) is a leading cause of blindness for non-elderly adults; however, health care-associated burden data from this population is lacking. The authors describe health care-associated burden in non-elderly patients with DME compared to those with diabetes and no DME. PATIENTS AND METHODS: In this retrospective, large-cohort study examines enrollment and health care claims (2007 to 2011) from a national database of insured patients aged 18 to 63 years (mean: 51). Comorbidity and health care utilization differences between patients with DME (n = 24,326) and matched controls with diabetes but no DME (n = 122,710) were analyzed over 1 and 3 years. RESULTS: DME patients had significantly more baseline comorbidities, and generally developed them at a higher rate over the study. Health care resource utilization rates were significantly higher in DME patients for every category analyzed. Patients with DME averaged more than 10 health care visits more than those with diabetes but no DME (25.5 vs 14.9; P < .001). CONCLUSION: Working-age patients with DME exhibit a complicated comorbidity profile and high associated burden of health care consumption. Considering this burden is critical for managing this complex population.

Clinical monitoring of patients with age-related macular degeneration treated with intravitreal bevacizumab or ranibizumab.

BACKGROUND AND OBJECTIVE: Patients with neovascular age-related macular degeneration (AMD) require frequent follow-up and regular anti-VEGF injections for optimal outcomes. Although studies suggest that injection frequency is suboptimal in clinical practice, monitoring frequency in this setting is unclear. This study evaluates annual monitoring patterns between 2008 and 2011. PATIENTS AND METHODS: This retrospective claims analysis included newly diagnosed neovascular AMD patients with at least one intravitreal bevacizumab or ranibizumab injection (8,811 and 2,877 patients, respectively). Patient monitoring and treatment patterns were assessed at 12-month intervals. RESULTS: From 2008 to 2010, the mean number of injections increased. In the 2010 cohort, among bevacizumab- and ranibizumab-treated patients, respectively, less than 23% and less than 40% had at least 10 ophthalmologist visits, and less than 4% and less than 21% had at least 10 optical coherence tomography scans. CONCLUSION: Patients with neovascular AMD in clinical settings during 2008 to 2011 were monitored less frequently and received fewer anti-VEGF injections than patients in major clinical trials, which may affect outcomes.

Cost-effectiveness of laparoscopic gastric banding and bypass for morbid obesity.

OBJECTIVE: To assess the cost-effectiveness of laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB) as treatment for morbid obesity. STUDY DESIGN: A Markov model was developed to simulate weight loss, health consequences, and costs for surgical treatment of morbid obesity. The model was used to estimate incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life-year (QALY) gained. METHODS: Estimates of procedure effectiveness were derived from published results of a head-to-head randomized controlled trial. Other model parameters, including complication rates, costs of treatment, adverse events and obesity, mortality rates, and utilities, were estimated from published literature and publicly available databases. Costs (2006 US dollars) and QALYs were discounted by 3% per annum. RESULTS: Under conservative assumptions, both LAGB and LRYGB improved health outcomes, at a higher cost, compared with no treatment. ICERs for both LAGB and LRYGB versus no treatment were below $25,000 per QALY gained. ICERs were lower for individuals with higher initial body mass index and higher for older individuals. ICERs for men were generally higher than those of women. Sensitivity analyses showed these results to be robust to reasonable variation in model parameters and overall parameter uncertainty. Base-case ICERs for LRYGB versus LAGB were below $25,000 per QALY gained, but were highly sensitive to model assumptions. CONCLUSION: Both LAGB and LRYGB provide significant weight loss and are cost-effective compared with no treatment at conventionally accepted thresholds for medical interventions.