Bilateral Craniofacial Cleft (Tessier Type 4): Case Report and Oculoplastic Reconstruction.

Bilateral Tessier type 4 craniofacial clefts are extremely rare and disfiguring malformations with vision-threatening ramifications. To date, there is no consensus in the literature with respect to the ideal surgical technique and management of these patients. Emergent eyelid reconstruction and additional procedures may be required to protect the cornea and avoid further ophthalmic and surgical complications. We present our experience and challenges of managing a case of bilateral Tessier type 4 clefting with an emphasis on oculoplastic considerations.

Cost-effectiveness of Hepatitis B Virus Infection Screening and Treatment or Vaccination in 6 High-risk Populations in the United States.

BACKGROUND: Two million individuals with chronic hepatitis B (CHB) in the United States are at risk for premature death due to liver cancer and cirrhosis. CHB can be prevented by vaccination and controlled with treatment. METHODS: We created a lifetime Markov model to estimate the cost-effectiveness of strategies to prevent or treat CHB in 6 high-risk populations: foreign-born Asian/Pacific Islanders (API), Africa-born blacks (AbB), incarcerated, refugees, persons who inject drugs (PWID), and men who have sex with men (MSM). We studied 3 strategies: (a) screen for HBV infection and treat infected ("treatment only"), (b) screen for HBV susceptibility and vaccinate susceptible ("vaccination only"), and (c) screen for both and follow-up appropriately ("inclusive"). Outcomes were expressed in incremental cost-effectiveness ratios (ICERs), clinical outcomes, and new infections. RESULTS: Vaccination-only and treatment-only strategies had ICERs of $6000-$21 000 per quality-adjusted life-year (QALY) gained, respectively. The inclusive strategy added minimal cost with substantial clinical benefit, with the following costs per QALY gained vs no intervention: incarcerated $3203, PWID $8514, MSM $10 954, AbB $17 089, refugees $17 432, and API $18 009. Clinical complications dropped in the short/intermediate (1%-25%) and long (0.4%-16%) term. Findings were sensitive to age, discount rate, health state utility in immune or susceptible stages, progression rate to cirrhosis or inactive disease, and tenofovir cost. The probability of an inclusive program costing <$50 000 per QALY gained varied between 61% and 97% by population. CONCLUSIONS: An inclusive strategy to screen and treat or vaccinate is cost-effective in reducing the burden of hepatitis B virus among all 6 high-risk, high-prevalence populations.

Isolated cranio-orbitofacial neurofibroma mimicking vascular malformation.

Isolated neurofibromas in the absence of systemic neurofibromatosis are known as solitary or localized neurofibromas. When present in the orbit, these lesions may appear clinically and radiographically similar to other tumors, complicating diagnosis and management. Key radiographic signs may guide clinicians to the correct diagnosis when the presentation and patient demographic data obfuscate the disease entity. We present a case of a large multi-lobulated neurofibroma misdiagnosed as a lymphangioma. A brief review of these tumors emphasizing key radiographic features is also included.

Scleral Contact Lenses in an Academic Oculoplastics Clinic: Epidemiology and Emerging Considerations.

PURPOSE: To describe the role and efficacy of scleral contact lenses (SCLs) in the treatment of progressive keratopathy in patients who have undergone periocular surgical procedures, to investigate the financial impact of these surgical interventions, and to demonstrate the role of oculoplastic surgery in improving scleral contact lens fit. METHODS: A retrospective medical record review was performed to identify patients who both received SCLs and were examined by the oculoplastics service at the University of Iowa between January 1990 and December 2015. Inclusion criteria also required a minimum of 12 months of patient follow up after being fit with a SCL. The indication for SCL use, as well as clinical outcomes and cumulative relative value units (RVUs) of prior oculoplastic treatments and SCL therapy were recorded for each patient. RESULTS: Six hundred and fifty-nine patients were fitted with SCLs at the authors' institution during the 25-year study period, 43 of whom were examined by the oculoplastics service for reasons related to their SCL. Patients who were fitted for SCLs before (27 patients) or after (16 patients) evaluation in the oculoplastics clinic presented with a variety of corneal and periocular pathology. Corneal indications for SCLs in patients seen secondarily in the oculoplastics clinic included decreased corneal sensation (from CN V palsy or neurotrophic keratopathy), decreased corneal healing from limbal stem cell deficiency, exposure keratopathy, and keratoconjunctivitis sicca secondary to Sjogren's syndrome or orbital radiation. Indications for oculoplastic clinic evaluation in current scleral lens patients included lagophthalmos, trichiasis, epiphora, cicatricial changes in the eyelids or fornices, and eyelid or eyebrow malposition affecting SCL centration. In all 27 patients, surgical intervention resulted in improved SCL centration. Sixteen patients (5 with CN VII palsy, 4 with CN V and CN VII palsy, 4 with neurotrophic keratitis, and 3 with cicatricial entropion) had progressive corneal decompensation despite primary oculoplastics procedures to protect the cornea and ultimately benefitted from SCL treatment secondarily. Fourteen of these 16 patients demonstrated an improved visual acuity of 1 line or more using SCLs. Procedures performed before referral for SCLs included tarsorrhaphies, gold weights, ectropion repair with lateral tarsal strip, retraction repair with spacer grafts, full-thickness skin grafts, cheek lifts, and punctal occlusion. The total RVUs of these procedures performed per patient were tabulated. The RVU range was 10.47-33.96 with an average of 19.5 RVUs (standard deviation = 9.4 RVUs) per patient. CONCLUSIONS: Scleral contact lenses may offer a useful alternative to stabilize the ocular surface, improve vision, and minimize the financial impact and morbidity of multiple periocular procedures in select patients with progressive keratopathy of varying etiologies. The therapeutic indications and utilization of SCLs are likely to increase in oculoplastic practices with optometric support, particularly in academic settings. Surgical correction of eyelid and eyebrow malposition, as well as epiphora, may also be useful adjunctive procedures to optimize SCL fit.

Orbital Mucormycosis Following Periorbital Cutaneous Infection.

Mucormycosis is an aggressive fungal infection characterized by rapidly progressive angioinvasion and tissue necrosis. When present in the orbit, mucormycosis can quickly lead to permanent visual loss and potentially fatal cerebral extension. Orbital involvement is almost universally preceded by infection of the paranasal sinuses. Secondary infection of the orbit via direct extension of neighboring cutaneous mucormycosis has not been previously described. The authors present a case of cutaneous mucormycosis with orbital extension in a poorly controlled diabetic patient.

Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states.

Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. "Regionalization"-an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems-may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative's concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states / La regionalización como medio para fortalecer los sistemas de reglamentación: estudio de caso en los estados miembros del CARICOM

Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. “Regionalization”—an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems— may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative’s concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

El mejoramiento de la capacidad básica para la reglamentación farmacológica mediante el fortalecimiento de los sistemas de reglamentación plantea un reto especialmente difícil en contextos de escasos recursos. Una posible solución radica en la “regionalización”, proceso según el cual países con un mismo legado histórico, cultural y lingüístico y con situaciones económicas semejantes colaboran entre sí con objeto de establecer sistemas más eficientes. En el presente informe se describe el Sistema de Reglamentación del Caribe (SRC), iniciativa de regionalización que se está poniendo en marcha en los países de la Comunidad y el Mercado Común del Caribe (CARICOM), pequeños en su mayoría. La iniciativa representa una medida innovadora por fortalecer los sistemas de reglamentación en el Caribe, donde la capacidad existente es más modesta que en otras subregiones de las Américas. En el concepto y diseño de la iniciativa hay elementos y pasos destinados a fomentar la sostenibilidad en contextos de escasos recursos. Estos consisten en aprovechar las plataformas ya existentes para la cooperación, gobernación e infraestructura centralizadas; fortalecer las capacidades de reglamentación que puedan tener la mayor incidencia sobre la salud pública; incorporar políticas que fomenten la confianza en los organismos de reglamentación; modificar el sistema para alentar a la industria a comercializar sus productos en el CARICOM (por ejemplo, utilizando un punto de entrada centralizado para aligerar las cargas reglamentarias); y fortalecer la capacidad en materia de recursos humanos. Si se pone en práctica adecuadamente, el SRC se financiará a sí mismo con las cuotas de los usuarios. La experiencia y las enseñanzas extraídas hasta el momento con la puesta en marcha de esta iniciativa, que se describen en el presente informe, pueden ser útiles como estudio de caso para la formulación de iniciativas afines orientadas a fortalecer la capacidad de reglamentación en entornos de pocos recursos.

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population.

IMPORTANCE: Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE: To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS: This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS: Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES: Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS: We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28,899, for an ICER of $39,475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19,833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81,165 per QALY gained compared with waiting until stage F2; and treating at stage F0, $187,065 per QALY gained compared with waiting until stage F1. Results for other regimens show a similar pattern. At base-case drug prices, treating 50% of all eligible US patients with HCV genotype 1 would cost $53 billion. In sensitivity analyses, the ICER for treating all stages vs treating stages F3 and F4 was most sensitive to cohort age, drug costs, utility values in stages F1 and F2, and percentage of patients eligible for 8-week therapy. Except for patients aged 70 years, the ICER remains less than $100,000 per QALY gained. A 46% reduction in cost of sofosbuvir-ledipasvir therapy decreases the ICER for treating at all fibrosis stages by 48%. CONCLUSIONS AND RELEVANCE: In this simulated model, treating HCV infection at early stages of fibrosis appeared to improve health outcomes and to be cost-effective but incurred substantial aggregate costs. The findings may have implications for health care coverage policies and clinical decision making.

Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study.

OBJECTIVES: To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors DESIGN: Cross sectional study. DATA SOURCES: All applications for which FDA's Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched. RESULTS: 48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact. CONCLUSIONS: FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters.

Computer-aided analysis of orbital volume: a novel technique.

OBJECTIVE: : To demonstrate the accuracy and efficiency of a novel software tool designed specifically for volumetric analysis of the orbit. METHODS: : The software was evaluated for accuracy and speed in analysis of orbital CT data sets. The analysis included: 1) intraoperator error: one operator repeatedly evaluated a single orbit multiple times. The variation in volumes was compared; 2) interoperator error: 3 operators evaluated the same orbits multiple times. The variation in volume measurements among operators was compared; 3) interscan error: one operator evaluated the volume of single orbit scanned on multiple occasions by different CT scanners. The variation in volume measurements among scans performed at different times was compared; and 4) time for analysis: one operator evaluated 52 orbits, recording the time it took to analyze each orbit. RESULTS: : Intraoperator error was 0.08 cc (95% confidence interval, 0.06-0.10). Interoperator error was 0.18 cc (95% confidence interval, 0.14-0.20). Interscan variability data showed a trend toward increasing error for repeated patient scans using different CT scanners. Average time for analysis of single orbit was 138 seconds (standard deviation = 24; range, 95-217 seconds). CONCLUSIONS: : Maxillo is an accurate and efficient tool for semiautomatic evaluation of orbital volume in nontraumatized orbits.