Cost-Effectiveness of Strategies for Treatment Timing for Perinatally Acquired Hepatitis C Virus.

Importance: Prevalence of chronic hepatitis C virus (HCV) infection among pregnant people is increasing in the US. HCV is transmitted vertically in 7% to 8% of births. Direct-acting antiviral (DAA) therapy was recently approved for children with HCV who are 3 years or older. The clinical and economic impacts of early DAA therapy for young children with HCV, compared with treating at older ages, are unknown. Objective: To develop a state-transition model to project clinical and economic outcomes for children with perinatally acquired HCV to investigate the cost-effectiveness of treating at various ages. Design, Setting, and Participants: The study team modeled the natural history of perinatally acquired HCV to simulate disease progression and costs of a simulated a cohort of 1000 US children with HCV from 3 years old through death. Added data were analyzed January 5, 2021, through July 1, 2022. Interventions: The study compared strategies offering 8 weeks of DAA therapy at 3, 6, 12, or 18 years old, as well as a comparator of never treating HCV. Main Outcomes and Measures: Outcomes of interest include life expectancy from 3 years and average lifetime per-person health care costs. Other clinical outcomes include cases of cirrhosis, decompensated cirrhosis, and hepatocellular carcinoma (HCC). Results: The study team projected that treating HCV at 3 years old was associated with lower mean lifetime per-person health care costs ($148 162) than deferring treatment until 6 years old ($164 292), 12 years old ($171 909), or 18 years old ($195 374). Projected life expectancy was longest when treating at 3 years old (78.36 life years [LYs]) and decreased with treatment deferral until 6 years old (76.10 LYs), 12 years old (75.99 LYs), and 18 years old (75.46 LYs). In a cohort of 1000 children with perinatally acquired HCV, treating at 3 years old prevented 89 projected cases of cirrhosis, 27 cases of HCC, and 74 liver-related deaths compared with deferring treatment until 6 years old. In sensitivity analyses, increasing loss to follow-up led to even greater clinical benefits and cost savings with earlier treatment. Conclusions and Relevance: These study results showed that DAA therapy for 3-year-old children was projected to reduce health care costs and increase survival compared with deferral until age 6 years or older. Measures to increase DAA access for young children will be important to realizing these benefits.

Test characteristics for combining non-invasive liver fibrosis staging modalities in individuals with Hepatitis C virus.

Non-invasive methods have largely replaced biopsy to identify advanced fibrosis in hepatitis C virus (HCV). Guidelines vary regarding testing strategy to balance accuracy, costs and loss to follow-up. Although individual test characteristics are well-described, data comparing the accuracy of using two tests together are limited. We calculated combined test characteristics to determine the utility of combined strategies. This study synthesizes empirical data from fibrosis staging trials and the literature to estimate test characteristics for Fibrosis-4 (FIB4), APRI or a commercial serum panel (FibroSure®), followed by transient elastography (TE) or FibroSure®. We simulated two testing strategies: (1) second test only for those with intermediate first test results (staged approach), and (2) second test for all. We summarized empiric data with multinomial distributions and used this to estimate test characteristics of each strategy on a simulated population of 10,000 individuals with 4.2% cirrhosis prevalence. Negative predictive value (NPV) for cirrhosis from a single test ranged from 98.2% (95% CB 97.6-98.8%) for FIB-4 to 99.4% (95% CB 99.0-99.8%) for TE. Using a staged approach with TE second, sensitivity for cirrhosis rose to 93.3-96.9%, NPV to 99.7-99.8%, while PPV dropped to <32%. Using TE as a second test for all minimally changed estimated test characteristics compared with the staged approach. Combining two non-invasive fibrosis tests barely improves NPV and decreases or does not change PPV compared with a single test, challenging the utility of serial testing modalities. These calculated combined test characteristics can inform best methods to identify advanced fibrosis in various populations.

A Microsimulation Study of the Cost-Effectiveness of Hepatitis C Virus Screening Frequencies in Hemodialysis Centers.

BACKGROUND: National guidelines recommend twice-yearly hepatitis C virus (HCV) screening for patients receiving in-center hemodialysis. However, studies examining the cost-effectiveness of HCV screening methods or frequencies are lacking. METHODS: We populated an HCV screening, treatment, and disease microsimulation model with a cohort representative of the US in-center hemodialysis population. Clinical outcomes, costs, and cost-effectiveness of the Kidney Disease Improving Global Outcomes (KDIGO) 2018 guidelines-endorsed HCV screening frequency (every 6 months) were compared with less frequent periodic screening (yearly, every 2 years), screening only at hemodialysis initiation, and no screening. We estimated expected quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) between each screening strategy and the next less expensive alternative strategy, from a health care sector perspective, in 2019 US dollars. For each strategy, we modeled an HCV outbreak occurring in 1% of centers. In sensitivity analyses, we varied mortality, linkage to HCV cure, screening method (ribonucleic acid versus antibody testing), test sensitivity, HCV infection rates, and outbreak frequencies. RESULTS: Screening only at hemodialysis initiation yielded HCV cure rates of 79%, with an ICER of $82,739 per QALY saved compared with no testing. Compared with screening at hemodialysis entry only, screening every 2 years increased cure rates to 88% and decreased liver-related deaths by 52%, with an ICER of $140,193. Screening every 6 months had an ICER of $934,757; in sensitivity analyses using a willingness-to-pay threshold of $150,000 per QALY gained, screening every 6 months was never cost-effective. CONCLUSIONS: The KDIGO-recommended HCV screening interval (every 6 months) does not seem to be a cost-effective use of health care resources, suggesting that re-evaluation of less-frequent screening strategies should be considered.

Fungal Infectious Interface Keratitis Presenting 2 Years After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to describe infectious interface keratitis after Descemet membrane endothelial keratoplasty (DMEK) more than 2 years after surgery. METHODS: A case study. RESULTS: In this study, we report a case of fungal infectious interface keratitis occurring 2 years after uncomplicated Descemet membrane endothelial keratoplasty. The donor corneal rim culture at the time of surgery grew a single colony of Candida albicans/dubliniensis , but the patient was not treated with antifungals at that time. At the onset of clinical infection, more than 2 years postoperatively, the patient was treated with systemic antifungals and adjuvant intrastromal amphotericin-B injection. The patient subsequently required penetrating keratoplasty with ultimately well-preserved visual acuity. CONCLUSIONS: Fungal infectious interface keratitis (IIK) is a rare complication associated with lamellar keratoplasty. Although most common in the early postoperative period, this complication can occur several years after successful transplantation. Management may require a combination of systemic and stromal antifungal therapy. However, some patients may eventually require penetrating keratoplasty for definitive treatment.

"Meds-in-Hand" Intervention to Reduce Critical Process Delays in Pediatric Human Immunodeficiency Virus Post-Exposure Prophylaxis.

Pediatric human immunodeficiency virus post-exposure prophylaxis is frequently indicated, but delays in medication receipt are common. Using plan-do-study-act cycles, we developed a multidisciplinary collaboration to reduce critical process delays in our pediatric emergency department. Interruptions decreased from a median 1 per month pre-intervention to zero per month during the intervention.

Short-Term Effects and Long-Term Cost-Effectiveness of Universal Hepatitis C Testing in Prenatal Care.

OBJECTIVE: To estimate the clinical effects and cost-effectiveness of universal prenatal hepatitis C screening, and to calculate potential life expectancy, quality of life, and health care costs associated with universal prenatal hepatitis C screening and linkage to treatment. METHODS: Using a stochastic individual-level microsimulation model, we simulated the lifetimes of 250 million pregnant women matched at baseline with the U.S. childbearing population on age, injection drug use behaviors, and hepatitis C virus (HCV) infection status. Modeled outcomes included hepatitis C diagnosis, treatment and cure, lifetime health care costs, quality-adjusted life years (QALY) and incremental cost-effectiveness ratios comparing universal prenatal hepatitis C screening to current practice. We modeled whether neonates exposed to maternal HCV at birth were identified as such. RESULTS: Pregnant women with hepatitis C infection lived 1.21 years longer and had 16% lower HCV-attributable mortality with universal prenatal hepatitis C screening, which had an incremental cost-effectiveness ratio of $41,000 per QALY gained compared with current practice. Incremental cost-effectiveness ratios remained below $100,000 per QALY gained in most sensitivity analyses; notable exceptions included incremental cost-effectiveness ratios above $100,000 when assuming mean time to cirrhosis of 70 years, a cost greater than $500,000 per false positive diagnosis, or population HCV infection prevalence below 0.16%. Universal prenatal hepatitis C screening increased identification of neonates exposed to HCV at birth from 44% to 92%. CONCLUSIONS: In our model, universal prenatal hepatitis C screening improves health outcomes in women with HCV infection, improves identification of HCV exposure in neonates born at risk, and is cost-effective.

Transepithelial crosslinking retreatment of progressive corneal ectasia unresponsive to classic crosslinking.

A 41-year-old man presented 10 years after uneventful laser in situ keratomileusis (LASIK) with symptomatic post-LASIK ectasia. He had treatment with the classic Dresden epithelium-off technique and presented 4 years later with progression of the ectasia. He was subsequently retreated with conductive keratoplasty (CK) followed by a new proprietary epithelium-on corneal collagen crosslinking (CXL) procedure using a proprietary transepithelial riboflavin formulation and delivery system on the following day. One year after retreatment, the patient noted stable vision in the treated eye with a corrected distance visual acuity (CDVA) of 20/60+. Thus, epithelium-on CXL, if performed with appropriate formulations and delivery technology as well as careful attention to appropriate riboflavin loading of the stroma, can stabilize an ectatic cornea. In addition, when performed prior to CXL, CK can induce a significant, lasting improvement in corneal shape and CDVA. This technique merits further study.

Histopathologic analysis of successful endothelial keratoplasty following multiple failed keratoplasties.

UNLABELLED: A 68-year-old woman with bilateral keratoconus presented with persistent visual acuity deficits following cataract extraction with a neodymium:YAG capsulotomy in the right eye 2 years earlier. Penetrating keratoplasty (PKP) had been performed for keratoconus in the right eye without complications until steroid drops were discontinued after 10 years because of persistent elevated intraocular pressure. The right eye experienced immunologic rejection and failure of 3 PKPs, 1 Descemet-stripping endothelial keratoplasty (DSEK), and a trabeculectomy with an eventual anatomically successful DSEK before the patient died at 95 years of age. The left eye improved following a single PKP. Postmortem histopathologic analysis of the cornea showed an anatomically successful DSEK graft with intact donor Descemet membrane and viable graft endothelial cells. To our knowledge, this is the first histopathologic analysis of an anatomically successful DSEK after multiple failed PKPs and trabeculectomy. The course in this case supports early consideration of lamellar keratoplasty, especially in patients with ocular comorbidities. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Capsulorhexis phimosis with anterior flexing of an accommodating IOL: case report and histopathological analyses.

We describe the case of a patient who had cataract surgery with implantation of an accommodating hydrophilic acrylic intraocular lens (IOL) that exhibited capsulorhexis phimosis and in-the-bag IOL luxation leading to explantation of the IOL-capsular bag complex 10 years after implantation. Constriction of the capsular bag secondary to fibrosis caused significant anterior flexing of the haptic elements of the IOL. Histopathological analysis revealed dense anterior subcapsular fibrosis and fibrous metaplasia of the anterior lens epithelial cells. No signs suggestive of pseudoexfoliation were found. This case raises concerns related to the continuously evolving indications for implantation of accommodating and other highly flexible IOLs (eg, microincision IOLs), particularly in patients with no clear predisposition to zonular weakness and, accordingly, excessive capsular bag contraction.

Screening for sleep disordered breathing among applicants for a professional driver's license.

OBJECTIVES: Individuals with sleep disordered breathing (SDB) are at high risk for falling asleep while driving. The aim of this study was to identify variables that would predict SDB among healthy young applicants for a professional driver's license. METHOD: A total of 301 applicants for a driver's license completed self-administered questionnaires. Sleep was recorded for one night with the Watch peripheral arterial tone-100. To identify possible predictors of SDB (Respiratory Disturbance Index >15), we employed new statistical methods. RESULTS: The following items were identified as significant predictors of SDB: body mass index, age, Mini Sleep Questionnaire, smoking, father snoring, afternoon nap-taking, and falling asleep while traveling as a passenger. Moderate or severe SDB was prevalent in at least 25% of the applicants. CONCLUSION: New statistical methods revealed that a combination of questions related to sleep habits, complaints, and demographic data predicted most of the clinically significant SDB.

A rare case of idiopathic neutrophilic dermatosis of the hands.

Neutrophilic dermatosis of the hands is a rare localized variant of Sweet syndrome. The following is a case report of a 68-year-old man who presented to our clinic with progressive redness, swelling, and decreased mobility of the fingers. Examination revealed symmetric, violaceous, edematous, annular plaques and nodules on the dorsal and lateral surfaces of the thumb and index fingers. Biopsy demonstrated a dense neutrophilic infiltrate in the papillary dermis without evidence of vasculitis, changes consistent with Sweet syndrome. A thorough work up revealed no concurrently associated condition. Treatment with prednisone 10 mg daily, colchicine 0.6 mg twice daily, and pentoxifylline 400 mg three times daily resulted in significant improvement in this case of idiopathic neutrophilic dermatosis of the hands.

Effect of mitomycin C on the corneal endothelium when used for corneal subepithelial haze prophylaxis following photorefractive keratectomy.

PURPOSE: To evaluate the potential effect of topical mitomycin C (MMC) on the corneal endothelium of myopic patients undergoing photorefractive keratectomy (PRK). METHODS: Sixteen eyes with a planned ablation depth >75 microm underwent PRK followed by 0.02% MMC applied for 12 seconds using a methylcellulose sponge. Endothelial specular microscopy was performed with the Keeler-Konan specular photomicroscope in 16 eyes before and at least 1 year after surgery. Mean follow-up was 18 months (range: 12 to 24 months). Mean cell density, coefficient of variation of mean cell area, and percentage of hexagonal cells were measured and calculated using computerized morphometric analysis. RESULTS: Mean endothelial cell densities before and after surgery were 2882 +/- 783 cells/mm2 (range: 1511 to 4022 cells/mm2) and 2867 +/- 588 cells/mm2 (range: 1638 to 3881 cells/mm2), respectively (P > .05). Mean coefficient of variation before and after surgery was 0.30 +/- 0.07 (range: 0.23 to 0.49) and 0.26 +/- 0.04 (range: 0.22 to 0.33), respectively (P=.06). Mean percentage of hexagonal cells before and after surgery was 61% +/- 6.8% (range: 47% to 70%) and 66% +/- 6.7% (range: 54% to 75%), respectively. CONCLUSIONS: Administration of MMC for haze prophylaxis following PRK did not have a significant effect on quantitative endothelial cell density or qualitative morphometric parameters in this study.