Felipe Perez, MD

View details for Web of Science ID 000619264500327

Abstract

Teleost fish continues to grow their eyes throughout life with the body size. In Astatotilapia burtoni, the fish retina increases by adding new retinal cells at the ciliary marginal zone (CMZ) and in the outer nuclear layer (ONL). Cell proliferation at both sites exhibits a daily rhythm in number of dividing cells. To understand how this diurnal rhythm of new cell production is controlled in retinal progenitor cells, we studied the transcription pattern of clock genes in retina, including clock1a, clock1b, bmal1a (brain and muscle ARNT-Like), and per1b (period1b). We found that these genes have a strong diurnal rhythmic transcription during light-dark cycles but not in constant darkness. An oscillation in pcna transcription was also observed during light-dark cycles, but again not in constant darkness. Our results also indicate an association between Clock proteins and the upstream region of pcna (proliferating cellular nuclear antigen) gene. A luciferase reporter assay conducted in an inducible clock knockdown cell line further demonstrated that the mutation on predicted E-Boxes in pcna promoter region significantly attenuated the transcriptional activation induced by Clock protein. These results suggested that the diurnal rhythmic expression of clock genes in A.burtoni retina could be light dependent and might contribute to the daily regulation of the proliferation of the retina progenitors through key components of cell cycle machinery, for instance, pcna.

View details for DOI 10.1016/j.exer.2017.04.004

View details for PubMedID 28434813

Abstract

BACKGROUND: Clinic no shows (NS) create a lost opportunity for provider-patient interaction and impose a financial burden to the healthcare system and on society. We aimed to: (1) to determine the clinical and demographic factors associated with increased NS rates at a children's hospital's subsubspecialty clinics and (2) to estimate the direct institutional financial costs associated with NS events. METHODS: A comprehensive database was generated from all clinic encounters for 15 subspecialty outpatient clinics (five surgical and 10 medical) between September 12, 2005 and December 30, 2010. Multivariate logistic regressions were performed to identify the variables associated with NS events. Direct costs of NS events were estimated using annual revenue for each clinic. RESULTS: A total of 284,275 encounters and 17,024 NS events were available for analysis. Public insurance coverage (Medicaid and Title V), compared to private insurance or self-pay status, was associated with an increased likelihood NS (OR 2.19, 95% CI 2.10-2.28, p < 0.0005 for Medicaid; OR 1.56, 95% CI 1.50-1.62, p < 0.0005 for Title V). Compared to patients 21-30 years of age, patients <12 years (OR 2.08, 95% CI 1.77-2.45, p < 0.0005) had increased likelihood of NS. Scheduled visits with medical subspecialists were more likely than surgical subspecialty visits to result in a NS (OR 1.69, 95% CI 1.63-1.75, p < 0.0005). The predicted annualized lost revenue associated with NS visits was estimated at $730,000 from the 15 clinics analyzed, approximately $210 per NS event. CONCLUSION: Pediatric subspecialty NS events are common, costly, and potentially preventable.

View details for Web of Science ID 000348450800003

View details for PubMedID 23551280

Abstract

Inflammatory bowel diseases are costly chronic gastrointestinal diseases. We aimed to determine whether immediate colectomy with ileal pouch-anal anastamosis (IPAA) after diagnosis of severe ulcerative colitis (UC) was cost-effective compared to the standard medical therapy.We created a Markov model simulating 2 cohorts of 21-year-old patients with severe UC, following them until 100 years of age or death, comparing early colectomy with IPAA strategy to the standard medical therapy strategy. Deterministic and probabilistic analyses were performed.Standard medical care accrued a discounted lifetime cost of $236,370 per patient. In contrast, early colectomy with IPAA accrued a discounted lifetime cost of $147,763 per patient. Lifetime quality-adjusted life-years gained (QALY-gained) for standard medical therapy was 20.78, while QALY-gained for early colectomy with IPAA was 20.72. The resulting incremental cost-effectiveness ratio (costs/QALY) was approximately $1.5 million per QALY-gained. Results were robust to one-way sensitivity analyses for all variables in the model. Quality-of-life after colectomy with IPAA was the most sensitive variable impacting cost-effectiveness. A low utility value of less than 0.7 after colectomy with IPAA was necessary for the colectomy with IPAA strategy to be cost-ineffective.Under the appropriate clinical settings, early colectomy with IPAA after diagnosis of severe UC reduces health care expenditures and provides comparable quality of life compared to exhaustive standard medical therapy.

View details for DOI 10.1097/SLA.0b013e3182445321

View details for Web of Science ID 000306083300020

View details for PubMedID 22270693

Abstract

Inflammatory bowel diseases (IBDs) are costly chronic gastrointestinal diseases, with pediatric IBD representing increased costs per patient compared to adult disease. Health care expenditures for ulcerative colitis (UC) are >$2 billion annually. It is not clear whether the addition of VSL#3 to standard medical therapy in UC induction and maintenance of remission is a cost-effective strategy.We performed a systematic review of the literature and created a Markov model simulating a cohort of 10-year-old patients with severe UC, studying them until 100 years of age or death. We compared 2 strategies: standard medical therapy versus medical therapy + VSL#3. For both strategies, we assumed that patients progressed through escalating therapies--mesalamine, azathioprine, and infliximab--before receiving a colectomy + ileal pouch anal anastamosis (IPAA) if the 3 medical therapy options were exhausted. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), defined as the difference of costs between strategies for each quality-adjusted life-year (QALY) gained. One-way sensitivity analyses were performed on variables to determine the key variables affecting cost-effectiveness.Standard medical care accrued a lifetime cost of $203,317 per patient, compared to $212,582 per patient for medical therapy + VSL#3. Lifetime QALYs gained was comparable for standard medical therapy and medical therapy + VSL#3 at 24.93 versus 25.05, respectively. Using the definition of ICER <50,000/QALY as a cost-effective intervention, medical therapy + VSL#3 produced an ICER of $79,910 per QALY gained, making this strategy cost-ineffective. Sensitivity analyses showed that 4 key parameters could affect the cost-effectiveness of the 2 strategies: cost of colectomy + IPAA, maintenance cost after surgery, probability of developing pouchitis after surgery, and the quality of life after a colectomy + IPAA. High surgical and postsurgical costs, a high probability of developing pouchitis, and a low quality of life after a colectomy + IPAA could make adjunct VSL#3 use a cost-effective strategy.Given present data, adjunct VSL#3 use for pediatric UC induction and maintenance of remission is not cost-effective, although several key parameters could make this strategy cost-effective. The quality of life after an IPAA is the single most important variable predicting whether this procedure benefits patients over escalating standard medical therapy.

View details for DOI 10.1097/MPG.0b013e3182293a5e

View details for Web of Science ID 000296383000007

View details for PubMedID 21694634

View details for Web of Science ID 000208812703337