Cost-effectiveness analysis of hepatocellular carcinoma screening by combinations of ultrasound and alpha-fetoprotein among Alaska Native people, 1983–2012

Background: The American Association for the Study of Liver Diseases (AASLD) recommends semi-annual hepatocellular carcinoma (HCC) screening using ultrasound (US) in persons with chronic hepatitis B (CHB) virus infection at high risk for HCC such as Asian males aged ≥40 years and Asian females aged ≥50 years. Objective: To analyse the cost-effectiveness of 2 HCC screening methods in the Alaska Native (AN) health system: US-alone, or screening by alpha-fetoprotein (AFP) initially and switching to US for subsequent screenings if AFP >10 ng/mL (AFP→US). Design: A spreadsheet-based model was developed for accounting the costs of 2 hypothetical HCC screening methods. We used epidemiologic data from a cohort of 839 AN persons with CHB who were offered HCC screening by AFP/US semi-annually during 1983–2012. We assumed that compared with AFP→US, US-alone identifies 33% more tumours at an early stage (defined as a single tumour ≤5 cm or ≤3 tumours ≤3 cm in diameter). Years of life gained (YLG) attributed to screening was estimated by comparing additional years of survival among persons with early- compared with late-stage tumours. Screening costs were calculated using Medicare reimbursement rates in 2012. Future screening costs and YLG were projected over a 30-year time horizon using a 3% discount rate. Results: The total cost of screening for the cohort by AFP→US would have been approximately $357,000 ($36,000/early-stage tumour detected) compared to $814,000 ($59,000/early-stage tumour detected) by US-alone. The AFP→US method would have yielded an additional 27.8 YLG ($13,000/YLG) compared with 38.9 YLG ($21,000/YLG) for US-alone. Screening by US-alone would incur an additional $114,000 per extra early-tumour detected compared with AFP→US and$41,000 per extra YLG. Conclusions: Although US-alone HCC screening might have yielded more YLG than AFP→US, the reduced costs of the AFP→US method could expand access to HCC screening in resource constrained settings

Potentially preventable hospitalizations for acute and chronic conditions in Alaska, 2010–2012

Objective: The U.S. Agency for Healthcare Research and Quality's Prevention Quality Indicators comprise acute and chronic conditions for which hospitalization can be potentially prevented by high-quality ambulatory care. The Healthy Alaska 2020 initiative (HA2020) targeted reducing potentially preventable hospitalizations (PPH) for acute and chronic conditions among its health indicators. We estimated the PPH rate for adults aged ≥18 years in Alaska during 2010–2012. Methods: We conducted a cross-sectional analysis of state-wide hospital discharge data obtained from the Healthcare Cost and Utilization Project and the Indian Health Service. We calculated average annual PPH rates/1000 persons for acute/chronic conditions. Age-adjusted rate ratios (aRRs) were used for evaluating PPH rate disparities between Alaska Native (AN) and non-AN adults. Results: Among 127,371 total hospitalizations, 4911 and 6721 were for acute and chronic PPH conditions, respectively. The overall crude PPH rate was 7.3 (3.1 for acute and 4.2 for chronic conditions). AN adults had a higher rate than non-AN adults for acute (aRR: 4.7; p < 0.001) and chronic (aRR: 2.6; p < 0.001) PPH conditions. Adults aged ≥85 years had the highest PPH rate for acute (43.5) and chronic (31.6) conditions. Acute conditions with the highest PPH rate were bacterial pneumonia (1.8) and urinary tract infections (0.8). Chronic conditions with the highest PPH rate were chronic obstructive pulmonary disease (COPD; 1.6) and congestive heart failure (CHF; 1.3). Conclusion: Efforts to reduce PPHs caused by COPD, CHF, and bacterial pneumonia, especially among AN people and older adults, should yield the greatest benefit in achieving the HA2020 goal. Keywords: Quality of health care, Health services research, Native American, Healthcare disparitie

Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8.

Congenital hypothyroidism (CH) is a relatively frequent and potentially severe disease. It is classically subdivided into: 1) thyroid dysgenesis (TD), a defect in the organogenesis of the gland leading to hypoplastic, ectopic, or absent thyroid gland; or 2) thyroid dyshormonogenesis, a defect in one of the biochemical mechanisms responsible for thyroid hormone synthesis. Most cases of TD are sporadic, although familial occurrences have occasionally been described. Recently, several genes have been implicated in a small proportion of TD, but, in the majority of the cases, the etiology remains unknown. PAX8 is a transcription factor involved in thyroid development. So far, three loss-of-function mutations of PAX8 have been described, two in sporadic cases and one in familial thyroid hypoplasia. Here, we describe a novel mutation of PAX8 causing autosomal dominant transmission of CH with thyroid hypoplasia. The mutation consists of the substitution of a tyrosine for cysteine 57 in the paired domain of PAX8. When tested in cotransfection experiments with a thyroid peroxidasse promoter construct, the mutant allele was unable to exert its normal transactivation effect on transcription. Our results give further evidence that, contrary to the situation in knockout mice, haplo-insufficiency of PAX8 is a cause of CH in humans.Case ReportsJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States.

Data on the detailed clinical progression of COVID-19 in conjunction with epidemiological and virological characteristics are limited. In this case series, we describe the first 12 US patients confirmed to have COVID-19 from 20 January to 5 February 2020, including 4 patients described previously1,2,3. Respiratory, stool, serum and urine specimens were submitted for SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) testing, viral culture and whole genome sequencing. Median age was 53 years (range: 21–68); 8 patients were male. Common symptoms at illness onset were cough (n = 8) and fever (n = 7). Patients had mild to moderately severe illness; seven were hospitalized and demonstrated clinical or laboratory signs of worsening during the second week of illness. No patients required mechanical ventilation and all recovered. All had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2–3 weeks after illness onset. Lowest real-time PCR with reverse transcription cycle threshold values in the upper respiratory tract were often detected in the first week and SARS-CoV-2 was cultured from early respiratory specimens. These data provide insight into the natural history of SARS-CoV-2. Although infectiousness is unclear, highest viral RNA levels were identified in the first week of illness. Clinicians should anticipate that some patients may worsen in the second week of illness