Methodology to standardize heterogeneous statistical data presentations for combining time-to-event oncologic outcomes.

Survival analysis following oncological treatments require specific analysis techniques to account for data considerations, such as failure to observe the time of event, patient withdrawal, loss to follow-up, and differential follow up. These techniques can include Kaplan-Meier and Cox proportional hazard analyses. However, studies do not always report overall survival (OS), disease-free survival (DFS), or cancer recurrence using hazard ratios, making the synthesis of such oncologic outcomes difficult. We propose a hierarchical utilization of methods to extract or estimate the hazard ratio to standardize time-to-event outcomes so that study inclusion into meta-analyses can be maximized. We also provide proof-of concept results from a statistical analysis that compares OS, DFS, and cancer recurrence for robotic surgery to open and non-robotic minimally invasive surgery. In our example, use of the proposed methodology would allow for the increase in data inclusion from 108 hazard ratios reported to 240 hazard ratios reported or estimated, resulting in an increase of 122%. While there are publications summarizing the motivation for these analyses, and comprehensive papers describing strategies to obtain estimates from published time-dependent analyses, we are not aware of a manuscript that describes a prospective framework for an analysis of this scale focusing on the inclusion of a maximum number of publications reporting on long-term oncologic outcomes incorporating various presentations of statistical data.

Cost savings with hemin versus givosiran for the treatment of patients with acute intermittent porphyria (AIP).

OBJECTIVE: Since 1983, hemin has been FDA-approved for acute intermittent porphyria (AIP) attacks. In 2019, FDA approved givosiran for the treatment of adults with acute hepatic porphyria. The objective of this research was to estimate and compare the total cost of AIP-related healthcare for patients treated with hemin or givosiran. METHODS: A microsimulation cost model was developed to estimate the annual economic impact of hemin versus givosiran treatment for patients with AIP from the U.S. healthcare payer perspective. Hemin treatment costs were calculated from the Hemin Shipment Data in which patients were defined as receiving acute attack treatment or prophylaxis treatment based on shipment patterns. Three separate hemin subpopulations were considered: one attack per year, multiple attacks per year, and hemin prophylaxis. Treatment costs for givosiran (with hemin for acute attacks) were simulated based on Phase III trial efficacy results applied to individual treatment histories in the Hemin Shipment Data. Other healthcare utilization was also considered. Outcomes were annualized and expenditures inflated to 2019. RESULTS: For all patients with AIP, the average annual total cost of care with hemin was 78% lower (difference = $482,113; 95% CI=$373,638-$594,778) than the average annual total cost of care with givosiran. Average annual total cost of care with hemin was between 46% and 92% lower than givosiran for the three hemin subpopulations: one attack per year (difference = $545,219; 95% CI=$436,584-$657,239), multiple attacks per year (difference = $459,366; 95% CI=$350,291-$574,403), and hemin prophylaxis (difference = $311,950; 95% CI=$191,898-$435,893). Cost savings with hemin were robust to one-way and probabilistic sensitivity as well as scenario analyses. CONCLUSIONS: Hemin is expected to provide cost savings compared to givosiran for all AIP patients and subpopulations. Lower annual total costs of care with hemin range from $311,950 to $545,219 less depending on whether the patient uses hemin prophylactically or for acute treatment attacks.

Parental Deployment, Adolescent Academic and Social-Behavioral Maladjustment, and Parental Psychological Well-being in Military Families.

OBJECTIVE: Increases in the frequency and length of military deployments have raised concerns about the well-being of military families. We examined the relationship between a military parent's deployment and (1) adolescent academic and social-behavioral maladjustment and (2) parental psychological well-being. METHODS: We collected data from April 2013 through January 2014 from 1021 families of enlisted US Army personnel with children aged 12 or 13 during the Military Teenagers' Environments, Exercise, and Nutrition Study. Through online parent surveys, we collected data on deployment, adolescent academic and social-behavioral maladjustment, and parental psychological well-being. We estimated adjusted logistic and linear regression models for adolescents (all, boys, girls), military parents (all, fathers, mothers), and civilian parents. RESULTS: Compared with no or short deployments, long deployments (>180 days in the past 3 years) were associated with significantly higher odds of decreases in adolescent academic performance (adjusted odds ratio [AOR] = 1.54), independence (AOR = 2.04), and being responsible (AOR = 1.95). These associations were also significant for boys but not for girls. Among parents, long deployments were associated with significantly higher odds of being depressed (AOR = 2.58), even when controlling for adolescent maladjustment (AOR = 2.54). These associations did not differ significantly between military and civilian parents and were significant for military fathers but not military mothers. Recent deployment (in the past 12 months) was not associated with either adolescent or parent outcomes. CONCLUSION: Long deployments are associated with adolescents' academic and social-behavioral maladjustments and diminished parental well-being, especially among boys and military fathers.

gp120-independent HIV infection of cells derived from the female reproductive tract, brain, and colon.

The infection of CD4 cells may have significant involvement in the transmission and long-term persistency of HIV. Using HIV clones carrying the enhanced green fluorescent protein (EGFP), we infected epithelial and glioneuronal cell lines derived from the female reproductive tract, brain, colon, and intestine. HIV infection was quantified by counting EGFP-positive cells. Infection was quantified in cell lines from the female reproductive tract, brain tissue, and colon tissue (0.36%-3.15%). Virus replicated in the infected cells and the progeny virus were infectious for CD4 cells, HeLa-CD4, and CEM T lymphocytes. Furthermore, we found that infection of these epithelial and brain cell lines is independent of gp120. The results from the infection of CD4 epithelial cells suggest that HIV can traverse epithelial cell layers by infecting them through a gp120-independent mechanism. Infection of glial and neuronal cell lines suggests that HIV infection of these cells is a probable mechanism for HIV pathogenicity in the brain and a possible cause for persistent infection in patients.

Involvement of claudin-7 in HIV infection of CD4(-) cells.

BACKGROUND: Human immunodeficiency virus (HIV) infection of CD4(-) cells has been demonstrated, and this may be an important mechanism for HIV transmission. RESULTS: We demonstrated that a membrane protein, claudin-7 (CLDN-7), is involved in HIV infection of CD4(-) cells. A significant increase in HIV susceptibility (2- to 100-fold) was demonstrated when CLDN-7 was transfected into a CD4(-) cell line, 293T. In addition, antibodies against CLDN-7 significantly decreased HIV infection of CD4(-) cells. Furthermore, HIV virions expressing CLDN-7 on their envelopes had a much higher infectivity for 293T CD4(-) cells than the parental HIV with no CLDN-7. RT-PCR results demonstrated that CLDN-7 is expressed in both macrophages and stimulated peripheral blood leukocytes, suggesting that most HIV virions generated in infected individuals have CLDN-7 on their envelopes. We also found that CLDN-7 is highly expressed in urogenital and gastrointestinal tissues. CONCLUSION: Together these results suggest that CLDN-7 may play an important role in HIV infection of CD4(-) cells.