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Aim: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA. Materials & methods: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective. Results: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs. Conclusion: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

Objectives: Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA. Methods: Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model. Results: Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3–5 mg/kg/day) with high-dose L-AmB (10 mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (−1.39 [−2.21, −0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [−1.17, 1.53], 0.50 [−1.11, 2.13] and 0.32 [−0.19, 0.84], respectively) or overall response (−0.99 [−2.21, 0.29], −0.89 [−2.41, 0.65] and 0.06 [−0.43, 0.57], respectively). Conclusions: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.

Aim: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole. Materials & methods: As a matched case–control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs – drug acquisition, monitoring and administration, and hospitalization costs – were estimated from the National Health Service perspective. Results: Per-patient costs for ISAV and liposomal AMB + posaconazole were UK£26,810 and UK£41,855, respectively, with savings primarily driven by drug acquisition and hospitalization costs. Conclusion: ISAV may reduce costs compared with standard mucormycosis therapy.

Research shows that juvenile female offenders have a higher prevalence rate of sexual risk behaviors than girls from the general population and that similar factors underlie both SRBs and delinquent behavior. Contributing to findings derived from young female delinquent samples, this study examines the impact of risk factors on delinquent behaviors and sexual risk behaviors in 146 delinquent girls (12 to 18 years) in outpatient forensic treatment. While controlling for ethnicity, results from structural equation modeling through bootstrapping showed that sexual risk behaviors (explained variance 26%) were predicted by the number of negative life events, peer rejection, and substance use, whereas the number of previous convictions and treatment dropout were predictive of delinquent behavior (explained variance 14.1%). Affiliation with deviant peers, parental monitoring, and conduct problems did not contribute to the explained variance in both outcome measures. These findings will be elaborated on in the discussion.

Background Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden. Methods The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs. Results The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%. Conclusions This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective. Electronic supplementary material The online version of this article (10.1186/s12879-019-3683-2) contains supplementary material, which is available to authorized users.

Bloom’s syndrome (BS) is an autosomal recessive disease, caused by mutations in the BLM gene. This gene codes for BLM protein, which is a helicase involved in DNA repair. DNA repair is especially important for the development and maturation of the T and B cells. Since BLM is involved in DNA repair, we aimed to study if BLM deficiency affects T and B cell development and especially somatic hypermutation (SHM) and class switch recombination (CSR) processes. Clinical data of six BS patients was collected, and immunoglobulin serum levels were measured at different time points. In addition, we performed immune phenotyping of the B and T cells and analyzed the SHM and CSR in detail by analyzing IGHA and IGHG transcripts using next-generation sequencing. The serum immunoglobulin levels were relatively low, and patients had an increased number of infections. The absolute number of T, B, and NK cells were low but still in the normal range. Remarkably, all BS patients studied had a high percentage (20–80%) of CD4+ and CD8+ effector memory T cells. The process of SHM seems normal; however, the Ig subclass distribution was not normal, since the BS patients had more IGHG1 and IGHG3 transcripts. In conclusion, BS patients have low number of lymphocytes, but the immunodeficiency seems relatively mild since they have no severe or opportunistic infections. Most changes in the B cell development were seen in the CSR process; however, further studies are necessary to elucidate the exact role of BLM in CSR. Electronic supplementary material The online version of this article (10.1007/s10875-017-0454-y) contains supplementary material, which is available to authorized users.