The societal cost of treatment-seeking patients with borderline personality disorder in Germany

According to previous research, borderline personality disorder (BPD) is associated with high cost-of-illness. However, there is still a shortage of cost-of-illness-studies assessing costs from a broad societal perspective, including direct and indirect costs. Further, there are considerable differences in the results among the existing studies. In the present study, 167 German men and women seeking specialized outpatient treatment for BPD were included. We assessed societal cost-of-illness bottom-up through structured face-to-face interviews and encompassed a wide range of cost components. All costs were calculated for the 2015 price level. Cost-of-illness amounted to € 31,130 per patient and year preceding disorder-specific outpatient treatment. € 17,044 (54.8%) were direct costs that were mostly related to hospital treatment. Indirect costs amounted to € 14,086 (45.2%). Within indirect costs, costs related to work disability were the most crucial cost driver. The present study underlines the tremendous economic burden of BPD. According to the present study, both the direct and indirect costs are of significant importance for the societal costs associated with BPD. Besides the need for more disorder-specific treatment facilities for men and women with BPD, we assume that education and employment are topics that should be specifically targeted and individually supported at an early stage of treatment.Trial Registration: German Clinical Trial Registration, DRKS00011534, Date of Registration: 11/01/2017, retrospectively registered.

Discovery of a Novel Class of Norovirus Inhibitors with High Barrier of Resistance

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting in ~219,000 deaths annually and a societal cost of ~USD60 billion. There are no antivirals or vaccines available to treat and/or prevent HuNoV. In this study, we performed a large-scale phenotypical antiviral screening using the mouse norovirus (MNV), which included ~1000 drug-like small molecules from the Drug Design and Synthesis Centre (Sapienza University, Rome). Compound 3-((3,5-dimethylphenyl)sulfonyl)-5-chloroindole-N-(phenylmethanol-4-yl)-2.carboxamide (compound 1) was identified as an inhibitor of MNV replication with an EC50 of 0.5 ± 0.1 µM. A series of 10 analogs were synthesized of which compound 6 showed an improved potency/selectivity (EC50 0.2 ± 0.1 µM) against MNV; good activity was also observed against the HuNoV GI replicon (EC50 1.2 ± 0.6 µM). Time-of-drug-addition studies revealed that analog 6 acts at a time point that coincides with the onset of viral RNA replication. After six months of selective pressure, two compound 6res variants were independently selected, both harboring one mutation in VPg and three mutations in the RdRp. After reverse engineering S131T and Y154F as single mutations into the MNV backbone, we did not find a markedly compound 6res phenotype. In this study, we present a class of novel norovirus inhibitors with a high barrier to resistance and in vitro antiviral activity.

A Novel Class of Norovirus Inhibitors Targeting the Viral Protease with Potent Antiviral Activity In Vitro and In Vivo

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to the protease inhibitor rupintrivir. The early hit compound 4 inhibited the replication of murine norovirus (MNV) and the HuNoV GI.1 replicon in vitro (EC50 ~1 µM) and swiftly cleared the HuNoV GI.1 replicon from the cells. Compound 4 still inhibits the proteolytic activity. We selected a resistant GI.1 replicon, with a mutation (I109V) in a highly conserved region of the viral protease, conferring a low yield of resistance against compound 4 and rupintrivir. After testing new derivatives, compound 10d was the most potent (EC50 nanomolar range). Molecular docking indicated that the aldehyde group of compounds 4 and 10d bind with Cys139 in the HuNoV 3CL protease by a covalent linkage. Finally, compound 10d inhibited the replication of HuNoV GII.4 in infected zebrafish larvae, and PK studies in mice showed an adequate profile.

The societal cost and economic impact of surgical care on patients’ households in rural Uganda; a mixed method study

Background The epidemiology and cost of surgical care delivery in low-and middle-income countries (LMICs) is poorly understood. This study characterizes the cost of surgical care, rate of catastrophic medical expenditure and medical impoverishment, and impact of surgical hospitalization on patients’ households at Soroti Regional Referral Hospital (SRRH), Uganda. Methods We prospectively collected demographic, clinical, and cost data from all surgical inpatients and caregivers at SRRH between February 2018 and January 2019. We conducted and thematically analyzed qualitative interviews to discern the impact of hospitalization on patients’ households. We employed the chi-square, t-test, ANOVA, and Bonferroni tests and built regression models to identify predictors of societal cost of surgical care. Out of pocket spending (OOPS) and catastrophic expenses were determined. Results We encountered 546 patients, mostly male (62%) peasant farmers (42%), at a median age of 22 years; and 615 caregivers, typically married (87%), female (69%), at a median age of 35 years. Femur fractures (20.4%), soft tissue infections (12.3%), and non-femur fractures (11.9%) were commonest. The total societal cost of surgical care was USD 147,378 with femur fractures (USD 47,879), intestinal obstruction (USD 18,737) and non-femur fractures (USD 10,212) as the leading contributors. Procedures (40%) and supplies (12%) were the largest components of societal cost. About 29% of patients suffered catastrophic expenses and 31% were medically impoverished. Conclusion Despite free care, surgical conditions cause catastrophic expenses and impoverishment in Uganda. Femur fracture is the most expensive surgical condition due to prolonged hospitalization associated with traction immobilization and lack of treatment modalities with shorter hospitalization.

Productivity burden borne by the parents of persons with Angelman syndrome

Purpose Angelman syndrome (AS) is a severe neurodevelopmental condition associated with a significant socioeconomic burden. However, no studies have thus far quantified or monetised the parental productivity burden of AS. The present study sought to estimate this burden. Methods The parental productivity burden of AS in Australia was estimated using cost-of-illness modelling with simulated follow-up over a 10-year period using 2019 as the baseline year. This involved estimating the prevalence of persons with AS and their parents, the productivity adjusted life years (PALYs) lost by parents, and the corresponding cost to society. Results The productivity burden borne by the estimated 153 to 1,322 (lower to upper scenario) parents of the 199 to 1,714 persons with AS ranged from 229.6 to 1,980.2 PALYs (discounted). This corresponded to a societal cost (discounted) of AUD$21.0 to $181.2 million, and a loss of 38% of PALYs per-parent. Conclusion AS imposes a significant productivity burden on Australian parents of affected persons, with a large associated impact on the broader economy. These findings are important for informing government planning regarding the supports that should be provided to persons with AS and their families. They will also be important for informing the reimbursement strategy for AS therapies.

Lockdown as a last resort option in case of COVID-19 epidemic rebound: a modelling study

Background Given its high economic and societal cost, policymakers might be reluctant to implement a large-scale lockdown in case of coronavirus disease (COVID-19) epidemic rebound. They may consider it as a last resort option if alternative control measures fail to reduce transmission. Aim We developed a modelling framework to ascertain the use of lockdown to ensure intensive care unit (ICU) capacity does not exceed a peak target defined by policymakers. Methods We used a deterministic compartmental model describing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the trajectories of COVID-19 patients in healthcare settings, accounting for age-specific mixing patterns and an increasing probability of severe outcomes with age. The framework is illustrated in the context of metropolitan France. Results The daily incidence of ICU admissions and the number of occupied ICU beds are the most robust indicators to decide when a lockdown should be triggered. When the doubling time of hospitalisations estimated before lockdown is between 8 and 20 days, lockdown should be enforced when ICU admissions reach 3.0–3.7 and 7.8–9.5 per million for peak targets of 62 and 154 ICU beds per million (4,000 and 10,000 beds for metropolitan France), respectively. When implemented earlier, the lockdown duration required to get back below a desired level is also shorter. Conclusions We provide simple indicators and triggers to decide if and when a last-resort lockdown should be implemented to avoid saturation of ICU. These metrics can support the planning and real-time management of successive COVID-19 pandemic waves.