Variation in processes of care for total hip arthroplasty across high-income countries.

Total hip arthroplasty (THA) is among the most commonly performed elective surgeries in high-income countries, and wait times for THA have frequently been cited by US commentators as evidence that countries with universal insurance programs or national health systems "ration" care. This novel qualitative study explores processes of care for hip replacement in the United States and 6 high-income countries with a focus on eligibility, wait times, decision-making, postoperative care, and payment policies. We found no evidence of rationing or government interference in decision-making across high-income countries. Compared with the 6 other high-income countries in our study, the United States has developed efficient care processes that often allow for a same-day discharge. In contrast, THA patients in Germany stay in the hospital 7-9 days and receive 2-3 weeks of inpatient rehabilitation. However, the payment per THA in the United States remains far above other countries, despite far fewer inpatient days.

SARS-CoV-2 Antibody and T Cell Response after a Third Vaccine Dose in Hemodialysis Patients Compared with Healthy Controls.

Hemodialysis (HD) patients have an increased risk of severe SARS-CoV-2 infection. In this study, we assess the impact of a third vaccine dose (3D) on antibody levels and T cell response in HD patients and a healthy control group in a prospective cohort study consisting of 60 HD patients and 65 healthy controls. Each participant received two doses of the BNT-162b2 mRNA vaccine and an mRNA vaccine 3D. The SARS-CoV-2 antibody response was measured 6 months after the second vaccine dose and 6 to 8 weeks after the 3D. We assessed INF-γ secretion 6-8 weeks post 3D in 24 healthy controls, 17 HD patients with a normal response, and 20 low responder HD patients. The groups were compared using univariate quantile regressions and multiple analyses. After the 3D, the SARS-CoV-2-specific antibody and INF-γ titers of most HD patients were comparable to those of healthy controls. A subgroup of HD patients who had shown a diminished antibody response after the first two vaccine doses developed a significantly lower antibody and INF-γ response compared to responder HD patients and controls even after the 3D. A new strategy is needed to protect low/non-responder HD patients from severe SARS-CoV-2 infection.

[10 Years Accountable Care Organizations in the USA: Impulses for Health Care Reform in Germany?] / 10 Jahre Accounable Care Organizations in den USA: Impulse für Reformen in Deutschland?

GOAL OF THE STUDY: An intent of the Patient Protection and Affordable Care Acts (ACA), also know as Obama Care, was to slow the expenditure growth in the public Medicare-System by shifting the accountability for health care outcomes and costs to the provider. For this purpose, provider were allowed to form networks, which would then take accountability for a defined population - Accountable Care Organizations (ACOs). Ten years after the introduction of ACOs, this paper looks at the impact of ACOs both on quality of care and costs of care to assess if ACOs can be a model of care delivery for Germany. METHODS: In a mixed-method approach, a rapid review was conducted in Health System Evidence and PubMed. This was supported with further papers identified using the snowballing-technique. After screening the abstracts, we included articles containing information on cost- and/or quality impact of US-Medicare-ACOs. The findings of the rapid review were challenged with 16 ACO-experts and stakeholder in the USA. RESULTS: In total, we included 60 publications which incorporated 6 reports that were either conducted directly by governmental institutions or ordered by them, along with 3 previous reviews. Among these, 31 contained information on costs of care, 18 contained information on quality of care and 11 had information on both aspects. The publications show that ACOs reduced costs of of care. Cost reductions were achieved compared to historic costs, to populations not cared for in ACOs, and counterfactuals. Quality of care stayed the same or improved. CONCLUSION: ACOs contributed to slowing the cost growth in US Medicare without compromising quality of care. Thus, a transferal of this model of care to Germany should be considered. However, various policies have led to ACOs failing to unleash their full potential. Against this background, and against the background of stark differences between US Medicare and the German health care system, a critical reflection of the necessary policies underlying ACOs-like structures in Germany, needs to be undertaken.

Haemodialysis patients show a highly diminished antibody response after COVID-19 mRNA vaccination compared with healthy controls.

BACKGROUND: Haemodialysis (HD) patients are exposed to a high risk due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. They are prone to acquiring the infection and are threatened by high mortality rates in case of infection. However, HD patients were not included in the efficacy trials of the SARS-CoV-2 vaccines. Such efficacy data would have been critical because HD patients show decreased responses against various other vaccines and this could translate to the SARS-CoV-2 vaccines as well. METHODS: We conducted a prospective cohort study that contained a group of 81 HD patients and 80 healthy controls. All of them had been vaccinated with the BioNTech/Pfizer mRNA vaccine (two doses, as per the manufacturer's recommendation). The anti-SARS-CoV-2 spike (S) antibody response was measured for all participants 21 days after the second dose. The groups were compared using univariate quantile regressions and a multivariate analysis. The adverse events (AEs) of the vaccination were assessed via a questionnaire. Finally, a correlation between the HBs-antibody response and the SARS-CoV-2 antibody response in the HD patients was established. RESULTS: The HD patients had significantly lower anti-SARS-CoV-2 S antibody titres than the control patients 21 days after vaccination (median was 171 U/mL for dialysis patients and 2500 U/mL for the controls). Further, the HD group presented fewer AEs than the control group. No correlation was found between the antibody response to previous Hepatitis B vaccination and that of the SARS-CoV-2 vaccine. CONCLUSIONS: HD patients present highly diminished SARS-CoV-2 S antibody titres compared with a cohort of controls. Therefore, they could be much less protected by SARS-CoV-2 mRNA vaccinations than expected. Further studies to test alternative vaccination schemes should be considered.

Structure of colloidal gels at intermediate concentrations: the role of competing interactions.

Colloidal gels formed by colloid-polymer mixtures with an intermediate volume fraction (ϕc ≈ 0.4) are investigated by confocal microscopy. In addition, we have performed Monte Carlo simulations based on a simple effective pair potential that includes a short-range attractive contribution representing depletion interactions, and a longer-range repulsive contribution describing the electrostatic interactions due to the presence of residual charges. Despite neglecting non-equilibrium effects, experiments and simulations yield similar gel structures, characterised by, e.g., the pair, angular and bond distribution functions. We find that the structure hardly depends on the strength of the attraction if the electrostatic contribution is fixed, but changes significantly if the electrostatic screening is changed. This delicate balance between attractions and repulsions, which we quantify by the second virial coefficient, also determines the location of the gelation boundary.

Subclass-specific antibody responses to human cytomegalovirus in lung transplant recipients and their association with constant heavy immunoglobulin G chain polymorphism and virus replication.

BACKGROUND: Human cytomegalovirus (HCMV) causes severe infections in transplant recipients. The significance of the HCMV-specific antibody (Ab) response in limiting HCMV replication is not clear. Therefore, we analyzed the HCMV-specific subclass Ab profile in lung transplant recipients (LTRs) and its association with the genomic immunoglobulin G (IgG) heavy-chain variants GM3/17 and HCMV DNAemia. METHODS: We determined HCMV-specific total IgG, IgG1 and IgG3 Ab levels by enzyme-linked immunoassay and HCMV-DNAemia by quantitative polymerase chain reaction during post-transplant follow-up in 57 LTRs and, in 44 of these recipients, the genetic allotype marker 359a/g variants (reflecting GM3/17 allotypes) by genotyping. RESULTS: In seropositive LTRs there was a significant Ab response to HCMV viremia (p = 0.0005), especially when low HCMV DNA levels were detected (<1,000 copies/ml: p = 0.0012; DNAemia >1,000 copies/ml: p = 0.0516). In particular, IgG3 but not IgG1, increased with viremia (IgG3: p = 0.0004). IgG1 levels were significantly lower in patients with 359 g/g (GM3/3) than in those with 359 a/g (GM3/17) variant (p < 0.0001). Of note, the IgG3 increase with viremia occurred particularly in patients carrying the IgG1 low-level 359 g/g variant (p < 0.0002). CONCLUSION: These data suggest that the HCMV-specific Ab response, and especially the IgG3 subclass response, correlate significantly with HCMV replication after transplantation. The patients' GM 3/17 variant is significantly associated with their HCMV IgG subclass profile.

Evaluation of a multiplex ligation-dependent probe amplification assay for the detection of respiratory pathogens in oncological patients.

BACKGROUND: Respiratory tract infections are widespread and may cause significant morbidity and mortality in immunosuppressed populations such as oncological patients. OBJECTIVES: The RealAccurate Respiratory RT PCR Kit covering 14 respiratory viruses was compared to the RespiFinder Smart22, a broad-spectrum multiplex ligation-dependent probe amplification (MLPA) test, targeting 22 viral and bacterial respiratory pathogens. STUDY DESIGN: After verification of its analytical performance, the clinical performance of the RespiFinder Smart22 was evaluated by re-analysis of 96 respiratory samples from oncological patients. Additionally, the time to result (TTR) of both methods was compared. RESULTS: The analytical performance of the RespiFinder Smart22 fulfilled all previously specified criteria. Concordant results in both assays were achieved in 74.0% of all clinical specimens and in 91.2% when only positive results were taken into account. The RespiFinder Smart22 yielded additional results in a total of 22 (22.9% of 96) samples due to higher test sensitivity and a broader, highly multiplexed spectrum of pathogens. The TTR of a typical routine test consisting of three samples were 206 and 356 min for the RealAccurate Respiratory RT PCR Kit and the RespiFinder Smart22, respectively. However, hands-on time was reduced by 59.0% applying the MLPA method. CONCLUSIONS: In our hands, the RespiFinder Smart22 showed excellent analytical performance while hands-on time was halved in comparison to the RT PCR method. Regarding the clinical evaluation, the MLPA method provided additional results in 22.9% (22/96) of specimens due to its comprehensive format, higher test sensitivity and the capability to detect 22 pathogens compared to 14 with the RealAccurate Respiratory RT PCR Kit.

Association of HCMV specific IgG subclass antibody levels with gender and age.

Infection with human cytomegalovirus (HCMV), a ubiquitously distributed herpesvirus, has been associated with human immune system aging. Especially total HCMV specific IgG antibody (AB) titres have been correlated with human frailty and mortality. The aim of this study was to further assess to which extent HCMV specific subclass AB titres differ between individuals and whether this is associated with age and gender. ELISA tests detecting HCMV specific IgG subclass 1 and 3 ABs, the main subclass ABs directed against HCMV, were developed. Using these ELISAs, 145 (73 female and 72 male) age-matched patients, aged 17 to 87 years, were tested. The results showed that the IgG1 and 3 subclass distribution was highly variable among individuals, and that female persons had significantly higher IgG3 titres than age-matched male persons (p=0.0073). A correlation of the IgG3 subclass titres with age was found in female persons (Spearman r=0.305, p=0.0088). Thus the total HCMV specific IgG level appears to consist of a variable and gender associated distribution of IgG subclass ABs developed against persistent HCMV infection. The analysis of IgG subclass titres therefore could further be used to refine previously established clinical associations of aging with total HCMV specific IgG AB titres.

Analysis of mutations in the S gene of hepatitis B virus strains in patients with chronic infection by online bioinformatics tools.

Hepatitis B virus (HBV) genomes show a high rate of mutations. This can lead to a variety of amino acid changes in the surface and polymerase genes, causing changes in viral protein conformation that can result in diminished antibody binding or decreased secretion of surface antigen (HBsAg). HBV monitoring increasingly relies on HBsAg detection and quantification, and therefore epidemiological data on HBsAg mutations are needed. We therefore analyzed the frequency of HBsAg mutations possibly influencing the quantification of HBsAg (MUPIQHs) in an unselected patient collective. To this end, we determined the HBV surface and polymerase gene sequences of an unselected patient collective of 237 individuals chronically infected with HBV and analyzed the MUPIQHs in these sequences using three different online HBV sequence analysis tools. We found that 17 or 34% of the patients, depending on the online interpretation algorithm used, harbored MUPIQHs and that MUPIQHs were not significantly associated with the duration of disease, treatment, or HBV genotype. Thus, this study shows that a substantial amount of HBV sequences derived from unselected patients chronically infected with HBV carry MUPIQHs, and therefore the reliability of routine quantitative and qualitative HBsAg tests needs to be reevaluated.

HIV coreceptor tropism in antiretroviral treatment-naive patients newly diagnosed at a late stage of HIV infection.

OBJECTIVE: A substantial number of HIV infections worldwide are diagnosed at a late stage of disease. Mortality in late presenters is high, and their treatment is a specific challenge. We have determined the relative proportions of HIV-1 strains of different coreceptor tropism (CRT) in this group of patients and investigated the impact of CRT on progression markers such as CD4 cell counts and viral load, and on the clinical presentation of the patients. DESIGN AND METHODS: Plasma samples from 50 treatment-naive patients with a late HIV diagnosis (CD4 cell counts of <200 cells/microl at the time of diagnosis) were analyzed. HIV strains were sequenced, and for CRT determination, the internet tool geno2pheno[coreceptor] was used, with a 20% false-positive rate as the cutoff. Differences in progression markers, patient characteristics and HIV subtype distribution between the R5-infected and X4/DM-infected patient groups were evaluated statistically. RESULTS: CRT predictions indicated that 62% of the patients had only R5-tropic strains. CRT was not associated with CD4 cell counts or viral load at the time of diagnosis. Only in very late presenters (CD4 cell counts <50 cells/microl) was there a significant difference in disease stage at the time of presentation, showing that patients with R5 more often were at Centers for Disease Control and Prevention stage C3 compared with those with X4/DM strains (P = 0.04). CONCLUSION: A substantial number of patients diagnosed at a late stage of HIV-1 infection may be infected exclusively with R5-tropic virus strains, making this specific patient group a possible candidate for coreceptor antagonist treatment.