[Evaluating the introduction of HIV pre-exposure prophylaxis as a benefit of statutory health insurance (EvE-PrEP) : Highly effective protection against HIV without an increase in sexually transmitted infections]. / Evaluation der Einführung der HIV-Präexpositionsprophylaxe als Leistung der gesetzlichen Krankenversicherung (EvE­PrEP) : Hocheffektiver Schutz vor HIV und keine Zunahme von sexuell übertragbaren Infektionen.

BACKGROUND: We investigated the impact of HIV pre-exposure prophylaxis (PrEP) as a new service of the statutory health insurance (SHI) on the incidence of HIV and other sexually transmitted infections (STIs) in Germany. In addition, PrEP needs and access barriers were analyzed. METHODS: The following data were evaluated as part of the evaluation project: HIV and syphilis notification data and extended surveillance by the Robert Koch Institute (RKI), pharmacy prescription data, SHI routine data, PrEP use in HIV-specialty care centers, Checkpoint, the BRAHMS and PrApp studies, as well as a community board. RESULTS: The majority of PrEP users were male (98-99%), primarily aged between 25-45 years, and predominantly of German nationality or origin (67-82%). The majority were men who have sex with men (99%). With regard to HIV infections, PrEP proved to be highly effective. There were only isolated cases of HIV infections (HIV incidence rate 0.08/100 person years); in most cases the suspected reason was low adherence. The incidences of chlamydia, gonorrhea, and syphilis did not increase but remained almost the same or even decreased. A need for information on PrEP for people in trans*/non-binary communities, sex workers, migrants, and drug users emerged. Needs-based services for target groups at increased risk of HIV are necessary. DISCUSSION: PrEP proved to be a very effective HIV prevention method. The partly feared indirect negative influences on STI rates were not confirmed in this study. Due to the temporal overlap with the containment measures during the COVID-19 pandemic, a longer observation period would be desirable for a conclusive assessment.

Smartphone-assisted training with education for patients with hip and/or knee osteoarthritis (SmArt-E): study protocol for a multicentre pragmatic randomized controlled trial.

INTRODUCTION: Hip and knee osteoarthritis are associated with functional limitations, pain and restrictions in quality of life and the ability to work. Furthermore, with growing prevalence, osteoarthritis is increasingly causing (in)direct costs. Guidelines recommend exercise therapy and education as primary treatment strategies. Available options for treatment based on physical activity promotion and lifestyle change are often insufficiently provided and used. In addition, the quality of current exercise programmes often does not meet the changing care needs of older people with comorbidities and exercise adherence is a challenge beyond personal physiotherapy. The main objective of this study is to investigate the short- and long-term (cost-)effectiveness of the SmArt-E programme in people with hip and/or knee osteoarthritis in terms of pain and physical functioning compared to usual care. METHODS: This study is designed as a multicentre randomized controlled trial with a target sample size of 330 patients. The intervention is based on the e-Exercise intervention from the Netherlands, consists of a training and education programme and is conducted as a blended care intervention over 12 months. We use an app to support independent training and the development of self-management skills. The primary and secondary hypotheses are that participants in the SmArt-E intervention will have less pain (numerical rating scale) and better physical functioning (Hip Disability and Osteoarthritis Outcome Score, Knee Injury and Osteoarthritis Outcome Score) compared to participants in the usual care group after 12 and 3 months. Other secondary outcomes are based on domains of the Osteoarthritis Research Society International (OARSI). The study will be accompanied by a process evaluation. DISCUSSION: After a positive evaluation, SmArt-E can be offered in usual care, flexibly addressing different care situations. The desired sustainability and the support of the participants' behavioural change are initiated via the app through audio-visual contact with their physiotherapists. Furthermore, the app supports the repetition and consolidation of learned training and educational content. For people with osteoarthritis, the new form of care with proven effectiveness can lead to a reduction in underuse and misuse of care as well as contribute to a reduction in (in)direct costs. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00028477. Registered on August 10, 2022.

Generalizability and reach of a randomized controlled trial to improve oral health among home care recipients: comparing participants and nonparticipants at baseline and during follow-up.

BACKGROUND: The generalizability of randomized controlled trials (RCTs) with a low response can be limited by systematic differences between participants and nonparticipants. This participation bias, however, is rarely investigated because data on nonparticipants is usually not available. The purpose of this article is to compare all participants and nonparticipants of a RCT to improve oral health among home care recipients at baseline and during follow-up using claims data. METHODS: Seven German statutory health and long-term care insurance funds invited 9656 home care recipients to participate in the RCT MundPflege. Claims data for all participants (n = 527, 5.5% response) and nonparticipants (n = 9129) were analyzed. Associations between trial participation and sex, age, care dependency, number of Elixhauser diseases, and dementia, as well as nursing, medical, and dental care utilization at baseline, were investigated using multivariable logistic regression. Associations between trial participation and the probability of (a) moving into a nursing home, (b) being hospitalized, and (c) death during 1 year of follow-up were examined via Cox proportional hazards regressions, controlling for baseline variables. RESULTS: At baseline, trial participation was positively associated with male sex (odds ratio 1.29 [95% confidence interval 1.08-1.54]), high (vs. low 1.46 [1.15-1.86]) care dependency, receiving occasional in-kind benefits to relieve caring relatives (1.45 [1.15-1.84]), having a referral by a general practitioner to a medical specialist (1.62 [1.21-2.18]), and dental care utilization (2.02 [1.67-2.45]). It was negatively associated with being 75-84 (vs. < 60 0.67 [0.50-0.90]) and 85 + (0.50 [0.37-0.69]) years old. For morbidity, hospitalizations, and formal, respite, short-term, and day or night care, no associations were found. During follow-up, participants were less likely to move into a nursing home than nonparticipants (hazard ratio 0.50 [0.32-0.79]). For hospitalizations and mortality, no associations were found. CONCLUSIONS: For half of the comparisons, differences between participants and nonparticipants were observed. The RCT's generalizability is limited, but to a smaller extent than one would expect because of the low response. Routine data provide a valuable source for investigating potential differences between trial participants and nonparticipants, which might be used by future RCTs to evaluate the generalizability of their findings. TRIAL REGISTRATION: German Clinical Trials Register DRKS00013517 . Retrospectively registered on June 11, 2018.

Effectiveness of a Dental Intervention to Improve Oral Health among Home Care Recipients: A Randomized Controlled Trial.

We quantified the effectiveness of an oral health intervention among home care recipients. Seven German insurance funds invited home care recipients to participate in a two-arm randomized controlled trial. At t0, the treatment group (TG) received an intervention comprising an oral health assessment, dental treatment recommendations and oral health education. The control group (CG) received usual care. At t1, blinded observers assessed objective (Oral Health Assessment Tool (OHAT)) and subjective (Oral Health Impact Profile (OHIP)) oral health and the objective periodontal situation (Periodontal Screening Index (PSI)). Of 9656 invited individuals, 527 (5.5%) participated. In the TG, 164 of 259 (63.3%) participants received the intervention and 112 (43.2%) received an outcome assessment. In the CG, 137 of 268 (51.1%) participants received an outcome assessment. The OHAT mean score (2.83 vs. 3.31, p = 0.0665) and the OHIP mean score (8.92 vs. 7.99, p = 0.1884) did not differ significantly. The prevalence of any periodontal problems (77.1% vs. 92.0%, p = 0.0027) was significantly lower in the TG than in the CG, but the prevalence of periodontitis was not (35.4% vs. 44.6%, p = 0.1764). Future studies should investigate whether other recruitment strategies and a more comprehensive intervention might be more successful in improving oral health among home care recipients.

Home care recipients have poorer oral health than nursing home residents: Results from two German studies.

OBJECTIVES: To describe and compare the objective and subjective oral health of older nursing home residents and home care recipients, and to investigate whether oral health is associated with sociodemographic characteristics and the long-term care (LTC) setting. METHODS: In two German studies, the oral health of 246 nursing home residents and 90 home care recipients aged ≥60 years was assessed objectively using the Oral Health Assessment Tool (OHAT) and subjectively using the Oral Health Impact Profile (OHIP). OHAT and OHIP scores were compared between both settings. Multivariable logistic regressions were applied to investigate whether oral health is associated with sex, age group, LTC grade, and LTC setting. RESULTS: OHAT and OHIP mean scores in the home care setting were higher compared to the nursing home setting (OHAT: 3.13 vs. 1.28, p < .0001; OHIP: 7.81 vs. 2.15, p < .0001). The adjusted odds ratios for poor objective and subjective oral health for home care recipients vs. nursing home residents were 6.71 (95 % confidence interval 3.29-13.69) and 4.92 (2.77-8.76). No significant associations with sociodemographic characteristics were found. CONCLUSIONS: Oral health was poor in both settings, but home care recipients were more likely to have poor oral health than nursing home residents. Interventions to improve oral health are needed in the nursing home setting and, even more importantly, in the home care setting. CLINICAL SIGNIFICANCE: Oral health among older people in need of LTC is poor and should be improved. From a health policy perspective, home care recipients may need more attention.

Differences in medical specialist utilization among older people in need of long-term care - results from German health claims data.

BACKGROUND: Elderly in need of long-term care tend to have worse health and have higher need of medical care than elderly without need for long-term care. Yet, characteristics associated with long-term care need can impede health care access: Higher levels of long-term care need come with physical and cognitive decline such as frailty and memory loss. Yet, it has not been investigated whether level of long-term care need is related to medical care utilization. METHODS: We investigated the association between the level of long-term care and medical specialist utilization among nursing home residents and home care recipients. We applied zero-inflated Poisson regression with robust standard errors based on a sample of statutory health insurance members. The sample consisted of 100.000 elderly over age 60. We controlled for age, gender, morbidity and mortality, residential density, and general practitioner utilization. RESULTS: We found a strong gradient effect of the level of long-term care for 9 out of 12 medical specialties: A higher level of long-term care need was associated with a lower probability of having a medical specialist visit. Yet, we did not find clear effects of the level of long-term care need on the intensity of medical specialist care. These findings were similar for both the nursing home and home care setting. CONCLUSION: The findings indicate that inequalities in medical specialist utilization exist between elderly with differing levels of long-term care need because differences in morbidity were controlled for. Elderly with higher need of long-term care might face more access barriers to specialist medical care.

Needs-based provision of medical care to nursing home residents: protocol for a mixed-methods study.

INTRODUCTION: Nursing home residents typically have greater needs for medical care than community-dwelling elderly. However, restricted cognitive abilities and limited mobility may impede their access to general practitioners and medical specialists. The provision of medical care in nursing homes may therefore be inappropriate in some areas of medical care. The purpose of this mixed-methods study is to systematically assess, evaluate and explain met and unmet medical care needs in German nursing homes and to develop solutions where medical care is found to be inappropriate. METHODS AND ANALYSIS: First, statutory health insurance claims data are analysed to identify differences in the utilisation of medical care between nursing home residents and community-dwelling elderly with and without need for long-term care. Second, the health status and medical care of 500 nursing home residents are assessed and evaluated to quantify met and unmet medical care needs. Third, qualitative expert interviews and case conferences and, fourth, quantitative analyses of linked data are used to provide structural, case-specific and generalisable explanations of inappropriate medical care among nursing home residents. Fifth, a modified Delphi study is employed to develop pilot projects aiming to improve medical care in nursing homes. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the University of Bremen on 23 November 2017. Research findings are disseminated through presentations at national and international conferences and publications in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: DRKS00012383.

Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis.

The guanylate-binding proteins (GBPs) form a group of interferon-gamma inducible GTP-binding proteins which belong to the family of dynamin-related proteins. Like other members of this family, human guanylate-binding protein 1 (hGBP1) shows nucleotide-dependent oligomerisation that stimulates the GTPase activity of the protein. A unique feature of the GBPs is their ability to hydrolyse GTP to GDP and GMP. In order to elucidate the relationship between these findings, we designed point mutants in the phosphate-binding loop (P-loop) as well as in the switch I and switch II regions of the protein based on the crystal structure of hGBP1. These mutant proteins were analysed for their interaction with guanine nucleotides labeled with a fluorescence dye and for their ability to hydrolyse GTP in a cooperative manner. We identified mutations of amino acid residues that decrease GTPase activity by orders of magnitude a part of which are conserved in GTP-binding proteins. In addition, mutants in the P-loop were characterized that strongly impair binding of nucleotide. In consequence, together with altered GTPase activity and given cellular nucleotide concentrations this results in hGBP1 mutants prevailingly resting in the nucleotide-free (K51A and S52N) or the GTP bound form (R48A), respectively. Using size-exclusion chromatography and analytical ultracentrifugation we addressed the impact on protein oligomerisation. In summary, mutants of hGBP1 were identified and biochemically characterized providing hGBP1 locked in defined states in order to investigate their functional role in future cell biology studies.

Mouse CD99 participates in T-cell recruitment into inflamed skin.

Human CD99 is a small highly O-glycosylated cell-surface protein expressed on most leukocytes. It was recently found to be expressed at endothelial cell contacts and to participate in the transendothelial migration (TEM) of monocytes in vitro. In order to analyze the physiologic relevance of CD99 in vivo we searched for the mouse homolog. We cloned a mouse cDNA coding for a protein 45% identical in its sequence with human CD99. Based on the cDNA, we generated antibodies against this mouse homolog of CD99, which detected the antigen on most leukocytes, on endothelia of various tissues, and at cell contacts of cultured endothelial cells. Cell aggregation of CD99-transfected Chinese hamster ovary (CHO) cells was completely blocked by anti-CD99 antibodies. The same antibodies inhibited TEM of lymphocytes in vitro, independent of whether T cells or endothelial cells were preincubated with antibodies. In a cutaneous delayed-type hypersensitivity (DTH) reaction, anti-CD99 antibodies inhibited the recruitment of in vivo-activated T cells into inflamed skin as well as edema formation. We conclude that mouse CD99 participates in the TEM of lymphocytes and in their recruitment to inflamed skin in vivo. This establishes CD99 as a valid target for interference with cutaneous inflammatory processes.

VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts.

VE-cadherin is the essential adhesion molecule in endothelial adherens junctions, and the regulation of protein tyrosine phosphorylation is thought to be important for the control of adherens junction integrity. We show here that VE-PTP (vascular endothelial protein tyrosine phosphatase), an endothelial receptor-type phosphatase, co-precipitates with VE-cadherin, but not with beta-catenin, from cell lysates of transfected COS-7 cells and of endothelial cells. Co-precipitation of VE-cadherin and VE-PTP required the most membrane-proximal extracellular domains of each protein. Expression of VE-PTP in triple-transfected COS-7 cells and in CHO cells reversed the tyrosine phosphorylation of VE-cadherin elicited by vascular endothelial growth factor receptor 2 (VEGFR-2). Expression of VE-PTP under an inducible promotor in CHO cells transfected with VE-cadherin and VEGFR-2 increased the VE-cadherin-mediated barrier integrity of a cellular monolayer. Surprisingly, a catalytically inactive mutant form of VE-PTP had the same effect on VE-cadherin phosphorylation and cell layer permeability. Thus, VE-PTP is a transmembrane binding partner of VE-cadherin that associates through an extracellular domain and reduces the tyrosine phosphorylation of VE-cadherin and cell layer permeability independently of its enzymatic activity.