Impact of digital services on healthcare and social welfare: An umbrella review.

BACKGROUND: Digital services can be effective and cost-efficient options for treating non-communicable diseases, but generalizability is limited due to heterogeneous treatment effects. This umbrella review aims to evaluate the impact of digital services on population health, costs, and patient and healthcare professional satisfaction, and to identify facilitators and barriers to using digital services in healthcare and social welfare. METHODS: The protocol of the study was registered on the 4th of September 2022 to the International Prospective Register of Systematic Reviews, PROSPERO (CRD42022355635). The review was performed using the Centre for Reviews and Dissemination, Cochrane, Ovid Medline, Scopus, and Web of Science in June 2022. The methodological quality of the included reviews was assessed. The impact of digital services was categorized as no evidence, no dominance, and mixed and positive effect. Inductive content analysis was used to identify facilitators and barriers. RESULTS: A total of 66 studies were included in the review, 64 % of which were evaluated as high quality. Studies on the impact of digital services in social welfare were not identified. Sixty-five percent of reviews evaluated the impact of digital services on population health with mixed effects; 21 % were on costs with mixed effects; 27 % were on patient satisfaction with positive effects; and 7.6 % were on healthcare professionals' satisfaction with mixed effects. Various features, allocation, end-user support, organized services, and service development facilitated the use of digital services. Correspondingly, barriers were related to service limitations, digital competency, funding- and service strategies, resources and change management. CONCLUSIONS: Compared to usual care, digital services had a mixed impact on population health and costs with high satisfaction in patients. Mixed healthcare professionals' satisfaction was associated with the use of digital services, and it was less studied. To ensure successful implementation and sustainability of digital services, attention must be paid to address barriers and supporting facilitators at all levels.

Effectiveness of Telemonitoring in Reducing Hospitalization and Associated Costs for Patients With Heart Failure in Finland: Nonrandomized Pre-Post Telemonitoring Study.

BACKGROUND: Many patients with chronic heart failure (HF) experience a reduced health status, leading to readmission after hospitalization despite receiving conventional care. Telemonitoring approaches aim to improve the early detection of HF decompensations and prevent readmissions. However, knowledge about the impact of telemonitoring on preventing readmissions and related costs remains scarce. OBJECTIVE: This study assessed the effectiveness of adding a telemonitoring solution to the standard of care (SOC) for the prevention of hospitalization and related costs in patients with HF in Finland. METHODS: We performed a nonrandomized pre-post telemonitoring study to estimate health care costs and resource use during 6 months on SOC followed by 6 months on SOC with a novel telemonitoring solution. The telemonitoring solution consisted of a digital platform for patient-reported symptoms and daily weight and blood pressure measurements, automatically generated alerts triggering phone calls with secondary care nurses, and rapid response to alerts by treating physicians. Telemonitoring solution data were linked to patient register data on primary care, secondary care, and hospitalization. The patient register of the Southern Savonia Social and Health Care Authority (Essote) was used. Eligible patients had at least 1 hospital admission within the last 12 months and self-reported New York Heart Association class II-IV from the central hospital in the Southern Savonia region. RESULTS: Out of 50 recruited patients with HF, 43 completed the study and were included in the analysis. The hospitalization-related cost decreased (49%; P=.03) from €2189 (95% CI €1384-€2994; a currency exchange rate of EUR €1=US $1.10589 is applicable) during SOC to €1114 (95% CI €425-€1803) during telemonitoring. The number of patients with at least 1 hospitalization due to HF was reduced by 70% (P=.002) from 20 (47%) out of 43patients during SOC to 6 (14%) out of 43 patients in telemonitoring. The estimated mean total health care cost per patient was €3124 (95% CI €2212-€4036) during SOC and €2104 (95% CI €1313-€2895) during telemonitoring, resulting in a 33% reduction (P=.07) in costs with telemonitoring. CONCLUSIONS: The results suggest that the telemonitoring solution can reduce hospital-related costs for patients with HF with a recent hospital admission.

Predictive factors for prolonged sick leave in breast cancer patients treated with adjuvant therapies: a retrospective registry study.

BACKGROUND: Being able to work during and after breast cancer treatments is important for patients to have a sense of normalcy, financial security, and improved quality of life, and for society due to the economic burden of sick leave. Factors influencing the length of sick leave can be sociodemographic factors, workplace adaptations, recurrences, symptoms, and type of treatment. The aim of this study is to analyse factors associated with prolonged sick leave after adjuvant breast cancer treatments. METHODS: The population of this registry study consists of 1333 early breast cancer patients diagnosed and treated in Helsinki University Hospital between 2016 and 2018. Data on patient demographics, disease characteristics, treatment, and healthcare resource utilization were obtained from Helsinki University Hospital and data on income level and sick leave were obtained from Kela sickness benefits registry. Prolonged sick leave was determined as the patient accumulating 30 or more reimbursed sick leave days during a 60-day follow-up period after the end of active oncological treatment. Univariate analysis and multivariate analysis were conducted. RESULTS: A total of 26% of the patients in this study were on sick leave for 30 or more days after the active treatments ended. Study findings show that chemotherapy, triple-negative breast cancer, reconstructive surgery, amount of outpatient visits, and income are associated with prolonged sick leave. Independent predictors of prolonged sick leave were treatment line, number of outpatient contacts, reconstruction, and triple-negative breast cancer. CONCLUSIONS: Our study shows that prolonged sick leave affects a substantial number of working-age women with early breast cancer. Independent predictors for prolonged sick leave were all treatment-related. Targeted support for treatment-related side-effects already during the treatment period could lead to better recovery and earlier return to work.

Signaling pathways in human osteoclasts differentiation: ERK1/2 as a key player.

Little is known about the signaling pathways involved in the differentiation of human osteoclasts. The present study evaluated the roles of the Ras/PI3K/Akt/mTOR, Ras/Raf/MEK1/2/ERK1/2, calcium-PKC, and p38 signaling pathways in human osteoclast differentiation. Mononuclear cells were isolated from the peripheral blood of control persons and patients with neurofibromatosis 1 (NF1), and the cells were differentiated into osteoclasts in the presence of signaling pathway inhibitors. Osteoclast differentiation was assessed using tartrate-resistant acid phosphatase 5B. Inhibition of most signaling pathways with chemical inhibitors decreased the number of human osteoclasts and disrupted F-actin ring formation, while the inhibition of p38 resulted in an increased number of osteoclasts, which is a finding contradictory to previous murine studies. However, the p38 inhibition did not increase the bone resorption capacity of the cells. Ras-inhibitor FTS increased osteoclastogenesis in samples from control persons, but an inhibitory effect was observed in NF1 samples. Inhibition of MEK, PI3K, and mTOR reduced markedly the number of NF1-deficient osteoclasts, but no effect was observed in control samples. Western blot analyses showed that the changes in the phosphorylation of ERK1/2 correlated with the number of osteoclasts. Our results highlight the fact that osteoclastogenesis is regulated by multiple interacting signaling pathways and emphasize that murine and human findings related to osteoclastogenesis are not necessarily equivalent.

Circulating free DNA in the plasma of individuals with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant syndrome whose characteristic manifestations include benign neurofibromas, yet NF1 is also associated with a high risk of cancer. Measurements of circulating free plasma DNA (cfDNA) are gaining wider applicability in cancer diagnostics, targeting of therapy, and monitoring of therapeutic response. Individuals with NF1 are likely to be followed up using this method, but the effects of NF1 and neurofibromas on cfDNA levels are not known. We studied peripheral blood samples from 19 adults with NF1 and 12 healthy controls. The cfDNA was isolated from plasma with QIAamp Circulating Nucleic Acid Kit and quantified using the Qubit 2.0 Fluorometer. The cfDNA concentration of each sample was normalized relative to the plasma protein concentration. The normalized median concentration of cfDNA in plasma was 19.3 ng/ml (range 6.6-78.6) among individuals with NF1 and 15.9 ng/ml (range 4.8-47.0) among controls (p = .369). Individuals with NF1 who also had plexiform neurofibroma (pNF) showed non-significantly elevated cfDNA concentration compared to individuals with NF1 and without known pNF (median 25.4 vs. 18.8 ng/ml, p = .122). The effect of NF1 on cfDNA seems to be relatively small and NF1 is therefore unlikely to hamper the use of cfDNA-based assays.

The effect of estradiol, testosterone, and human chorionic gonadotropin on the proliferation of Schwann cells with NF1 +/- or NF1 -/- genotype derived from human cutaneous neurofibromas.

Dermal neurofibromas are the hallmarks of neurofibromatosis type 1 (NF1). Neurofibromas harbor Schwann cells with two different genotypes: Schwann cells which carry the germline mutation and a healthy NF1 allele (NF1 +/-), and a subpopulation of Schwann cells which harbor the so-called second hit leading to inactivation of both NF1 alleles (NF1 -/-). The second hit in the NF1 gene of Schwann cells is considered to be the initial step in the development of neurofibromas. Dermal neurofibromas typically start to grow in puberty, and their number and size increase during pregnancy, indicating hormone responsiveness. This is the first study to address the effect of human chorionic gonadotropin (hCG) on the proliferation of human NF1 +/- and NF1 -/- Schwann cells in vitro. In addition, the effects of estradiol and testosterone were also investigated. The results showed that NF1 -/- Schwann cells were more sensitive to estradiol, testosterone, and human chorionic gonadotropin than NF1 +/- cells. Specifically, the proliferation of NF1 -/- Schwann cells was increased by up to 99, 110, and 170% compared to vehicle control when treated with estradiol, testosterone, and hCG, respectively. Interestingly, no effect of estradiol, testosterone, or hCG on the proliferation of the cells with NF1 +/- genotype was observed. To conclude, the somatic second hit in the NF1 gene sensitizes Schwann cells to sex hormones resulting in a highly increased proliferation. Our results highlight the significance of sex hormones in the regulation of neurofibroma growth.

Diversity of actin architecture in human osteoclasts: network of curved and branched actin supporting cell shape and intercellular micrometer-level tubes.

Osteoclasts are multinucleated bone-resorbing cells with a dynamic actin cytoskeleton. Osteoclasts are derived from circulating mononuclear precursors. Confocal and stimulated emission depletion (STED) super-resolution microscopy was used to investigate peripheral blood-derived human osteoclasts cultured on glass surfaces. STED and confocal microscopy demonstrated that the actin was curved and branched, for instance, in the vicinity of membrane ruffles. The overall architecture of the curved actin network extended from the podosomes to the top of the cell. The other novel finding was that a micrometer-level tube containing actin bridged the osteoclasts well above the level of the culture glass. The actin filaments of the tubes originated from the network of curved actin often surrounding a group of nuclei. Furthermore, nuclei were occasionally located inside the tubes. Our findings demonstrated the accumulation of c-Src, cortactin, cofilin, and actin around nuclei suggesting their role in nuclear processes such as the locomotion of nuclei. ARP2/3 labeling was abundant at the substratum level of osteoclasts and in the branched actin network, where it localized to the branching points. We speculate that the actin-containing tubes of osteoclasts may provide a means of transportation of nuclei, e.g., during the fusion of osteoclasts. These novel findings can pave the way for future studies aiming at the elucidation of the differentiation of multinucleated osteoclasts.

In vitro model of bone to facilitate measurement of adhesion forces and super-resolution imaging of osteoclasts.

To elucidate processes in the osteoclastic bone resorption, visualise resorption and related actin reorganisation, a combination of imaging technologies and an applicable in vitro model is needed. Nanosized bone powder from matching species is deposited on any biocompatible surface in order to form a thin, translucent, smooth and elastic representation of injured bone. Osteoclasts cultured on the layer expressed matching morphology to ones cultured on sawed cortical bone slices. Resorption pits were easily identified by reflectance microscopy. The coating allowed actin structures on the bone interface to be visualised with super-resolution microscopy along with a detailed interlinked actin networks and actin branching in conjunction with V-ATPase, dynamin and Arp2/3 at actin patches. Furthermore, we measured the timescale of an adaptive osteoclast adhesion to bone by force spectroscopy experiments on live osteoclasts with bone-coated AFM cantilevers. Utilising the in vitro model and the advanced imaging technologies we localised immunofluorescence signals in respect to bone with high precision and detected resorption at its early stages. Put together, our data supports a cyclic model for resorption in human osteoclasts.