Spatiotemporal cell landscape of human embryonic tooth development.

Understanding the cellular composition and trajectory of human tooth development is valuable for dentistry and stem cell engineering research. Previous single-cell studies have focused on mature human teeth and developing mouse teeth, but the cell landscape of human embryonic dental development is still unknown. In this study, tooth germ tissues were collected from aborted foetus (17-24 weeks) for single-cell RNA sequence and spatial transcriptome analysis. The cells were classified into seven subclusters of epithelium, and seven clusters of mesenchyme, as well as other cell types such as Schwann cell precursor and pericyte. For epithelium, the stratum intermedium branch and the ameloblast branch diverged from the same set of outer enamel-inner enamel-ALCAM+ epithelial cell lineage, but their spatial distribution of two branches was not clearly distinct. This trajectory received spatially adjacent regulation signals from mesenchyme and pericyte, including JAG1 and APP. The differentiation of pulp cell and pre-odontoblast showed four waves of temporally distinct gene expression, which involved regulation networks of LHX9, DLX5 and SP7, and these genes were regulated by upstream ligands such as the BMP family. This provides a reference landscape for the research on early human tooth development, covering different spatial structures and developmental periods.

Analytical validation of the DropXpert S6 system for diagnosis of chronic myelocytic leukemia.

Digital PCR is a powerful method for absolute nucleic acid quantification and is widely used in the absolute quantification of viral copy numbers, tumor marker detection, and prenatal diagnosis. However, for most of the existing droplet-based dPCR systems, the droplet generation, PCR reaction, and droplet detection are performed separately using different instruments. Making digital PCR both easy to use and practical by integrating the qPCR workflow into a superior all-in-one walkaway solution is one of the core ideas. A new innovative and integrated digital droplet PCR platform was developed that utilizes cutting-edge microfluidics to integrate dPCR workflows onto a single consumable chip. This makes previously complex workflows fast and simple; the whole process of droplet generation, PCR amplification, and droplet detection is completed on one chip, which meets the clinical requirement of "sample in, result out". It provides high multiplexing capabilities and strong sensitivity while all measurements were within the 95% confidence interval. This study is the first validation of the DropXpert S6 system and focuses primarily on verifying its reliability, repeatability, and consistency. In addition, the accuracy, detection limit, linearity, and precision of the system were evaluated after sample collection. Among them, the accuracy assessment by calculating the absolute bias of each target gene yielded a range from -0.1 to 0.08, all within ±0.5 logarithmic orders of magnitude; the LOB for the assay was set at 0, and the LoD value calculated using probit curves is MR4.7 (0.002%); the linearity evaluation showed that the R2 value of the BCR-ABL was 0.9996, and the R2 value of the ABL metrics calculated using the ERM standard was 0.9999; and the precision evaluation showed that all samples had a CV of less than 4% for intra-day, inter-day, and inter-instrument variation. The CV of inter-batch variation was less than 7%. The total CV was less than 5%. The results of the study demonstrate that dd-PCR can be applied to molecular detection and the clinical evaluation of CML patients and provide more precise personal treatment guidance, and its reproducibility predicts the future development of a wide range of clinical applications.

Study on pulp metabolism of patients with pulpitis using ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry.

BACKGROUND AND AIMS: Pulpitis, a pulp disease caused by caries, trauma, and other factors, has a high clinical incidence. This study focused on identifying possible metabolic biomarkers of pulpitis cases and analyzing the related metabolic pathways for providing a theoretical foundation to diagnose and prevent pulpitis. MATERIALS AND METHODS: Pulp samples from 20 pulpitis cases together with 20 normal participants were analyzed with a serum metabolomics approach using ultra-high-performance liquid chromatography (UPLC)/Orbitrap mass spectrometry. Moreover, this work carried out multivariate statistical analysis for screening potential biomarkers of pulpitis. RESULTS: Through biomarker analysis and identification, such as partial least squares discrimination analysis, orthogonal partial least squares discriminant analysis model establishment, correlation analysis, and biomarker pathway analysis, 40 biomarkers associated with 20 metabolic pathways were identified, including 20 upregulated and 20 downregulated metabolites. Those major biomarkers included oxoglutaric acid, inosine, citric acid, and PA(14:1(9Z)/PGD1). Among them, oxoglutaric acid and inosine were most significantly downregulated and had the highest correlation with pulpitis. Among these metabolic pathways, GABAergic synapse and alanine, aspartate, and glutamate metabolism were positively correlated with pulpitis. 4. CONCLUSIONS: These biomarkers as well as metabolic pathways may offer the theoretical foundation to understand pulpitis pathogenesis and develop preventive drugs.

Exosome-targeted delivery of METTL14 regulates NFATc1 m6A methylation levels to correct osteoclast-induced bone resorption.

Osteoporosis has a profound influence on public health. First-line bisphosphonates often cause osteonecrosis of the jaw meanwhile inhibiting osteoclasts. Therefore, it is important to develop effective treatments. The results of this study showed that the increased level of NFATc1 m6A methylation caused by zoledronic acid (ZOL), with 4249A as the functional site, is highly correlated with the decreased bone resorption of osteoclasts. Upstream, METTL14 regulates osteoclast bone absorption through the methylation functional site of NFATc1. Downstream, YTHDF1 and YTHDF2 show antagonistic effects on the post-transcriptional regulation of NFATc1 after the m6A methylation level is elevated by METTL14. In this study, meRIP-Seq, luciferase reporter assays, meRIP and other methods were used to elucidate the NFATc1 regulatory mechanism of osteoclasts from the perspective of RNA methylation. In addition, EphA2 overexpression on exosomes is an effective biological method for targeted delivery of METTL14 into osteoclasts. Importantly, this study shows that METTL14 released by exosomes can increase the m6A methylation level of NFATc1 to inhibit osteoclasts, help postmenopausal osteoporosis patients preserve bone mass, and avoid triggering osteonecrosis of the jaw, thus becoming a new bioactive molecule for the treatment of osteoporosis.

A novel concentrated growth factor (CGF) and bio-oss based strategy for second molar protection after impacted mandibular third molar extraction: a randomized controlled clinical study.

BACKGROUND: The extraction of impacted mandibular third molars might cause large bone defects in the distal area of second molars. A new strategy was innovatively employed here combining autologous bone, Bio-Oss, concentrated growth factors (CGF) gel and CGF membrane for bone repair, and the present study aimed at exploring safety as well as short- and long-term efficacy of this new protocol clinically. MATERIALS AND METHODS: A total of 66 participants were enrolled in this randomized single-blind clinical trial, and randomly allocated to control group (only blood clots), test A group (autogenous bone, Bio-Oss with barrier membrane) and test B group (autogenous bone, Bio-Oss, CGF gel with CGF membrane). The postoperative outcomes including PoSSe scale, periodontal probing depth (PD), degree of gingival recession and computed tomography measurements were assessed at 3rd, 6th, 12th month. A p-value < 0.05 was considered statistically significant. RESULTS: In PoSSe scale, no significant difference was observed except a significant alleviation of early-stage pain perception in test B group (p < 0.05). Also, test B group exhibited better effect on periodontal healing and gingival recession reduction after 6 months (p < 0.05). Both two test groups showed more new bone formation than the control group (p < 0.05). It is noteworthy that the bone repair of test B group was significantly better than that of test A at 3rd and 6th month (p < 0.05), yet no difference was observed at 12th month (p > 0.05). CONCLUSION: Both two test groups could achieve stable long-term efficacy on bone defect repair. The use of CGF gel and CGF membrane could accelerate early-stage bone repair, alleviate short-term pain after surgery, reduce long-term probing depth and relieve economic cost for patients. This new bone repair protocol is worthy of promoting by clinicians. TRIAL REGISTRATION: This study was registered with the identification number ChiCTR2300068466 on 20/02/2023 at Chinese Clinical Trial Registry. Also, it was ethically approved from the institutional ethics committee at the Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (No:2023-010-01), and has been conducted in accordance to the guidelines of the declaration of Helsinki. Written informed consent was obtained from all participants in the study.

Zero-valent iron-peroxydisulfate as synergistic co-milling agents for enhanced mechanochemical destruction of 2,4-dichlorophenol: Coupling reduction with oxidation.

Mechanochemical (MC) remediation with zero-valent iron (ZVI) as co-milling agent enables the non-combustion and solvent-free disposal of solid halogenated organic pollutants (HOPs) via solid-phase reaction, but suffers from incomplete dechlorination (especially for less chlorinated chemicals). Herein, a reduction-oxidation coupling strategy using ZVI and peroxydisulfate as synergistic (ZVI-PDS) co-milling agents was investigated, with 2,4-dichlorophenol (2,4-DCP) as probe contaminant. By revisiting the MC destruction process of 2,4-DCP by ZVI, the contribution of both reductive and oxidative routes is confirmed, and the inefficient •OH generation is addressed. With ball-to-material and reagent-to-pollutant mass ratios of 30:1 and 13:1, respectively, ZVI-PDS achieves higher dechlorination ratio (86.8%) for 2,4-DCP within 5 h, outcompeting sole ZVI (40.3%) or PDS (33.9%), due to the accumulation of numerous SO4•-. As suggested by a two-compartment kinetic model, the optimal ZVI/PDS molar ratio of 4:1 is determined, which balances the relative contribution of reductive/oxidative routes and leads to a maximum mineralization efficiency of 77.4%. The analysis on product distribution verifies the generation of dechlorinated, ring-opening and minor coupling products (with low acute toxicity). This work validates the necessity to couple reduction with oxidation in MC destruction for solid HOPs, and may provide information on reagent formulation.

Ambra1 modulates the sensitivity of mantle cell lymphoma to palbociclib by regulating cyclin D1.

Mantle cell lymphoma (MCL) is a rare B-cell malignancy with a predominantly aggressive clinical course and poor prognosis. Abnormal expression of Ambra1 is closely related to the occurrence and development of various tumors. However, the role of Ambra1 in MCL remains unknown. Here, we performed both in vitro and in vivo experiments to investigate how Ambra1 regulates MCL progression and whether Ambra1 modulates the sensitivity of MCL cells to the CDK4/6 inhibitor palbociclib. We discovered that MCL cells had decreased levels of Ambra1 expression relative to normal B cells. Overexpression of Ambra1 in MCL cells inhibited autophagy, reduced cell proliferation, migration, and invasion, and decreased cyclin D1 level. While knockdown of Ambra1 reduced MCL cell sensitivity to CDK4/6 inhibitor palbociclib. Furthermore, overexpression of cyclin D1 lowered the sensitivity of MCL cells to palbociclib, enhanced cell proliferation, migration, invasion, and autophagy, and inhibited cell apoptosis. When Ambra1 expression was inhibited, the in vivo antitumor effects of palbociclib on MCL were reversed. Ambra1 expression was downregulated but cyclin D1 expression was upregulated in MCL samples, demonstrating a negative correlation between Ambra1 and cyclin D1. Our findings suggest a unique tumor suppressor function for Ambra1 in the development of MCL.

Genome-wide analysis reveals the emergence of multidrug resistant Stenotrophomonas acidaminiphila strain SINDOREI isolated from a patient with sepsis.

Stenotrophomonas acidaminiphila, the most recent reported species in genus Stenotrophomonas, is a relatively rare bacteria and is an aerobic, glucose non-fermentative, Gram-negative bacterium. However, little information of S. acidaminiphila is known to cause human infections. In this research, we firstly reported a multidrug-resistant strain S. acidaminiphila SINDOREI isolated from the blood of a patient with sepsis, who was dead of infection eventually. The whole genome of strain SINDOREI was sequenced, and genome comparisons were performed among six closely related S. acidaminiphila strains. The core genes (2,506 genes) and strain-specific genes were identified, respectively, to know about the strain-level diversity in six S. acidaminiphila stains. The presence of a unique gene (narG) and essential genes involved in biofilm formation in strain SINDOREI are important for the pathogenesis of infections. Strain SINDOREI was resistant to trimethoprim/sulfamethoxazole, ciprofloxacin, ofloxacin, cefepime, ceftazidime, and aztreonam. Several common and specific antibiotic resistance genes were identified in strain SINDOREI. The presence of two sul genes and exclusive determinants GES-1, aadA3, qacL, and cmlA5 is responsible for the resistance to multidrug. The virulence factors and resistance determinants can show the relationship between the phenotype and genotype and afford potential therapeutic strategies for infections.

Metabolomics profiling reveals berberine-inhibited inflammatory response in human gingival fibroblasts by regulating the LPS-induced apoptosis signaling pathway.

This article examines berberine's biological effects and molecular mechanisms with an inflammatory response model induced by lipopolysaccharide (LPS) in human gingival fibroblasts (HGFs) using metabolomics. The viability of HGFs was determined using the cell counting kit-8 (CCK8). ELISA was used to measure inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor- α (TNF-α). An investigation of western blots was conducted to investigate the related proteins of apoptosis. Low concentrations of berberine (0.1, 0.5, and 1 µmol L-1) did not affect HGF growth, whereas high concentrations of berberine (5-25 µmol L-1) significantly activated cell proliferation. Berberine suppressed the elevated secretion of IL-6, IL-1ß, and TNF-α induced by LPS in HGF. Western blot analysis showed that 10 µmol L-1 of berberine significantly inhibited LPS-induced apoptosis signaling pathway activation. Our results suggested that berberine could inhibit LPS-induced apoptosis and the production of proinflammatory mediators in HGFs cells. Berberine may be a potential therapeutic drug for the management of periodontitis.

Investigation of the synergistic effect of melt-extension and nanofiller on the crystal-crystal phase transition from form II to I of isotactic polybutene-1.

New questions and conjectures are raised on the crystal-crystal phase transition of isotactic polybutene-1 (iPB-1) containing nanofiller in the flow field. In this work, we investigate the phase transition from flow-induced oriented form II to I in iPB-1 blends with multi-walled carbon nanotubes (MWCNTs) with a homemade two-drum extensional rheometer combined with in situ wide-angle X-ray diffraction (WAXD) measurements. The MWCNTs show a limited promoting effect on the phase transition kinetics under quiescent conditions, while the phase transition kinetic is highly accelerated with the impose of melt-extension. When the loading extension strain is 0.5 or 2.0, the half time of phase transition (t1/2) is shortened from tens of hours to a few hours, depending on the melt-extension strain and the MWCNTs content in iPB-1. When the extension strain increases to 3.5, t1/2 decreases to about 30 min, which is independent of the MWCNTs content in all iPB-1 blends except in blends with MWCNTs content of 1%, where the phase transition rate in the middle and late stages is restrained. It's speculated that flow-induced molecular orientation or shish-kebab morphology affects the internal stress or stress transfer. The addition of a nanofiller enlarged the effect of melt-extension through strengthening the localized intensity of flow field. In general, the combination of nanofiller and melt-extension can obviously promote the phase transition kinetics.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

PAP Polypeptide Promotes Osteogenesis in Jaw Bone Defect Repair by Inhibiting Inflammatory Reactions.

Jaw defects are common in oral and maxillofacial diseases and require surgical repair in extreme cases. Given the limitations in availability and efficacy of autologous bone grafts or allografts, great effort has been made in finding suitable, biocompatible, and effective artificial bone materials. Considering the key role of inflammation in bone resorption, we sought to identify a polypeptide with anti-inflammatory and bone-promoting effects. Rat bone marrow-derived mesenchymal cells (BMSCs) were treated with lipopolysaccharide (LPS) to induce an inflammatory environment, and 1,538 differentially abundant polypeptides were identified using mass spectrometry. Based on mass spectrometry signal intensity, multiple of difference, and structural stability, PAP was screened out as the polypeptide with the lowest abundance in the inflammatory condition. PAP showed no cytotoxicity to BMSCs with increasing concentrations. PAP (10 µM) also increased alkaline phosphatase activity and mRNA expression of Ocn, Bmp2, and Runx2 in a concentration-dependent manner, which confirmed that it can promote osteogenic induction of rat BMSCs. Moreover, PAP reduced LPS-induced expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and reactive oxygen species and inhibited polarization of RAW 264.7 macrophages to the inflammatory type. Finally, a skull defect mouse model was established, and mice were injected with LPS and/or PAP. Micro-CT, histological analysis, and immunohistochemical staining showed that PAP significantly reduced the number of LPS-induced bone resorption pits and maintained bone integrity. Overall, the polypeptide PAP screened using LPS stimulation of BMSCs is not cytotoxic and can inhibit the inflammatory reaction process to promote osteogenesis. This study thus provides a basis for development of PAP as a new osteogenic material in the repair of jaw defects.

Small Area Variation of Adherence to Clinical Recommendations: An Example from Switzerland.

Background: Unwarranted variation in healthcare utilization can only partly be explained by variation in the health care needs of the population, yet it is frequently found globally. This is the first cross-sectional study that systematically assessed geographic variation in the adherence to clinical recommendations in Switzerland. Specifically, we explored 1) the geographic variation of adherence to clinical recommendations across 24 health services at the sub-cantonal level, 2) assessed and mapped statistically significant spatial clusters, and 3) explored possible influencing factors for the observed geographic variation. Methods: Exploratory spatial analysis using the Moran's I statistic on multivariable multilevel model residuals to systematically identify small area variation of adherence to clinical recommendations across 24 health services. Results: Although there was no overall spatial pattern in adherence to clinical recommendations across all health care services, we identified health services that exhibited statistically significant spatial dependence in adherence. For these, we provided evidence about the locations of local clusters. Interpretation: We identified regions in Switzerland in which specific recommended or discouraged health care services are utilized less or more than elsewhere. Future studies are needed to investigate the place-based social determinants of health responsible for the sub-cantonal variation in adherence to clinical recommendations in Switzerland and elsewhere over time.

Polymeric coating on ß-TCP scaffolds provides immobilization of small extracellular vesicles with surface-functionalization and ZEB1-Loading for bone defect repair in diabetes mellitus.

Repair of critical-size bone defects in patients with diabetes mellitus (DM) has always been a challenge in clinical treatment. The process of bone defect regeneration can be impaired by underlying diseases including DM, but the mechanism remains unclear. In bone tissue engineering, the integration of bionic coatings and bioactive components into basic scaffolds are common function-enhancing strategies. Small extracellular vesicles (sEVs) have been applied for cell-free tissue regeneration in the last few years. We previously reported that sEVs have flexible and easily-extensible potential, through modular design and engineering modification. The impairment of CD31hiendomucinhi endothelial cells (ECs) whose function is coupling of osteogenesis and angiogenesis, is considered an important contributor to diabetic bone osteopathy, and ZEB1, which is highly expressed in CD31hiendomucinhi ECs, promotes angiogenesis-dependent bone formation. Thus we believe these ECs hold much promise for use in bone regeneration. In addition, c(RGDfC) has been reported to be a highly-effective peptide targeting αvß3, which is highly expressed in the bone microenvironment. In this study, we developed a hyaluronic acid (HA)/poly-L-lysine (PLL) layer-by-layer (LbL) self-assembly coating on ß-TCP (ß-tricalcium phosphate) scaffolds providing immobilization of modularized engineered sEVs (with c(RGDfC) surface functionalization and ZEB1 loading) to facilitate bone defect regeneration under DM conditions. RNA-seq was used to explore possible molecular mechanisms, and the therapeutic effects of bone regeneration were systematically evaluated in vitro and in vivo. Our data demonstrated that this strategy could be very effective in promoting the repair of diabetic bone defects, by enhancing angiogenesis, promoting osteogenesis and inhibiting osteoclast formation.

Surgical procedures in inpatient versus outpatient settings and its potential impact on follow-up costs.

OBJECTIVE: We examined real-world effects of cantonal legislations to direct surgery patients from the inpatient to the outpatient setting in Switzerland. METHODS: Analyses were based on claims data of the Helsana Group, a leading Swiss health insurance. The study population consisted of 13'145 (in 2014), 12'455 (in 2016), and 12'875 (in 2018) insured persons aged >18 years who had haemorrhoidectomy, inguinal hernia repair, varicose vein surgery, knee arthroscopy/meniscectomy or surgery of the cervix/uterus. We assessed the proportion of inpatient procedures, index costs, length of hospital stays, outpatient costs and hospitalizations during follow-up, stratified by procedure, in-/outpatient setting, and the presence (enacted/effective in 2018) of a cantonal legislation. We used difference-in-differences methods to study the impact of cantonal legislations. RESULTS: Overall, the proportion of procedures performed in the inpatient setting decreased between 2014 and 2018 (p < 0.001). The decrease between 2016 and 2018 was significantly steeper in cantons with a legislation (p < 0.001; effect size: 0.57; 95% CI: 0.51, 0.64), leading to steeper decreases in healthcare costs of index procedures in cantons with a legislation, with no impact on length of hospital stays. The legislation also had no impact on outpatient costs or hospitalizations during follow-up. CONCLUSIONS: The cantonal legislations achieved the intended effects of inpatient surgery substitution by outpatient surgery, with no evidence suggesting negative effects on costs or hospitalizations during follow-up.

Are weak or negative clinical recommendations associated with higher geographical variation in utilisation than strong or positive recommendations? Cross-sectional study of 24 healthcare services.

OBJECTIVES: When research evidence is lacking, patient and provider preferences, expected to vary geographically, might have a stronger role in clinical decisions. We investigated whether the strength or the direction of recommendation is associated with the degree of geographic variation in utilisation. DESIGN: In this cross-sectional study, we selected 24 services following a comprehensive approach. The strength and direction of recommendations were assessed in duplicate. Multilevel models were used to adjust for demographic and clinical characteristics and estimate unwarranted variation. SETTING: Observational study of claims to mandatory health insurance in Switzerland in 2014. PARTICIPANTS: Enrolees eligible for the 24 healthcare services. PRIMARY OUTCOME MEASURES: The variances of regional random effects, also expressed as median odds ratios (MOR). Services grouped by strength and direction of recommendations were compared with Welch's t-test. RESULTS: The sizes of the eligible populations ranged from 1992 to 409 960 patients. MOR ranged between 1.13 for aspirin in secondary prevention of myocardial infarction to 1.68 for minor surgical procedures performed in inpatient instead of outpatient settings. Services with weak recommendations had a negligibly higher variance and MOR (difference in means (95% CI) 0.03 (-0.06 to 0.11) and 0.05 (-0.11 to 0.21), respectively) compared with strong recommendations. Services with negative recommendations had a slightly higher variance and MOR (difference in means (95% CI) 0.07 (-0.03 to 0.18) and 0.14 (-0.06 to 0.34), respectively) compared with positive recommendations. CONCLUSIONS: In this exploratory study, the geographical variation in the utilisation of services associated with strong vs weak and negative vs positive recommendations was not substantially different, although the difference was somewhat larger for negative vs positive recommendations. The relationships between the strength or direction of recommendations and the variation may be indirect or modified by other characteristics of services. As initiatives discouraging low-value care are gaining attention worldwide, these findings may inform future research in this area.

Geospatial Analysis of COVID-19: A Scoping Review.

The outbreak of SARS-CoV-2 in Wuhan, China in late December 2019 became the harbinger of the COVID-19 pandemic. During the pandemic, geospatial techniques, such as modeling and mapping, have helped in disease pattern detection. Here we provide a synthesis of the techniques and associated findings in relation to COVID-19 and its geographic, environmental, and socio-demographic characteristics, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology for scoping reviews. We searched PubMed for relevant articles and discussed the results separately for three categories: disease mapping, exposure mapping, and spatial epidemiological modeling. The majority of studies were ecological in nature and primarily carried out in China, Brazil, and the USA. The most common spatial methods used were clustering, hotspot analysis, space-time scan statistic, and regression modeling. Researchers used a wide range of spatial and statistical software to apply spatial analysis for the purpose of disease mapping, exposure mapping, and epidemiological modeling. Factors limiting the use of these spatial techniques were the unavailability and bias of COVID-19 data-along with scarcity of fine-scaled demographic, environmental, and socio-economic data-which restrained most of the researchers from exploring causal relationships of potential influencing factors of COVID-19. Our review identified geospatial analysis in COVID-19 research and highlighted current trends and research gaps. Since most of the studies found centered on Asia and the Americas, there is a need for more comparable spatial studies using geographically fine-scaled data in other areas of the world.

Temporal trends and regional disparities in cancer screening utilization: an observational Swiss claims-based study.

BACKGROUND: We examined colorectal, breast, and prostate cancer screening utilization in eligible populations within three data cross-sections, and identified factors potentially modifying cancer screening utilization in Swiss adults. METHODS: The study is based on health insurance claims data of the Helsana Group. The Helsana Group is one of the largest health insurers in Switzerland, insuring approximately 15% of the entire Swiss population across all regions and age groups. We assessed proportions of the eligible populations receiving colonoscopy/fecal occult blood testing (FOBT), mammography, or prostate-specific antigen (PSA) testing in the years 2014, 2016, and 2018, and calculated average marginal effects of individual, temporal, regional, insurance-, supply-, and system-related variables on testing utilization using logistic regression. RESULTS: Overall, 8.3% of the eligible population received colonoscopy/FOBT in 2014, 8.9% in 2016, and 9.2% in 2018. In these years, 20.9, 21.2, and 20.4% of the eligible female population received mammography, and 30.5, 31.1, and 31.8% of the eligible male population had PSA testing. Adjusted testing utilization varied little between 2014 and 2018; there was an increasing trend of 0.8% (0.6-1.0%) for colonoscopy/FOBT and of 0.5% (0.2-0.8%) for PSA testing, while mammography use decreased by 1.5% (1.2-1.7%). Generally, testing utilization was higher in French-speaking and Italian-speaking compared to German-speaking region for all screening types. Cantonal programs for breast cancer screening were associated with an increase of 7.1% in mammography utilization. In contrast, a high density of relevant specialist physicians showed null or even negative associations with screening utilization. CONCLUSIONS: Variation in cancer screening utilization was modest over time, but considerable between regions. Regional variation was highest for mammography use where recommendations are debated most controversially, and the implementation of programs differed the most.

Going beyond the mean: economic benefits of myocardial infarction secondary prevention.

BACKGROUND: Using the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account. METHODS: Swiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12 inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis. RESULTS: Only 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (- 4865 Swiss Francs [95% confidence interval - 8027; - 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median. CONCLUSIONS: Compliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone.

Degree of regional variation and effects of health insurance-related factors on the utilization of 24 diverse healthcare services - a cross-sectional study.

BACKGROUND: Regional variation in healthcare utilization could reflect unequal access to care, which may lead to detrimental consequences to quality of care and costs. The aims of this study were to a) describe the degree of regional variation in utilization of 24 diverse healthcare services in eligible populations in Switzerland, and b) identify potential drivers, especially health insurance-related factors, and explore the consistency of their effects across the services. METHODS: We conducted a cross-sectional study using health insurance claims data for the year of 2014. The studied 24 healthcare services were predominantly outpatient services, ranging from screening to secondary prevention. For each service, a target population was identified based on applicable clinical recommendations, and outcome variable was the use of the service. Possible influencing factors included patients' socio-demographics, health insurance-related and clinical characteristics. For each service, we performed a comprehensive methodological approach including small area variation analysis, spatial autocorrelation analysis, and multilevel multivariable modelling using 106 mobilité spaciale regions as the higher level. We further calculated the median odds ratio in model residuals to assess the unexplained regional variation. RESULTS: Unadjusted utilization rates varied considerably across the 24 healthcare services, ranging from 3.5% (osteoporosis screening) to 76.1% (recommended thyroid disease screening sequence). The effects of health insurance-related characteristics were mostly consistent. A higher annual deductible level was mostly associated with lower utilization. Supplementary insurance, supplementary hospital insurance and having chosen a managed care model were associated with higher utilization of most services. Managed care models showed a tendency towards more recommended care. After adjusting for multiple influencing factors, the unexplained regional variation was generally small across the 24 services, with all MORs below 1.5. CONCLUSIONS: The observed utilization rates seemed suboptimal for many of the selected services. For all of them, the unexplained regional variation was relatively small. Our findings confirmed the importance and consistency of effects of health insurance-related factors, indicating that healthcare utilization might be further optimized through adjustment of insurance scheme designs. Our comprehensive approach aids in the identification of regional variation and influencing factors of healthcare services use in Switzerland as well as comparable settings worldwide.