'Value-based methodology for person-centred, integrated care supported by Information and Communication Technologies' (ValueCare) for older people in Europe: study protocol for a pre-post controlled trial.

BACKGROUND: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023. METHODS: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data. DISCUSSION: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings. TRIAL REGISTRATION: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021.

"Comparative study of conventional anesthesia technique versus computerized system anesthesia: a randomized clinical trial".

OBJECTIVE: The aim of the present study was to compare in terms of pain perception the use of conventional anesthesia and a computerized system. MATERIALS AND METHODS: Forty patients in need for extractions, dental restorative, or periodontal treatment bilaterally, were selected. Each patient served as his/her own control being subjected to two anesthesia techniques: conventional and electronically controlled anesthesia with Calaject® (Rønvig Dental MFG, Daugaard, Denmark). Each patient received both treatments in a blind way 1 week apart. The order was previously randomized. After performing the anesthesia (upper dental nerve, palatal posterior nerve, or inferior alveolar nerve), the patients evaluated their pain sensation with a visual analogue scale (VAS) (0-10). After treatment, the patients were asked about the presence of pain during the procedure. Finally, the patients selected their preference between the conventional and electronic anesthesia technique. Differences in assessment of pain's injection were analyzed using the Wilcoxon test and the Kruskal-Wallis test (α = 0.05). RESULTS: The mean general pain experienced was 3.73 (1.55 SD) for the conventional anesthesia, and 1.95 (0.53 SD) for computerized anesthesia. Statistical differences (p < 0.05) were found. There was no difference between the treatments (p value = 0.061). Most patients did not feel any pain during the treatment. Finally, 92.5% of the patients preferred the electronic system. CONCLUSIONS: Computerized anesthesia system produces significantly less pain compared with a conventional anesthesia syringe. Although both obtained sufficient anesthetic depth to perform treatments, the majority of patients chose electronic anesthesia as the most satisfactory. CLINICAL RELEVANCE: Computerized anesthesia devices are valid and more comfortable alternative to conventional anesthesia.

Influence of conventional and digital intraoral impressions on the fit of CAD/CAM-fabricated all-ceramic crowns.

OBJECTIVES: To compare the fit of all-ceramic crowns fabricated from conventional silicone impressions with the fit of all-ceramic crowns fabricated from intraoral digital impressions. METHODS: Thirty patients with 30 posterior teeth with a prosthetic demand were selected. Zirconia-based ceramic crowns were made using an intraoral digital impression system (Ultrafast Optical Sectioning technology) (digital group, D) and 2-step silicone impression technique (conventional group, C). To replicate the interface between the crown and the preparation, each crown was cemented on its corresponding clinical preparation using ultra-flow silicone. Each crown was embedded in resin to stabilize the registered interface. Specimens were sectioned in buccolingual orientation, and internal misfit was measured at different areas using stereomicroscopy (×40). Data was analysed using Student's t test and Mann-Whitney test (α = 0.05). RESULTS: No statistically significant differences were found (P > 0.05) between two groups. The mean internal misfit and mean marginal misfit were 170.9 µm (SD = 119.4)/106.6 µm (SD = 69.6) for group D and 185.4 µm (SD = 112.1)/119.9 µm (SD = 59.9) for group C. CONCLUSION: Ceramic crowns fabricated using an intraoral scanner are comparable to elastomer conventional impressions in terms of their marginal and internal fits. The mean marginal fit in both groups was within the limits of clinical acceptability. CLINICAL SIGNIFICANCE: Impressions based on Ultrafast Optical Sectioning technology can be used for manufacturing ceramic crowns in a normal workflow, with the same results as silicone conventional impressions.

Combined analysis of copy number alterations by single-nucleotide polymorphism array and MYC status in non-metastatic breast cancer patients: comparison according to the circulating tumor cell status.

Recent technological advances have made it possible to detect circulating tumor cells (CTCs) as a prognostic marker in operable breast cancer patients. Whether the presence of CTCs in cancer patients correlates with molecular alterations in the primary tumor has not been widely explored. We identified 14 primary breast cancer specimens with known CTC status, in order to evaluate the presence of differential genetic aberrations by using SNP array assay. There was a global increase of altered genome, CNA, and copy-neutral loss of heterozygosity (cn-LOH) observed in the CTC-positive (CTC(+)) versus CTC-negative (CTC(-)) cases. As the preliminary results showed a higher proportion of copy number alteration (CNA) at 8q24 (MYC loci) and the available evidence supporting the role of MYC in the processes cancer metastases is conflicting, MYC status was determined in tissue microarray sections in a larger series of patients (n = 49) with known CTC status using FISH. MYC was altered in 62% (16/26) CTC(+) patients and in 43% (6/14) CTC(-) patients (p = 0.25). Based on the observation in our study, future studies involving a larger number of patients should be performed in order to definitively define if this correlation exists.

Clinical evaluation of posterior zirconia-based and porcelain-fused-to-metal crowns with a vertical preparation technique: an up to 5-year retrospective cohort study.

OBJECTIVE: To evaluate the clinical conditions of single-unit posterior restorations on teeth prepared without finishing line, after 5.6 years of clinical service. MATERIALS AND METHODS: 50 crowns (25 zirconia-based (Zr) and 25 porcelain-fused-to-metal (PFM)) were selected from 34 patients. The restorations were evaluated according to the California Dental Association (CDA) Quality Criteria, and periodontal variables were studied in the abutment teeth compared with the unrestored contralateral teeth. Variables were examined using Mann-Whitney and Pearson´s Chi-Square tests (α = 0.05). The success of the prosthesis was calculated using Kaplan-Meier test. RESULTS: CDA Quality Criteria was considered satisfactory-excellent in all restorations except for one of them, due to chipping on a PFM crown. At, 66 months, the success rates for PFM and Zr crowns were 85.7 % and 100 %, respectively. The plaque index (PI) showed that the restored abutment teeth accumulated significantly less plaque than the control teeth, but the gingival index (GI) was statistically higher in the abutment teeth. In 80 % of cases the probing depth (PB) was ≤3 mm. In addition, in 21 % of the cases, gingival recession was less than 2 mm. The restoration material had a statistically significant effect on GI and PB, with Zr crowns showing less inflammation and less deep pockets than PFM restorations. On the contrary, greater gingival recession was found at the margins of the Zr crowns when compared to the PFM. No statistical differences were found between the two materials in the GI. CONCLUSIONS: Cemented crowns on vertical preparations show good clinical behavior after 5 years. The periodontal parameters (PI, GI, PD) of the Zr restorations are significantly better than those of PFM, with the exception of gingival recession. CLINICAL RELEVANCE: The use of restorations on vertically prepared teeth is a suitable alternative to classical horizontal preparations.

Thalidomide in the treatment of refractory cutaneous lupus erythematosus: prognostic factors of clinical outcome.

BACKGROUND: Although thalidomide has been shown to be effective in patients with refractory cutaneous lupus erythematosus (CLE), its use is still hampered by its potential severe side-effects and the current restricted availability. OBJECTIVES: To evaluate prospectively the clinical efficacy and safety of low-dose thalidomide in an observational study and to establish prognostic factors of clinical outcome. METHODS: Sixty consecutive patients with refractory CLE were treated with thalidomide (100 mg daily). Clinical response was assessed by the CLE Disease Area and Severity Index (CLASI). Clinical and immunological parameters were evaluated during treatment. RESULTS: Patients were followed for up to 8 years (range 2-18). One patient discontinued treatment because of side-effects. Of the 59 remaining patients, 58 (98%) achieved clinical response, already noticeable at 2 weeks following treatment. Complete response occurred in 50 patients (85%). Clinical relapse was frequent (70%) and usually occurred 5 months after withdrawal or reduction of thalidomide. Subacute CLE (SCLE) was the predicting factor of long-term remission after therapy discontinuation [odds ratio (OR) 30, 95% confidence interval (CI) 5·82-154·63], whereas discoid lupus erythematosus (DLE) was predictive of relapse (OR 5·71, 95% CI 1·36-24·06). Eleven patients (18%) reported paraesthesia; in five of the 11, nerve conduction studies confirmed a sensory polyneuropathy. Neurological symptoms resolved in 12 months (range 6-18) after thalidomide withdrawal. Two patients, heavy smokers and without antiphospholipid antibodies, had a cerebral ischaemic event. CONCLUSIONS: Low-dose thalidomide is an effective treatment for refractory CLE, but its benefits need to be balanced against the potential adverse effects. Whereas DLE forms tended to relapse and required a long-term maintenance dose of thalidomide, SCLE forms showed a sustained remission after withdrawal.

MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.

BACKGROUND: Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target. METHODS: To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed. RESULTS: In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a multivariate analysis. CONCLUSIONS: MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease.

A comprehensive genetic and histopathologic analysis identifies two subgroups of B-cell malignancies carrying a t(14;19)(q32;q13) or variant BCL3-translocation.

The biologic and pathologic features of B-cell malignancies bearing a translocation t(14;19)(q32;q13) leading to a fusion of IGH and BCL3 are still poorly described. Herein we report the results of a comprehensive cytogenetic, fluorescence in situ hybridization (FISH), molecular and histopathological survey of a large series of B-cell malignancies with t(14;19) or variant translocations. A total of 56 B-cell malignancies with a FISH-proven BCL3 involvement were identified with the translocation partners being IGH (n=51), IGL (n=2), IGK (n=2) and a non-IG locus (n=1). Hierarchical clustering of chromosomal changes associated with the t(14;19) indicated the presence of two different groups of IG/BCL3-positive lymphatic neoplasias. The first group included 26 B-cell malignancies of various histologic subtypes containing a relatively high number of chromosomal changes and mostly mutated IgVH genes. This cluster displayed three cytogenetic branches, one with rearrangements in 7q, another with deletions in 17p and a third one with rearrangements in 1q and deletions in 6q and 13q. The second group included 19 cases, mostly diagnosed as B-cell chronic lymphocytic leukemia (B-CLL), and characterized by few additional chromosomal changes (e.g. trisomy 12) and unmutated IgVH genes. In conclusion, our study indicates that BCL3 translocations are not restricted to B-CLL but present in a heterogeneous group of B-cell malignancies.

Duplication dup(1)(q41q44) defined by fluorescence in situ hybridization: delineation of the 'trisomy 1q42-->qter syndrome'.

We report on a novel case of pure partial tandem duplication 1q42q43 confirmed by fluorescence in situ hybridization (FISH). We compare the manifestations of our patient with similar cases previously reported. We conclude that the most common clinical manifestations of trisomy 1q42qter are prenatal and postnatal growth retardation, relative macrocephaly, triangular face, prominent forehead, broad nasal bridge, abnormal philtrum, micro/retrognathia, cardiac defects and mental retardation. We would like to emphasize the importance of the FISH technique in the identification of the duplicated segment.

Paraneoplastic pemphigus associated with Castleman's disease: usefulness of the laboratory of autoimmunity in the diagnosis of this disease.

We report on a case of paraneoplastic pemphigus associated with Castleman's disease. Clinical pathologic features were not conclusive. Diagnosis was established thanks to the detection of seric autoantibodies directed against intercellular substance by indirect immunofluorescence on monkey esophagus. The positive result of this test prompted us to reevaluate the patient and to detect the occult neoplasia. The demonstration of autoantibodies against plakins is the key marker of this disease but depends on tests that may not be readily available in many places like immunoprecipitation, immunoblotting, or indirect immunofluorescence over rat bladder. In this setting, tests like indirect immunofluorescence over monkey esophagus, although unspecific, may aid in reaching the appropriate diagnosis. This case illustrates the importance of the laboratory of autoimmunity in the diagnosis of this type of pemphigus.

Primitive neuroectodermal tumor of the central nervous system with glial differentiation: a FISH study of an adult case.

Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS), a rare occurrence in adults, may show glial differentiation and can be misinterpreted as pure astrocytic neoplasms. Few fluorescence in situ hybridization (FISH) studies have been carried out on these tumors; isochromosome 17q was found to be the major chromosomal abnormality. We present the case of an adult in which we performed a FISH study of both the glial and neuronal components. A complex array of FISH changes, not including an isochromosome 17q were identified.

Neuropeptides bombesin and calcitonin induce resistance to etoposide induced apoptosis in prostate cancer cell lines.

BACKGROUND: Neuroendocrine differentiation in prostatic carcinoma has been related to regulation of proliferation and metastatic potential and correlated with prognosis. More than 80% of prostate carcinomas initially respond to androgen ablation, but most relapse, due to the heterogeneous presence of androgen-dependent and independent clones. The pathways of cellular proliferation and apoptosis are inexorably linked to minimize the occurrence of neoplasia, and disfunction of apoptosis is proposed as a pathogenic process in malignant tumors. Androgen-dependent prostatic cancer cells undergo apoptosis after androgen deprivation, but not androgen-independent ones due to a defect in the initiation step. Anyway, they retain the basic cellular machinery to undergo apoptosis. We suggest a possible role of neuroendocrine differentiation in the onset and regulation of apoptosis in prostatic neoplasia. METHODS: LNCaP, PC-3 and DU 145 prostatic cancer cell lines were induced to undergo apoptosis after treatment with etoposide alone or plus androgen ablation. We tested the role of neuropeptides bombesin and calcitonin at modulating etoposide induced apoptosis. RESULTS: Etoposide-induced apoptosis in all cancer cell lines was achieved. In LNCaP androgen ablation was also required. Apoptosis is prevented in all three lines when bombesin was added. Calcitonin addition prevents apoptosis in PC-3, LNCaP and in an etoposide dose-dependent way in DU 145. CONCLUSION: Neuropeptides bombesin and calcitonin can modulate the apoptotic response of prostate cancer cells by inducing resistance to etoposide-induced apoptosis, suggesting that neuropeptides can be used as a target of therapeutical approach in prostatic carcinoma.

Neuropeptides, apoptosis and ion changes in prostate cancer. Methods of study and recent developments.

It has been suggested that neuroendocrine (NE) cells provide paracrine stimuli for the propagation of local carcinoma cells and that NE differentiation is associated with the progression of prostate cancer toward an androgen-independent state. Apoptosis comprises a critical intracellular defense mechanism against tumorigenic growth and is associated with a number of changes in the elemental content of the cell. The neuropeptides bombesin and calcitonin, which inhibit etoposide-induced apoptosis, also inhibit the etoposide-induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This protective effect on etoposide-induced apoptosis appears to be quite similar in androgen-dependent and androgen-independent cell lines. This confirms that neuropeptides confer antiapoptotic capabilities on non-neuroendocrine cells in close proximity to neuroendocrine cells. It can therefore be speculated that certain neuroendocrine peptides can increase the survival and further growth of neighboring cells and may thereby contribute to the aggressive clinical course of prostate tumors containing neuroendocrine elements. In addition, this correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma. The culture techniques described were, thus, designed in order to achieve two important goals. First, the development of an in vitro model that allows an approach to neuroendocrine differentiation in prostate cancer and its role in apoptosis blockage. Second, the method has been designed in order to permit rapid cryofixation of intact cell monolayers for subsequent x-ray microanalysis.

Etoposide sensitivity of human prostatic cancer cell lines PC-3, DU 145 and LNCaP.

Metastatic prostatic cancer is typically refractory to androgen ablation therapy due to the presence of androgen-independent clones in the neoplasia. A therapeutical approach which could effectively control androgen-dependent and independent cells is, thus, needed. Maybe the failure of certain cancer cells to engage in apoptosis could explain the inherent drug resistance of many tumors. Anyway, these cells can retain the ability to undergo apoptosis in response to an adequate stimulus. We tested whether etoposide, a topoisomerase II inhibitor, could induce apoptosis in androgen-dependent (LNCaP) as well as independent (PC-3 and DU 145) human prostate cancer cell lines. Morphological examination was performed, as it is regarded as one of the most reliable parameters for the detection of apoptotic changes. Complementarily, biochemical and flow cytometric studies were also used. Characteristical changes of apoptosis were demonstrated in PC-3, Du 145, and LNCaP cancer cells after treatment with etoposide. These cells, thus, retain the ability to undergo apoptosis under adequate conditions, in a promising approach to hormone refractory prostate cancer therapy.

New t(11;12)(q12;q11) characterized by RxFISH in a patient with T-cell large granular lymphocyte leukemia.

Chromosomal abnormalities in patients with large granular lymphocyte leukemia (LGLL) are rare. Herein we present a novel cytogenetic abnormality t(11;12)(q12;q11) in a patient with LGLL identified by cross-species color banding (RxFISH). The application of RxFISH allowed the rapid and easy identification of a chromosome rearrangement that was not recognized by conventional cytogenetics. Therefore, RxFISH is a suitable complement to, but not a replacement for, conventional cytogenetics.

In-vitro effect of pirenzepine on motility of canine gall-bladder.

The action of pirenzepine as an antimuscarinic drug has been investigated on motor responses of muscle strips in the canine gall-bladder. Pirenzepine was further used to examine whether gall-bladder motor responses to synthetic sulphated cholecystokinin octapeptide (CCK-8) are sensitive to pirenzepine. Pirenzepine (10(-9)-10(-5) M) antagonized muscle contractions in response to acetylcholine (10(-9)-10(-2) M) and CCK-8 (10(-11)-10(-6) M) in a significant manner. These findings indicate that pirenzepine is a potent antagonist of two substances that are the principal contractile mediators of gall-bladder contraction and suggest that long-term administration of pirenzepine could contribute to stasis of the gall-bladder.

[The epidemiology of central venous catheterization (CVC) in parenteral nutrition. The clinical implications and factors that determine the selection of germs]. / Epidemiología de la cateterización venosa central (CVC) en nutrición parenteral. Implicaciones clínicas y factores que determinan la selección de gérmenes.

The objective of the study is, on one hand, to determine the etiology and the clinical implications as a function of the isolated germ, of central venous catheterization in patients with parenteral nutrition in our hospital, and on the other hand, to determine which factors are associated with the selection of germs of central venous catheterization in parenteral nutrition. For this we included venous catheters, colonized for 5 years, and with a study of the different segments (connection, insertion point, and tip). As a function of the appearance of associated clinical symptoms, of the results of the blood culture, and of the clinical evolution of the patient, the variables which determine the level of pathogenicity of the different groups of germs in the central venous catheterization, are defined; for the study of the factors associated with the selection of the different groups of germs, 8 variables were chosen. The data obtained are statistically treated, and the results are considered to be significant if p < 0.05. The understanding of the different factors associated with the selection of germs, and the level of clinical pathogenesis of the different groups, allows a better level of the clinical action in the prevention of the infection associated with the catheter.