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1.
Background and aims: Sharing of unsterile injection equipment among people who inject drugs (PWID) is the major transmission-route for hepatitis C (HCV). HCV is highly prevalent in PWID in the Stockholm needle exchange programme (NEP). The frequency of advanced liver fibrosis among the participants is, however, unknown.

Methods: From December 2016 to April 2018, all participants with chronic hepatitis C infection (CHC) were offered liver fibrosis evaluation at the Stockholm NEP, including liver stiffness measurement (LSM), a medical history and expanded blood tests to evaluate APRI and FIB-4 scores.

Results: A total of 2037 individuals were enrolled of whom 964 (47.3%) had CHC. LSM was performed in 203 (21.1%) of eligible participants of whom 85% had mild fibrosis (LSM ≤9.4?kPa) and 15% advanced fibrosis (LSM ≥9.5?kPa). APRI >1 and FIB-4?>?3.25 only identified 30% of participants with advanced fibrosis. However, all 31(100%) participants with advanced fibrosis were detected when APRI >1 was combined with an age of ≥40 years and an injection drug use (IDU) duration of ≥15 years.

Conclusions: We found that the diagnostic work-up for advanced fibrosis can be simplified with this combination of easily available factors. This allows identification of PWID in need of immediate HCV treatment to prevent further disease progression. Furthermore, LSM can be avoided among PWID with mild fibrosis, identified by age <40 years combined with IDU duration of <15 years and APRI score <1. This strategy enhances the HCV care cascade where LSM is not easily available, and will thus facilitate HCV treatment initiation.  相似文献   


2.
Objective: To assess the transthyretin (TTR) stabilization activity of tolcapone (SOM0226) in patients with hereditary ATTR amyloidosis, asymptomatic carriers and healthy volunteers.

Methods: A phase IIa proof-of-concept trial included two phases separated by a 6-week washout period. Phase A: single 200?mg dose of tolcapone; phase B: three 100?mg doses taken at 4?h intervals. The primary efficacy variable was TTR stabilization.

Results: Seventeen subjects were included (wild type, n?=?6; mutation TTR Val30Met, n?=?11). TTR stabilization was observed in all participants. Two hours after dosing, 82% of participants in phase A and 93% of those in phase B reached a TTR stabilization value of at least 20%. In phase A, there was an increase of 52% in TTR stabilization vs baseline values 2?h after dosing, which decreased to 22.9% at 8?h. In phase B, there was a significant increase of 38.8% in TTR stabilization 2?h after the first 100?mg dose. This difference was maintained after 10?h and decreased after 24?h. No serious adverse events were observed.

Conclusions: The ability of tolcapone for stabilizing TTR supports further development and repositioning of the drug for the treatment of ATTR amyloidosis.

EudraCT trial number: 2014-001586-27

ClinicalTrials.gov Identifier: NCT02191826  相似文献   


3.
Objectives: Conceiving narration as a resource to promote older people’s wellbeing, the present work aimed to implement a narrative-based intervention to empower the subjective and psychological wellbeing of older adults living in nursing homes.

Methods: Twenty-one nursing-home residents took part in a narrative training experience consisting of three weekly interview sessions. During each interview, a psychologist helped the participants to construct an autobiographical narrative about their present life in the nursing home based on a Deconstruction-Reconstruction technique. Subjective and psychological wellbeing variables were assessed before and after the intervention.

Results: Subjective but not psychological wellbeing increased over the course of the intervention. The participants reported to appreciate the intervention.

Conclusions: Although preliminary, the results suggest that brief narrative training based on narrative therapy can positively affect nursing-home residents’ subjective wellbeing.

Clinical Implications: Brief narrative interventions implementing deconstruction-reconstruction techniques are feasible for long-term care residents.  相似文献   


4.
Age-related reference intervals (RIs) of aortic pulse wave velocity (Ao-PWV) obtained from a large healthy population are lacking in South America. The aims of this study were to determine Ao-PWV RIs in a cohort of healthy children and adolescents from Argentina and to generate year-to-year percentile curves.

Ao-PWV was measured in 1000 healthy subjects non-exposed to traditional cardiovascular risk factors (Age: 10–22 y. o., 56% males). First, we evaluated if RIs for males and females were necessaries (correlation and covariate analysis). Second, mean (M) and standard deviation (SD) age-related equations were obtained for cf-PWV, using parametric regression methods based on fractional polynomials. Third, age-specific (year to year) percentiles curves (for all, males and females children and adolescents) were generated using the standard normal distribution. They were, age-specific 1st, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th and 99th percentile curves and values.

After covariate analysis (i.e., adjusting by age, jugulum-symphysis distance, body weight and height), specific RIs for males and females of children and adolescents were evidenced as necessaries. The equations were

For all subjects:

Ao-PWV_Mean = 4.98 + 12.86x10?5 Age3.

Ao-PWV_SD = 0.47 + 21.00x10?6Age3.

For girls:

Ao-PWV_Mean = 5.07 + 10.23x10?5Age3.

Ao-PWV_SD = 0.50 + 10.00x10?6Age3.

For boys:

Ao-PWV_Mean = 4.87 + 15.81x10?5Age3.

Ao-PWV_SD = 0.46 + 22.34x10?6Age3.

Our study provides the largest database to-date concerning Ao-PWV in healthy children and adolescents in Argentina. Age-related equations (M and SD values) for Ao-PWV are reported by the first time. Specific RIs and percentiles of Ao-PWV are now available according to age and sex for an Argentinian population.  相似文献   


5.
6.
Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy.

Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety.

Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted.

Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn’s disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported.

Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.  相似文献   


7.
Objectives: To evaluate the cognitive, neuropsychiatric, and quality of life outcomes of computer-based cognitive training and social interaction on people with mild to moderate dementia.

Methods: Ten individuals with dementia were recruited to complete a cognitive training regimen. They were randomly assigned to a high social interaction (HSI) group (n = 5) and low social interaction (LSI) group (n = 5). Eight of the original 10 participants completed the cognitive training and were evaluated on cognitive abilities, neuropsychiatric symptoms (NPS), and quality of life (QoL).

Results: Mean scores for the HSI group increased on cognitive assessments, where mean scores for the LSI group saw decline, or stability. There was an overall reduction in the frequency and severity of NPS presentation in both the HSI and LSI group. Mixed results were found for mean changes in QoL.

Discussion: These results support the idea of social interaction influencing cognitive outcomes, cognitive training influencing NPS, and both social interaction and cognitive training influencing QoL. The findings illustrate the feasibility and importance of incorporating social activity to computerized cognitive training for people with dementia.

Clinical Implications: Cognitive training that incorporates social interaction may be a promising intervention for individuals with dementia experiencing NPS.  相似文献   


8.
Purpose: To evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients combined with microvascular invasion (MVI).

Patients and methods: Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from 1st January 2000 to 31st December 2018, comparing the overall survival (OS) rates and disease-free survival (DFS) rates between postoperative adjuvant TACE and operation only for HCC patients with MVI. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size.

Results: Eight studies were enrolled in this meta-analysis, including 774 patients in the postoperative adjuvant TACE group and 856 patients in the operation only group. The pooled HR for the OS and DFS rates were significantly different between the postoperative adjuvant TACE group and the operation only group (HR 0.57, 95%CI 0.48?~?0.68, p?<?.00001; HR 0.66, 95%CI 0.58?~?0.74, p?<?.00001; respectively). However, in the subgroup analysis stratified by proportion of multiple-nodules, no significant differences were observed in the pooled HR for the OS/DFS rates between the postoperative adjuvant TACE group and the operation only group (HR 0.83, 95%CI 0.60?~?1.13, p?=?.23; HR 0.76, 95%CI 0.41?~?1.40, p?=?.37; respectively).

Conclusions: Postoperative adjuvant TACE will benefit patients with HCC and MVI, but not for multiple-HCC with MVI. However, more high-quality studies are warranted to validate the conclusion.  相似文献   


9.
Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC).

Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC.

Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750?mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires.

Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n?=?98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10–4.32) to 2.46 (1.89–4.41), p?=?.36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported.

Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC.

Abbreviations

PSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis  相似文献   


10.
Objective: This study explores how older adults respond to audiovisual virtual reality (VR) and perceive its usefulness to their lives.

Method: Focus groups were conducted with residents of a retirement community after they viewed two audiovisual VR simulations (= 41). Thematic analysis was used to identify patterns in responses.

Results: Older adults described positive and negative emotional reactions to aspects of the VR experience, articulated content preferences, shared ideas to improve the usability of the equipment, and identified facilitators and barriers that influenced perceived usefulness. Recommendations for improving this technology include maximizing the positive aspects of VR through increasing interactivity, facilitating socializing with friends or family, and enhancing older adults’ ease of use. Desired content of simulations involved travel, continuing education, reminiscence, and self-care/therapy.

Conclusion: Virtual reality was reviewed positively, yet modifications are necessary to facilitate optimal user experience and potential benefit for this population.

Clinical Implications: As older adults are interested in using VR, especially if poor health prevents the continuation of desirable activities or new experiences, it is important to respond to older adults’ preferences and remove barriers that limit use and enjoyment.  相似文献   


11.
Objective: Caring for someone with dementia can have negative consequences for caregivers, a phenomenon known as caregiver burden. Coping strategies influence the impact of caregiving-related stress. Specifically, using emotion-focused strategies has been associated with lower levels of burden, whereas dysfunctional strategies have been related to increased burden. The concept of self-compassion has been linked to both positive outcomes and the coping strategies that are most advantageous to caregivers. However, as yet, no research has studied self-compassion in caregivers. Therefore, the aim of this study was to explore the relationship between self-compassion, coping strategies and caregiver burden in dementia caregivers.

Method: Cross-sectional survey data was collected from 73 informal caregivers of people with dementia recruited from post-diagnostic support services and caregiver support groups.

Results: Self-compassion was found to be negatively related to caregiver burden and dysfunctional coping strategies and positively related to emotion-focused coping strategies. Dysfunctional strategies mediated the relationship between self-compassion and caregiver burden, whereas emotion-focused strategies did not.

Conclusion: Caregivers with higher levels of self-compassion report lower levels of burden and this is at least partly due to the use of less dysfunctional coping strategies.

Clinical Implications: Interventions that develop self-compassion could represent a useful intervention for struggling caregivers.  相似文献   


12.
Objectives: Eudaimonic well-being (EWB), increasingly recognized as a critical component of health, typically declines in later life, and there are no existing programs to sustain or increase EWB in older adults. Lighten UP! is an 8-week program to promote EWB through facilitated group sessions in community settings and at-home practice. Building on earlier pilot research, the current study assessed the effect of the Lighten UP! Program using a longitudinal, multi-site design.

Methods: Men and women (N = 169) aged 60 and over were recruited from three Wisconsin communities. EWB, life satisfaction, depression, and diverse aspects of health were assessed before and after the program and at 6-month follow up.

Results: Participants reported significantly increased EWB; these changes were maintained 6 months later. The specific EWB domains of self-acceptance, positive relations, and personal growth showed the most robust gains. Participants also showed significant and sustained declines in depressive symptoms, anxiety, and hostility.

Conclusions: Lighten UP! Program confirmed its positive effects for enhancing EWB in older adults living in multiple community settings.

Clinical Implications: Programs that sustain or enhance EWB in older adults can be expected to yield improvements in diverse aspects of mental and physical health.  相似文献   


13.
Background: Patients with amyloid light-chain (AL) amyloidosis who have advanced cardiac damage are at risk of premature mortality. Currently, bortezomib is the mainstay in the treatment of AL amyloidosis, but the benefits of bortezomib in patients with ultra-high-risk (2004 Mayo stage IIIb or 2012 Mayo stage IV) AL amyloidosis have not been proved definitively.

Methods: We performed a retrospective analysis of patients newly diagnosed with ultra-high-risk AL amyloidosis who received a bortezomib-based regimen or supportive treatment. We aimed to establish the effects of bortezomib on early mortality and long-term outcomes in this high-risk population.

Results: Patients receiving bortezomib-containing chemotherapy (n?=?62) and patients receiving no chemotherapy (n?=?24) were included. Median overall survival (OS) was 30?months in the bortezomib group and 2?months in the control group (p?<?.001), and median progression-free survival (PFS) was 15.8?months (bortezomib) and 2?months (control; p?<?.001). The early-death rate (within 6?months of treatment) was 32.3% (bortezomib) and 66.7% (control; p?<?.001). In a landmark analysis assessing outcomes in patients surviving beyond 6?months, the 2-year OS and PFS in the bortezomib group were 77.3% and 65.8%, respectively.

Conclusions: Bortezomib-based regimens can help to reduce early mortality and improve long-term survival in patients with ultra-high-risk AL amyloidosis.  相似文献   


14.
Objective: To elucidate the electrophysiological demyelinating features in patients with hereditary ATTR amyloidosis that may lead to a misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP).

Methods: In 102 patients with hereditary ATTR amyloidosis (85 Val30Met and 17 non-Val30Met; 37 and 65 from endemic and non-endemic areas, respectively), results of motor nerve conduction studies (MNCSs) with a 2-Hz low-cut filter in the unilateral ulnar and tibial nerves were retrospectively investigated to assess whether each MNCS parameter demonstrated demyelinating features that fulfil the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic (EFNS/PNS EDX) criteria for CIDP.

Results: Thirteen patients with low compound muscle action potential (CMAP) amplitude in the tibial nerve (0.7?±?0.7?mV) and prolonged distal CMAP duration in the ulnar nerve satisfied the definite EFNS/PNS EDX criteria for CIDP. Abnormal temporal dispersion and prolongation of distal latency in the tibial nerve were observed in 5 of 13 patients. However, only one of the 13 patients presented with the reduction of motor conduction velocity in each nerve. No patient exhibited conduction block in any nerve.

Conclusion: Patients with hereditary ATTR amyloidosis occasionally show electrophysiological demyelinating features without conduction block following severe axonal degeneration.  相似文献   


15.
Background: T1 mapping allows quantitative assessment of “diffuse” deposition of amyloid protein in the myocardium. Early detection of cardiac involvement and potential prognostic improvement could benefit patients with AL amyloidosis.

Objectives: This study aims to evaluate the regional variation of amyloid infiltration in the left ventricle and the prognostic value of T1 mapping in patients with AL amyloidosis.

Methods: We prospectively enrolled 77 patients with AL amyloidosis who underwent cardiac magnetic resonance on a 3.0-T scanner. Native T1 and extracellular volume (ECV) were quantitated on the basal, mid, and apical levels of the left ventricle. Late gadolinium enhancement (LGE) pattern (no or non-specific LGE, sub-endocardial LGE, and transmural LGE) was also assessed. Forty healthy subjects served as controls. The primary end point was all-cause mortality.

Results: Basal ECV (26.9?±?2.8% versus 31.1?±?4.9%, p?<?.001) were lower than apical ECV in the healthy controls; however, basal ECV (60.6?±?11.5% versus 53.0?±?9.6%, p?=?.003) were significantly higher than apical ECV in patients with transmural LGE. During the follow-up period (median duration, 28?months; 25th–75th percentile, 13.5–38.0?months), 46 patients died. Basal ECV has the largest area under the curve of 0.845 (95% CI, 0.747–0.917) to predict all-cause mortality. Multivariable Cox analysis indicated that basal ECV was an independent prognostic factor and showed incremental prognostic value beyond NYHA class, Mayo stage, and LGE pattern.

Conclusion: We demonstrated that T1 mapping may have the potential to detect a characteristic amyloid deposition with a decreasing gradient from base to apex. Furthermore, myocardial ECV indicated that basal amyloid infiltration provided robust and incremental prognostic value in patients with AL amyloidosis.  相似文献   


16.
Aims: To test the hypothesis that the fibril morphology and the fibril protein primary structure are conserved across different patients suffering from the common variant of systemic Amyloid A (AA) amyloidosis.

Methods: Amyloid fibrils were extracted from the renal tissue of four patients. The fibril morphology was analysed in negatively stained samples with transmission electron microscopy (TEM). The fibril protein identity and fragment length were determined by using mass spectrometry.

Results: The fibrils show a consistent morphology in all four patients and exhibit an average width of ~9.6?nm and an average pitch of ~112?nm. All fibrils are composed of polypeptide chains that can be assigned to human serum amyloid A (SAA) 1.1 protein. All fragments lack the N-terminal arginine residue and are C-terminally truncated. Differences exist concerning the exact C-terminal cleavage site. The most prominent cleavage site occurs at residues 64–67.

Conclusions: Our data demonstrate that AA amyloid fibrils are consistent at the level of the protein primary structure and fibril morphology in the four analysed patients.  相似文献   


17.
Objective: Many older adults cope with various chronic physical health conditions, and in some cases, with mental health and/or cognitive difficulties. Mindfulness-based interventions offer an evidence-based, mind-body complementary treatment approach for a wide range of comorbidities, yet most investigations were conducted with young or middle-aged adults. The purpose of this review was to identify randomized controlled trials (RCTs) of two leading mindfulness-based interventions conducted with older adults.

Methods: Our search of five databases identified seven RCT investigations of either Mindfulness-Based Stress Reduction (MBSR) or Mindfulness-Based Cognitive Therapy (MBCT) conducted exclusively with older adults.

Results: Results generally supported the use of MBSR for chronic low back pain, chronic insomnia, improved sleep quality, enhanced positive affect, reduced symptoms of anxiety and depression, and improved memory and executive functioning. In a sample of older adults exhibiting elevated anxiety in the absence of elevated depression, MBCT effectively reduced symptoms of anxiety.

Conclusions: This review highlights the feasibility and possible benefits of MBSR and MBCT for older adults. Additional large scale RCTs conducted with older adults coping with the range of physical, behavioral, and cognitive challenges older adults commonly face still are needed.

Clinical Implications: MBSR may be a promising intervention for older adults experiencing a variety of health concerns and possibly even cognitive decline. MBCT may reduce geriatric anxiety, although its effects on geriatric depression were not measured.  相似文献   


18.
Objectives: We aimed to externally validate Lilleness’ et al. Boston University (BU) prognostic score that replaced NT-proBNP with brain natriuretic peptide (BNP), which will allow centres without access to NT-proBNP to accurately stage and prognosticate AL amyloidosis.

Patients/methods: Forty-four were identified that had BNP, NTpro-BNP and TnI taken simultaneously, with a mean follow up of 7.3?years. Median age of the 44 patients was 67?years and 27% were female, with 61% having cardiac involvement, and 61% having renal involvement.

Results: Using the BU BNP-based staging system, we identified 12/44 (27%) of patients as stage I, 18/44 (41%) of patients as stage II and 14/44 (31%) of patients as stage III. This correlated closely with stratification via the Mayo score, with only one patient miscategorised (97.7% agreement, k?=?0.98). Median overall survival for our BU stage I was not reached, stage II was 40?months and stage III was 5?months (long rank p?=?.0012). Mayo 2004 median overall survival was identical for stages I, II and III.

Conclusion: We have provided external validation of the BU staging system, a novel prognostic scoring system incorporating BNP, instead of NT-proBNP, for AL amyloidosis.  相似文献   


19.
Objectives: Mental health factors, such as PTSD, can exacerbate typical age-related cognitive changes and lead individuals to have subjective concerns for which few interventions presently exist. This study evaluates self-reported mental health outcomes following a psychoeducational memory skills program designed for veterans over 50 with subjective memory concerns in the context of PTSD. It was hypothesized that outcomes would improve following program participation and that baseline cognitive self-efficacy would moderate improvements in self-reported depression and life satisfaction.

Methods: Veterans (n = 101, age ≥ 51) participated in an 8-week memory skills program and completed baseline and post-program assessment data as part of a quality improvement project.

Results: Life satisfaction and cognitive self-efficacy demonstrated significant improvement following participation in the memory skills program. Cognitive self-efficacy was found to significantly modify change in depressive symptoms.

Conclusions: We found improvement in mental health outcomes following participation in a psychoeducational memory skills program, with differential impact on depressive symptoms for those with low baseline cognitive self-efficacy.

Clinical Implications: Participation in this intervention led to improved life satisfaction and cognitive self-efficacy. Cognitive self-efficacy, in turn, appeared to have implications for improving depressive symptomology and may be a useful target of memory skills education.  相似文献   


20.
Objectives: We provide a review of the literature on posttraumatic stress disorder (PTSD) in older adults, focusing largely on older U.S. military veterans in two primary areas: 1) assessment and diagnosis and 2) non-pharmacological treatment of PTSD in late life.

Methods: We performed a search using PubMed and Academic Search Premier (EBSCO) databases and reviewed reference sections of selected papers. We also drew on our own clinical perspectives and reflections of seven expert mental health practitioners.

Results: Rates of PTSD are lower in older compared with younger adults. The presence of sub-syndromal/partial PTSD is important and may impact patient functioning. Assessment requires awareness and adaptation for potential differences in PTSD experience and expression in older adults. Psychotherapies for late-life PTSD appear safe, acceptable and efficacious with cognitively intact older adults, although there are relatively few controlled studies. Treatment adaptations are likely warranted for older adults with PTSD and co-morbidities (e.g., chronic illness, pain, sensory, or cognitive changes).

Conclusions: PTSD is an important clinical consideration in older adults, although the empirical database, particularly regarding psychotherapy, is limited.

Clinical Implications: Assessment for trauma history and PTSD symptoms in older adults is essential, and may lead to increased recognition and treatment.  相似文献   


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