青年人群近距离工作后眼部参数的变化及恢复时间

目的：观察青年人群近距离用眼后眼部生理及功能性参数的变化及恢复时间。

方法：前瞻性研究。随机选取2019-12/2020-06在我院进行医学验光的患者69例138眼，根据主觉验光结果分为正视组(+0.75D≤等效球镜度≤-0.50D，18例36眼)、低度近视组(-0.75D≤等效球镜度≤-3.00D，25例50眼)和中度近视组(-3.25D≤等效球镜度≤-6.00D，26例52眼)。所有受试者近距离阅读20min后远眺放松20min，分别于近距离用眼前、近距离用眼20min后、远眺5、10、15、20min时测量受试者眼部生理性参数\〖前房深度(ACD)、眼轴长度(AL)\〗和功能性参数\〖正相对调节(PRA)、调节反应(BCC)\〗，分析各参数的达极时间和恢复时间。

结果：近距离用眼后眼轴变长，前房变浅，PRA绝对值变大，BCC无明显变化，75%(52/69)的受试者AL在近距离用眼20min后达极，87%(60/69)的受试者ACD在远眺5min时达极，96%(66/69)的受试者PRA在近距离用眼20min后达极，且以上参数均在远眺10min后逐渐恢复至初始状态。

结论：近距离用眼后眼部参数发生改变，眼轴变长，前房变浅，PRA绝对值增大，但均在远眺放松过程中逐渐回退，且均需要10min以上才能恢复至初始状态。     

Does the abolition of copayment increase ambulatory care utilization?: a quasi-experimental study in Germany

The European Journal of Health Economics - Due to a problematic situation with public finances, Germany introduced a copayment scheme for ambulatory care visits in 2004. In 2012, Germany achieved a...     

幽门螺杆菌感染相关因素的研究进展

幽门螺杆菌（HP）是革兰阴性微需氧的螺旋样杆菌，主要通过口-口途径在人-人之间感染传播。HP的发现加深了人类对慢性感染、炎症和癌症之间关系的认识。其特定的螺旋形体型、鞭毛及动力、尿素酶和黏附素活性，以及细胞毒素基因A（cagA）、空泡细胞毒素基因A（vacA）等是影响HP感染研究较多的相关致病因素。HP感染在胃癌的发生、发展中可能具有重要作用，但尚未确切证实HP感染是导致胃癌的主因。文章概述了HP感染相关致病因素的研究进展。     

Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2021

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children and adolescent resident in Spain, taking into account the available evidence.The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate.A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks.Rotavirus vaccine should be systematic for all infants.Meningococcal B vaccine, with a 2 + 1 schedule, should be included in routine calendar.In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups.Two-dose schedules for triple viral (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine.Universal systematic vaccination against HPV is recommended, regardless of gender, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders.     

First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric,gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis

First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Chronic acidosis rewires cancer cell metabolism through PPARα signaling

The mechanisms linking tumor microenvironment acidosis to disease progression are not understood. Here, we used mammary, pancreatic, and colon cancer cells to show that adaptation to growth at an extracellular pH (pH_e) mimicking acidic tumor niches is associated with upregulated net acid extrusion capacity and elevated intracellular pH at physiological pH_e, but not at acidic pH_e. Using metabolic profiling, shotgun lipidomics, imaging and biochemical analyses, we show that the acid adaptation-induced phenotype is characterized by a shift toward oxidative metabolism, increased lipid droplet-, triacylglycerol-, peroxisome content and mitochondrial hyperfusion. Peroxisome proliferator-activated receptor-α (PPARA, PPARα) expression and activity are upregulated, at least in part by increased fatty acid uptake. PPARα upregulates genes driving increased mitochondrial and peroxisomal mass and β-oxidation capacity, including mitochondrial lipid import proteins CPT1A, CPT2 and SLC25A20, electron transport chain components, peroxisomal proteins PEX11A and ACOX1, and thioredoxin-interacting protein (TXNIP), a negative regulator of glycolysis. This endows acid-adapted cancer cells with increased capacity for utilizing fatty acids for metabolic needs, while limiting glycolysis. As a consequence, the acid-adapted cells exhibit increased sensitivity to PPARα inhibition. We conclude that PPARα is a key upstream regulator of metabolic changes favoring cancer cell survival in acidic tumor niches.     

Perceived benefits of geriatric specialty telemedicine among rural patients and caregivers

Objective

Explore the perceived benefits of a Veterans Health Administration (VHA) geriatric specialty telemedicine service (GRECC Connect) among rural, older patients and caregivers to contribute to an assessment of its quality and value.

Data Sources

In Spring 2021, we interviewed a geographically diverse sample of rural, older patients and their caregivers who participated in GRECC Connect telemedicine visits.

Study Design

A cross-sectional qualitative study focused on patient and caregiver experiences with telemedicine, including perceived benefits and challenges.

Data Collection

We conducted 30 semi-structured qualitative interviews with rural, older (≥65) patients enrolled in the VHA and their caregivers via videoconference or phone. Interviews were recorded, transcribed, and analyzed using a rapid qualitative analysis approach.

Principal Findings

Participants described geriatric specialty telemedicine visits focused on cognitive assessments, tailored physical therapy, medication management, education on disease progression, support for managing multiple comorbidities, and suggestions to improve physical functioning. Participants reported that, in addition to prescribing medications and ordering tests, clinicians expedited referrals, coordinated care, and listened to and validated both patient and caregiver concerns. Perceived benefits included improved patient health; increased patient and caregiver understanding and confidence around symptom management; and greater feelings of empowerment, hopefulness, and support. Challenges included difficulty accessing some recommended programs and services, uncertainty related to instructions or follow-up, and not receiving as much information or treatment as desired. The content of visits was well aligned with the domains of the Age-Friendly Health Systems and Geriatric 5Ms frameworks (Medication, Mentation, Mobility, what Matters most, and Multi-complexity).

Conclusions

Alignment of patient and caregiver experiences with widely-used models of comprehensive geriatric care indicates that high-quality geriatric care can be provided through virtual modalities. Additional work is needed to develop strategies to address challenges and optimize and expand access to geriatric specialty telemedicine.