Perceptions of Frail Older Adults on Contributing Factors Causing the Onset of Crises Leading to Hospital Admissions: A Qualitative Study.

Aim: To explore frail older people's perceptions of factors contributing to a health crisis, describe similarities and depict these in a chronological, aggregated patient journey map.

Design: An exploratory-descriptive qualitative study.

Methods: Frail older patients visiting the emergency department of a metropolitan academic hospital in the Netherlands during the first 6 months of 2021 were recruited by purposive sampling.

Assessing dynamical resilience indicators in older adults: a prospective feasibility cohort study.

Purpose: Measuring dynamical resilience indicators based on time series data may improve the prediction of health deterioration in older adults after hospital discharge. We examined the feasibility of an intensive prospective cohort study examining dynamical resilience indicators based on time series data of symptoms and physical activity in acutely ill older adults who visited the Emergency Department (ED).

Methods: This is a prospective cohort study with time series data from symptom questionnaires and activity trackers.

Investigating the Effectiveness of Care Delivery at an Acute Geriatric Community Hospital for Older Adults in the Netherlands: A Prospective Controlled Observational Study.

Objectives: Hospital admission in older adults is associated with unwanted outcomes such as readmission, institutionalization, and functional decline. To reduce these outcomes, the Netherlands introduced an alternative to hospital-based care: the Acute Geriatric Community Hospital (AGCH). The AGCH is an acute care unit situated outside of a hospital focusing on early rehabilitation and comprehensive geriatric assessment.

Post-discharge light physical activity indicates recovery in acutely hospitalized older adults - the Hospital-ADL study.

Background: Physical activity (PA) levels might be a simple overall physical function indicator of recovery in acutely hospitalized older adults; however it is unknown which amount and level of PA is associated with recovery. Our objective was to evaluate the amount and level of post discharge PA and its optimum cut-off values associated with recovery among acutely hospitalized older adults and stratified for frailty.

Methods: We performed a prospective observational cohort study including acutely hospitalized older adults (≥ 70 years).

Older patients' perspectives on factors contributing to frequent visits to the emergency department: a qualitative interview study.

Background: Older patients are at high risk of unplanned revisits to the emergency department (ED) because of their medical complexity. To reduce the number of ED visits, we need more knowledge about the patient-level, environmental, and healthcare factors involved. The aim of this study was to describe older patients' perspectives and experiences before and after an ED visit, and to identify factors that possibly contribute to frequent ED revisits.

Physical Resilience in Daily Functioning Among Acutely Ill Hospitalized Older Adults: The Hospital-ADL Study.

Objectives: Insight into older adults' physical resilience is needed to predict functional recovery after hospitalization. We assessed functional trajectories in response to acute illness and subsequent hospitalization and investigated baseline variables and dynamic variables associated with these trajectories.

Design: Prospective observational cohort study (Hospitalization-Associated Disability and impact on daily Life Study).

Factors Associated with Step Numbers in Acutely Hospitalized Older Adults: The Hospital-Activities of Daily Living Study.

Objectives: To determine the number of steps taken by older patients in hospital and 1 week after discharge; to identify factors associated with step numbers after discharge; and to examine the association between functional decline and step numbers after discharge.

Design: Prospective observational cohort study conducted in 2015-2017.

Setting And Participants: Older adults (≥70 years of age) acutely hospitalized for at least 48 hours at internal, cardiology, or geriatric wards in 6 Dutch hospitals.

Feasibility of couple-based expanded carrier screening offered by general practitioners.

Expanded carrier screening (ECS) aims to inform couples' reproductive choice, preferably before conception. As part of an implementation study in which trained general practitioners (GPs) offered a population-based ECS couple-test, we evaluated the feasibility of the test-offer and degree of participant informed choice (IC). Trained GPs from nine practices in the northern Netherlands invited 4295 female patients aged 18-40 to take part in couple-based ECS.

Ovarian cancer in BRCA1/2 mutation carriers: The impact of mutation position and family history on the cancer risk.

Objectives: Assessing the combined impact of mutation position, regarding the ovarian cancer cluster region (OCCR), and type of cancer family history (FH) on age-related penetrance of ovarian cancer (OC) in women from BRCA1/2 families from the northern Netherlands.

Study Design: A consecutive series of 1763 mutation carriers and their first-degree relatives from 355 proven BRCA1/2 families with a history of breast and/or ovarian cancer with in total 248 OC cases was included. Mutations were stratified for gene (BRCA1 or BRCA2) and location (within or outside the OCCR).

Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know.

We explored the dilemma between patients' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation.

Variation in mutation spectrum partly explains regional differences in the breast cancer risk of female BRCA mutation carriers in the Netherlands.

Background: We aimed to quantify previously observed relatively high cancer risks in BRCA2 mutation carriers (BRCA2 carriers) older than 60 in the Northern Netherlands, and to analyze whether these could be explained by mutation spectrum or population background risk.

Methods: This consecutive cohort study included all known pathogenic BRCA1/2 carriers in the Northern Netherlands (N = 1,050). Carrier and general reference populations were: BRCA1/2 carriers in the rest of the Netherlands (N = 2,013) and the general population in both regions.

Proven non-carriers in BRCA families have an earlier age of onset of breast cancer.

Background: Risk estimates for proven non-carriers in BRCA mutation families are inconsistent for breast cancer and lacking for ovarian cancer. We aimed to assess the age-related risks for breast and ovarian cancer for proven non-carriers in these families.

Methods: A consecutive cohort study ascertained 464 proven non-carriers who had a first-degree relative with a pathogenic BRCA mutation.

Breast Cancer Incidence After Risk-Reducing Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers.

Premenopausal risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 mutation carriers effectively reduces ovarian cancer risk, but also reduces breast cancer risk. Breast cancer risk reductions up to 50% have been reported for both BRCA1 and BRCA2 mutation carriers, but recent prospective studies were not able to reproduce this finding for BRCA1 mutation carriers. Breast cancer incidence after RRSO was assessed in a consecutive series of 104 BRCA1 and 58 BRCA2 mutation carriers.

Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.

Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age.

Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the general population in this region. We identified 1188 female mutation carriers and first-degree female relatives in 185 families with a pathogenic BRCA1 or BRCA2 mutation.

An electronic regulatory document management system for a clinical trial network.

A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials.

Dengue viremia in blood donors from Honduras, Brazil, and Australia.

Background: Dengue fever and hemorrhagic disease are caused by four dengue virus (DENV) serotypes (DENV-1 to -4), mosquito-borne flaviviruses with increasing incidence, and expanding global distributions. Documented transfusion transmission of West Nile virus raised concern regarding transfusion-transmitted DENV.

Methods: A DENV RNA assay was developed based on transcription-mediated amplification (TMA) blood screening assays routinely used by blood centers worldwide.

Establishing long-term cultures with self-renewing acute myeloid leukemia stem/progenitor cells.

Objective: With the emergence of the concept of the leukemia stem cell, assays to study them remain pivotal in understanding (leukemic) stem cell biology.

Methods: We have cultured acute myeloid leukemia CD34(+) cells on bone marrow stroma. Long-term expansion was monitored and self-renewal was addressed by replating of Leukemic-cobblestone area-forming cells (L-CAs).

A cross-sectional study of a prototype carcinogenic human papillomavirus E6/E7 messenger RNA assay for detection of cervical precancer and cancer.

Purpose: To evaluate carcinogenic human papillomavirus (HPV) mRNA for E6 and E7 mRNA detection on clinical specimens to identify women with cervical precancer and cancer.

Experimental Design: We evaluated a prototype assay that collectively detects oncogenes E6/E7 mRNA for 14 carcinogenic HPV genotypes on a sample of liquid cytology specimens (n=531), masked to clinical data and to the presence of HPV genotypes detected by PGMY09/11 L1 consensus primer PCR assay.

Results: We found an increasing likelihood of testing positive for carcinogenic HPV E6/E7 mRNA with increasing severity of cytology (P(Trend) < 0.

Improving osteoporosis screening: results from a randomized cluster trial.

Background: Despite recommendations, osteoporosis screening rates among women aged 65 years and older remain low. We present results from a clustered, randomized trial evaluating patient mailed reminders, alone and in combination with physician prompts, to improve osteoporosis screening and treatment.

Methods: Primary care clinics (n = 15) were randomized to usual care, mailed reminders alone, or mailed reminders with physician prompts.

Selective expression of cholesterol metabolism genes in normal CD34+CD38- cells with a heterogeneous expression pattern in AML cells.

Objective: To identify adenosine triphosphate-binding-cassette (ABC) transporters that are selectively expressed in normal and/or leukemic CD34+CD38- stem cells.

Methods: Microarray experiments on murine stem cells identified 13 ABC transporters with a high expression level. Corresponding human transporters were analyzed in normal CD34+CD38- and CD34+CD38+ bone marrow cells by quantitative reverse transcriptase polymerase chain reaction.

Evaluation of a new molecular assay for detection of human immunodeficiency virus type 1 RNA, hepatitis C virus RNA, and hepatitis B virus DNA.

Background: Rapid, sensitive, specific, and cost-effective screening of donated blood to prevent transmission of infectious agents remains challenging. In recent years, incorporation of nucleic acid testing for HIV-1 and HCV RNA improved blood safety by reducing the window period between infection and serologic detection. For HBV infection, this window period with most serologic assays is 50-60 days.

Breast cancer resistance protein (BCRP) in acute leukemia.

Multidrug resistance, cross-resistance to structurally and functionally unrelated drugs, is an important cause of treatment failure in acute leukemia. Multidrug resistance can result from the overexpression of ATP-dependent efflux pumps, such as P-glycoprotein and members of the multidrug resistance associated protein (MRP) family. Recently a novel transporter has been identified, which is called breast cancer resistance protein (BCRP), ABCG2 or mitoxantrone resistance protein.

Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation.

The aim of this study was to find factors that could explain the accumulation difference of mitoxantrone in the BCRP1-negative GLC4-MITO cell line compared to GLC4. Comparative genomic hybridisation (CGH) was applied to determine chromosomal differences between GLC4 and GLC4-MITO. Comparative genomic hybridisation analysis revealed gain of 2q, 6p, 9q, 13q, 14q, 15q, 19q and Xp and loss of 1p, 2q, 3p, 3q, 4q, 6q, 8q, 11p, 16p, 17q, 18p, 20p and Xq.

The role of breast cancer resistance protein in acute lymphoblastic leukemia.

Purpose: Overexpression of the transporter ABCG2, also known as breast cancer resistance protein and mitoxantrone resistance protein, can confer resistance to a variety of cytostatic drugs, such as mitoxantrone, topotecan, doxorubicin, and daunorubicin. This study analyzes the ABCG2 expression and activity in 46 human de novo acute lymphoblastic leukemia B- and T-lineage (ALL) samples.

Experimental Design: ABCG2 expression was measured flow cytometrically with the BXP-34 monoclonal antibody.