Plasma tau, neurofilament light chain and amyloid-ß levels and risk of dementia; a population-based cohort study.

CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-ß, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-ß40 and amyloid-ß42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ε4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-ß42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P < 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P < 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P < 0.0001]. Combining the lowest quartile group of amyloid-ß42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P < 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P < 0.0001], compared to the highest quartile group of amyloid-ß42 and lowest of NfL. Total-tau and amyloid-ß40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P < 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-ß42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-ß42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-ß42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia.

Health-related quality of life of people with HIV: an assessment of patient related factors and comparison with other chronic diseases.

OBJECTIVES: The health-related quality of life (HRQOL) of people with HIV is lower than in the general population, but it is unknown how it compares with that of persons with other chronic medical conditions. We compared HRQOL in HIV with HRQOL in diabetes mellitus type 1, diabetes mellitus type 2 and rheumatoid arthritis (RA). In addition, we investigated factors associated with HRQOL in HIV. DESIGN: Cross-sectional study. METHODS: HRQOL was measured with the Medical Outcomes Study Short Form 36-item Health Survey in a nationwide sample of people with HIV in care in the Netherlands and on combination antiretroviral therapy for at least 6 months. We added data from studies in diabetes mellitus types 1 and 2, and RA. Logistic regression analysis was used to examine: the association between disease group and a poor HRQOL, and patient factors associated with poor HRQOL in HIV. RESULTS: The odds of a poor physical HRQOL in the HIV group were comparable with the odds in diabetes mellitus types 1 and 2, but lower than in RA patients. The odds of a poor mental HRQOL in HIV were higher than in the other groups. In HIV, a history of AIDS, longer duration of combination antiretroviral therapy and severe comorbidity were associated with a poor physical HRQOL. Sub-Saharan African descent and CD4 cell count of less than 350 cells/µl were associated with poor mental HRQOL. CONCLUSION: People with HIV were more likely to have a poor mental HRQOL than patients with other chronic conditions. Addressing mental health should be an integral part of outpatient HIV care.

Satisfaction of well-controlled type 2 diabetes patients with three-monthly and six-monthly monitoring.

BACKGROUND: Patient's satisfaction with monitoring frequency is of interest when implementing six-monthly monitoring for well-controlled type 2 diabetes patients. Here we want to determine the satisfaction of well-controlled type 2 diabetes patients with either three-monthly or six-monthly diabetes monitoring and their future preference. METHODS: Survey among 2215 well-controlled type 2 diabetes patients (not using insulin, HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg and total cholesterol ≤5.2 mmol/l) who participated in the EFFIMODI study, a randomised controlled patient-preference equivalence trial. At baseline, participants were asked whether they had a strong preference for three-monthly or six-monthly monitoring or not. If not, they were randomised to either three-monthly or six-monthly monitoring, while the others were monitored according to their preference. After eighteen months, all participants were asked whether they were satisfied with the monitoring frequency and about their future preference. Patient characteristics associated with satisfaction were also examined. RESULTS: Most patients (70.8%) would like to continue their monitoring frequency. Patients from the preference groups were more often satisfied than randomised patients (92.7% and 88.1%, respectively) and patients monitored three-monthly were more often satisfied than patients monitored six-monthly (93.5% and 88.5%, respectively). Higher age, better physical health, less diabetes-related distress, higher diabetes treatment satisfaction and less perceived hyper- and hypoglycaemias were associated with a higher monitoring satisfaction. CONCLUSIONS: Most well-controlled type 2 diabetes patients were satisfied with their monitoring frequency and would like to continue it. Although the satisfaction for three-monthly monitoring was slightly higher, the satisfaction with six-monthly monitoring was still rather high (88.5%). TRIAL REGISTRATION: Current controlled trials ISRCTN93201802.

Six-monthly diabetes monitoring of well-controlled patients: experiences of primary care providers.

AIMS: To examine experiences of primary care providers with six-monthly diabetes monitoring of well-controlled patients. METHODS: This study was part of the EFFIMODI study, examining whether six-monthly monitoring of well-controlled (HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg and total cholesterol ≤5.2 mmol/l) type 2 diabetes patients results in equivalent cardiometabolic control compared to three-monthly monitoring. Primary care providers completed a questionnaire about their experiences with six-monthly diabetes monitoring, whether they want to continue six-monthly monitoring and for which type of patients six-monthly monitoring is sufficient. RESULTS: Of 163 questionnaires, 157 (96.3%) were completed and returned. Only 14 (8.9%) primary care providers were negative about the six-monthly monitoring and 102 (65.0%) would like to continue six-monthly monitoring. Primary care providers disagreed about patients' ability to determine their own monitoring frequency and whether six-monthly monitoring was suitable for all well-controlled type 2 diabetes patients. Practical concerns emerged such as the inability to declare healthcare costs and the unsuitability of electronic health record systems. CONCLUSIONS: Almost two out of three primary care providers would like to continue six-monthly monitoring of well-controlled type 2 diabetes patients. However, some diabetes care providers should be convinced and some practical concerns should be solved.

Both cardiovascular and non-cardiovascular comorbidity are related to health status in well-controlled type 2 diabetes patients: a cross-sectional analysis.

BACKGROUND: Type 2 diabetes patients have a decreased health-related quality of life compared to healthy persons, especially regarding physical functioning and well-being. Health-related quality of life is even lower in type 2 diabetes patients when other diseases co-exist. In contrast to earlier studies, we assessed the associations between the number and type of comorbidities and health status in well-controlled type 2 diabetes patients, in whom treatment goals for HbA1c, blood pressure and cholesterol had been reached. Approximately one in five type 2 diabetes patients belongs to this group. METHODS: Cross-sectional analysis was performed in 2086 well-controlled (HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg, total cholesterol ≤5.2 mmol/l and not using insulin) type 2 diabetes patients in general practice. Both number and type (cardiovascular and non-cardiovascular) of comorbidities were determined for each patient. Health status was assessed with the questionnaires Short Form-36 (SF-36) and EuroQol (EQ). The SF-36 generates eight dimensions of health and a Physical and Mental Component Score (PCS and MCS), scale: 0-100. The EQ consists of two parts: EQ-5D and EQ Visual Analogue Scale. Multivariable linear regression analysis was used to assess if number and type of comorbidities were associated with health status. RESULTS: Well-controlled type 2 diabetes patients with comorbidities had a much lower health status, with a decrease ranging from -1.5 for the MCS to -26.3 for role limitations due to physical problems, compared to those without. Health status decreased when the number of comorbidities increased, except for mental health, role limitations due to emotional problems, MCS and both EQ measures. In patients with both cardiovascular and non-cardiovascular comorbidity, physical functioning, role limitations due to physical problems and PCS were significantly lower than in patients with only cardiovascular comorbidity. Physical functioning was also lower compared to patients with only non-cardiovascular comorbidity. CONCLUSIONS: Even acceptable values of HbA1c, blood pressure and cholesterol in type 2 diabetes patients are not necessarily related with a good health status. We have shown that comorbidities have a large impact on health status. Physicians may take into account patient's health status and integrate the impact of comorbidities into diabetes care.

Recreational drug use during sex and sexually transmitted infections among clients of a city sexually transmitted infections clinic in Amsterdam, the Netherlands.

BACKGROUND: Recreational drug use is associated with high-risk sexual behavior and sexually transmitted infections (STIs). We assessed the prevalence of drug use during sex and the associations between such use and STI (chlamydia, gonorrhea, or syphilis). METHODS: During 3 periods in 2008 and 2009, attendees of an STI clinic in Amsterdam were interviewed about sexual behavior and drug use during sex and tested for STI. Associations between sex-related drug use and STI were assessed separately for heterosexual men, men who have sex with men (MSM), and women. We examined whether drug use was associated with STI after adjusting for high-risk sexual behavior. RESULTS: Nine hundred sixty-one heterosexual men, 673 MSM, and 1188 women participated in this study. Of these, 11.9% had chlamydia, 3.4% gonorrhea, and 1.2% syphilis. Sex-related drug use in the previous 6 months was reported by 22.6% of heterosexual men, 51.6% of MSM, and 16.0% of women. In multivariable analyses, adjusting for demographics (and high-risk sexual behavior in MSM), sex-related drug use was associated with STI in MSM (any drugs and poppers) and women (GHB and XTC) but not in heterosexual men. Stratified analysis in MSM showed that sex-related use of poppers was associated with STI in HIV-negative MSM but not in HIV-infected MSM. CONCLUSION: Clients reported frequent sex-related drug use, which was associated with STI in MSM and women. In MSM, sex-related drug use was associated with STI after adjusting for high-risk sexual behavior but only in HIV-negative MSM. Prevention measures targeted at decreasing sex-related drug use could reduce the incidence of STI.

Towards a more efficient diabetes control in primary care: six-monthly monitoring compared with three-monthly monitoring in type 2 diabetes - The EFFIMODI trial. Design of a randomised controlled patient-preference equivalence trial in primary care.

BACKGROUND: Scientific evidence for the frequency of monitoring of type 2 diabetes patients is lacking. If three-monthly control in general practice could be reduced to six-monthly control in some patients, this would on the one hand reduce the use of medical services including involvement of practice nurses, and thus reduce costs, and on the other hand alleviate the burden of people with type 2 diabetes. The goal of this study is to make primary diabetes care as efficient as possible for patients and health care providers. Therefore, we want to determine whether six-monthly monitoring of well-controlled type 2 diabetes patients in primary care leads to equivalent cardiometabolic control compared to the generally recommended three-monthly monitoring. METHODS AND DESIGN: The study is a randomised controlled patient-preference equivalence trial. Participants are asked if they prefer three-monthly (usual care) or six-monthly diabetes monitoring. If they do not have a preference, they are randomised to a three-monthly or six-monthly monitoring group. Patients are eligible for the study if they are between 40 and 80 years old, diagnosed with type 2 diabetes more than one year ago, treated by a general practitioner, not on insulin treatment, and with HbA1c < or = 7.5%, systolic blood pressure < or = 145 mmHg and total cholesterol < or = 5.2 mmol/l. The intervention group (six-monthly monitoring) will receive the same treatment with the same treatment targets as the control group (three-monthly monitoring). The intervention period will last one and a half year. After the intervention, the three-monthly and six-monthly monitoring groups are compared on equivalence of cardiometabolic control. Secondary outcome measures are HbA1c, blood pressure, cholesterol level, Body Mass Index, smoking behaviour, physical activity, loss of work due to illness, health status, diabetes-specific distress, satisfaction with treatment and adherence to medications. We will use intention-to-treat analysis with repeated measures. For outcomes that have only baseline and final measurements, we will use ANCOVA. Depending on the results, a cost-minimisation analysis or an incremental cost-effectiveness analysis will be done. DISCUSSION: This study will provide valuable information on the most efficient control frequency of well-controlled type 2 diabetes patients in primary care.