[Pain and neurocognitive disorders: current state of the art and remaining challenges]. / Pijn en neurocognitieve stoornissen: stand van zaken en de weg nog te gaan.

The detection and treatment of pain is hampered by cognitive disorders. In this review we discuss the epidemiology of pain in cognitive disorders, and elaborate further on the current state of the art on pain in these populations. We will specifically highlight current gaps and recommendations for the future for the following knowledge domains: 1) Biology and neuropathology,  2) Assessment and evaluation, 3) Treatment and management , and 4) Contextual factors such as the organization and education.  We identify the following knowledge gaps: 1) (Biology): Do pain experience and pain expressions change in different types of cognitive disorders, and how? 2) (Assessment): How to recognize, evaluate and assess pain, in case the self-report of pain is no longer reliable? 3) (Treatment): Which treatment possibilities are effective? How can we organize this in an interdisciplinary way? And how to monitor this? How can we ensure proper implementation of pain assessment and treatment in clinical practice? Specifically with regard to non-pharmacological treatment, how can we communicate observations from different disciplines, family members and clinicians to improve the detection of pain as well as treatment monitoring/evaluation? 4) (Contextual): How can we increase knowledge and skills on pain in cognitive impairment within educational training?

The impact of pain on the course of ADL functioning in patients with dementia.

BACKGROUND: Understanding if and how pain influences activities of daily living (ADL) in dementia is essential to improving pain management and ADL functioning. This study examined the relationship between the course of pain and change in ADL functioning, both generally and regarding specific ADL functions. METHODS: Participants were Dutch nursing home residents (n = 229) with advanced dementia. ADL functioning was assessed with the Katz ADL scale, and pain with the Dutch version of the Pain Assessment Checklist for Seniors with Limited Ability to Communicate (PACSLAC-D). Changes of PACSLAC-D and Katz ADL scores were computed based on the difference in scores between baseline, 3-month and 6-month follow-up. Multivariate linear regression models were used to assess the relationships between change in pain score, change in total ADL score and specific ADL item scores during follow-up. RESULTS: At baseline, residents had a median ADL score of 18 (interquartile range 13-22, range 6-24) and 48% of the residents were in pain (PACSLAC-D ≥ 4). Residents with pain were more ADL dependent than residents without pain. A change in pain score within the first 3 months was a significant predictor for a decline in ADL functioning over the 6-month follow-up (B = 0.10, SE = 0.05, P = 0.045), and specifically, a decline on the items 'transferring' over the 6-month follow-up and 'feeding' during the first 3 months of follow-up. CONCLUSIONS: Pain is associated with ADL functioning cross-sectionally, and a change in pain score predicts a decline in ADL functioning, independent of dementia severity. Awareness of (changes in) ADL activities is clearly important and might result in both improved recognition of pain and improved pain management.

Blended Acceptance and Commitment Therapy Versus Face-to-face Cognitive Behavioral Therapy for Older Adults With Anxiety Symptoms in Primary Care: Pragmatic Single-blind Cluster Randomized Trial.

BACKGROUND: Anxiety symptoms in older adults are prevalent and disabling but often go untreated. Most trials on psychological interventions for anxiety in later life have examined the effectiveness of face-to-face cognitive behavioral therapy (CBT). To bridge the current treatment gap, other treatment approaches and delivery formats should also be evaluated. OBJECTIVE: This study is the first to examine the effectiveness of a brief blended acceptance and commitment therapy (ACT) intervention for older adults with anxiety symptoms, compared with a face-to-face CBT intervention. METHODS: Adults aged between 55-75 years (n=314) with mild to moderately severe anxiety symptoms were recruited from general practices and cluster randomized to either blended ACT or face-to-face CBT. Assessments were performed at baseline (T0), posttreatment (T1), and at 6- and 12-month follow-ups (T2 and T3, respectively). The primary outcome was anxiety symptom severity (Generalized Anxiety Disorder-7). Secondary outcomes were positive mental health, depression symptom severity, functional impairment, presence of Diagnostic and Statistical Manual of Mental Disorders V anxiety disorders, and treatment satisfaction. RESULTS: Conditions did not differ significantly regarding changes in anxiety symptom severity during the study period (T0-T1: B=.18, P=.73; T1-T2: B=-.63, P=.26; T1-T3: B=-.33, P=.59). Large reductions in anxiety symptom severity (Cohen d≥0.96) were found in both conditions post treatment, and these were maintained at the 12-month follow-up. The rates of clinically significant changes in anxiety symptoms were also not different for the blended ACT group and CBT group (χ21=0.2, P=.68). Regarding secondary outcomes, long-term effects on positive mental health were significantly stronger in the blended ACT group (B=.27, P=.03, Cohen d=0.29), and treatment satisfaction was significantly higher for blended ACT than CBT (B=3.19, P<.001, Cohen d=0.78). No other differences between the conditions were observed in the secondary outcomes. CONCLUSIONS: The results show that blended ACT is a valuable treatment alternative to CBT for anxiety in later life. TRIAL REGISTRATION: Netherlands Trial Register TRIAL NL6131 (NTR6270); https://www.trialregister.nl/trial/6131.

Patients' Use of the Internet to Find Reliable Medical Information About Minor Ailments: Vignette-Based Experimental Study.

BACKGROUND: Little is known about the exact process of how patients search for medical information on the internet and what they retrieve. There is especially a paucity of literature on browsing for information on minor ailments, a term used for harmless diseases that are very common in the general population and thus have a significant impact on health care. OBJECTIVE: This vignette-based experimental study aimed to explore what kind of Web-based search strategies are applied and how search strategies, demographic characteristics, and the quality of the visited websites relate to finding the right diagnosis. Additional goals were to describe how searching on the Web influences one's perception of the severity of the potential diagnosis and whether or not the participants would discuss the information they found on the internet with their doctors. METHODS: Out of 1372 survey participants, 355 were randomly sampled, and 155 of them were recruited and assigned to one of four clinical scenarios. Each search term they used was classified as one of three search strategies: (1) hypothesis testing, (2) narrowing within the general hypothesis area, and (3) symptom exploration. The quality of the websites used was determined by using the DISCERN instrument. To compare the diagnostic accuracy of the participants before and after the internet search, a McNemar test was used. Chi-square tests were used to describe which factors are related to the chosen search strategy. A multivariate binary logistic regression model was constructed to predict which factors are related to finding a sound diagnosis after searching the internet for health information. RESULTS: Most participants (65.8%, 102/155) used the symptom exploration strategy. However, this depends on the assigned scenario (P<.001) and the self-estimated severity score of the symptoms before the internet search (P=.001). A significant relation was found between choosing an accurate diagnosis and age (odds ratio [OR] 0.94, 95% CI 0.90 to 0.98) and the clinical scenario, as well as the use of high-quality websites (OR 7.49, 95% CI 1.85 to 30.26). Browsing the internet did not lead to a statistically significant change in participants' beliefs about the severity of the condition (McNemar test, P=.85). Most participants (65%) shared their retrieved information with their physician and most of them (75%) received a positive response. CONCLUSIONS: Our findings suggest that most patients use a symptom-based approach; however, if patients expect the potential diagnosis to be severe, they tend to use a hypothesis verification strategy more often and are therefore prone to certain forms of bias. In addition, self-diagnosing accuracy is related to younger age, the symptom scenario, and the use of high-quality websites. We should find ways to guide patients toward search strategies and websites that may more likely lead to accurate decision making.

Deprescribing preventive cardiovascular medication in patients with predicted low cardiovascular disease risk in general practice - the ECSTATIC study: a cluster randomised non-inferiority trial.

BACKGROUND: The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. METHODS: In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40-70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. RESULTS: Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ between the groups. CONCLUSIONS: The results of the ECSTATIC study show that an attempt to deprescribe preventive cardiovascular medication in low-CVD-risk patients is safe in the short term when blood pressure and cholesterol levels are monitored after stopping. An attempt to deprescribe medication can be considered, taking patient preferences into consideration. TRIAL REGISTRATION: This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ).

Subjective insomnia symptoms and sleep duration are not related to hypothalamic-pituitary-adrenal axis activity in older adults.

Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic-pituitary-adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non-depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7-8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty-two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration.

Burden of cardiovascular disease across 29 countries and GPs' decision to treat hypertension in oldest-old.

OBJECTIVES: We previously found large variations in general practitioner (GP) hypertension treatment probability in oldest-old (>80 years) between countries. We wanted to explore whether differences in country-specific cardiovascular disease (CVD) burden and life expectancy could explain the differences. DESIGN: This is a survey study using case-vignettes of oldest-old patients with different comorbidities and blood pressure levels. An ecological multilevel model analysis was performed. SETTING: GP respondents from European General Practice Research Network (EGPRN) countries, Brazil and New Zeeland. SUBJECTS: This study included 2543 GPs from 29 countries. MAIN OUTCOME MEASURES: GP treatment probability to start or not start antihypertensive treatment based on responses to case-vignettes; either low (<50% started treatment) or high (≥50% started treatment). CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due to ischemic heart disease and/or stroke and total DALYs lost per country; life expectancy at age 60 and prevalence of oldest-old per country. RESULTS: Of 1947 GPs (76%) responding to all vignettes, 787 (40%) scored high treatment probability and 1160 (60%) scored low. GPs in high CVD burden countries had higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00-4.57); in countries with low life expectancy at 60, CVD was associated with high treatment probability (OR 2.18, 95% CI 1.12-4.25); but not in countries with high life expectancy (OR 1.06, 95% CI 0.56-1.98). CONCLUSIONS: GPs' choice to treat/not treat hypertension in oldest-old was explained by differences in country-specific health characteristics. GPs in countries with high CVD burden and low life expectancy at age 60 were most likely to treat hypertension in oldest-old. Key Points • General practitioners (GPs) are in a clinical dilemma when deciding whether (or not) to treat hypertension in the oldest-old (>80 years of age). • In this study including 1947 GPs from 29 countries, we found that a high country-specific cardiovascular disease (CVD) burden (i.e. myocardial infarction and/or stroke) was associated with a higher GP treatment probability in patients aged >80 years. • However, the association was modified by country-specific life expectancy at age 60. While there was a positive association for GPs in countries with a low life expectancy at age 60, there was no association in countries with a high life expectancy at age 60. • These findings help explaining some of the large variation seen in the decision as to whether or not to treat hypertension in the oldest-old.

Pain characteristics of older persons with medically unexplained symptoms, older persons with medically explained symptoms and older persons with depression.

OBJECTIVES: The main objective of the current study is to compare chronic pain characteristics of older patients with Medically Unexplained Symptoms (MUS), to those of patients with Medically Explained Symptoms (MES), and to those of patients with Major Depressive Disorder (MDD). METHOD: By combining data from the OPUS and NESDO study, we compared pain characteristics of 102 older (>60 years) MUS-patients to 145 older MES-patients and 275 older MDD-patients in a case-control study design. Group differences were analyzed using ANCOVA, adjusted for demographic and physical characteristics. Linear regression was applied to examine the association between pain characteristics and somatization (BSI-53 somatization scale) and health anxiety (Whitely Index). RESULTS: Older MUS-patients have approximately  two times more chance of having chronic pain when compared to older MES-patients (OR = 2.01; p = .013) but equal chances as opposed to MDD-patients. After adjustments, MUS-patients report higher pain intensity and disability scores and more pain locations when compared to MES-patients, but equal values as MDD-patients. Health anxiety and somatization levels were positively associated with the number of pain sites in MUS-patients, but not with pain severity or disability. CONCLUSION: Older MUS-patients did not differ from MDD-patients with respect to any of the chronic pain characteristics, but had more intense and disabling pain, and more pain locations when compared to older MES-patients.

Correlates of sleep disturbances in depressed older persons: the Netherlands study of depression in older persons (NESDO).

OBJECTIVES: Sleep disturbances are common among depressed older persons. To gain insight into sleep disturbances in late-life depression, their occurrence and correlates were assessed. METHODS: Baseline data of 294 depressed older persons of the Netherlands Study of Depression in Older persons study were used. A diagnosis of current depression according to the diagnostic and statistical manual of mental disorders-IV (DSM-IV) was assessed with the Composite International Diagnostic Interview. Sleep disturbances were measured with the five-item Women's Health Initiative Insomnia Rating Scale, and considered present with a score of ≥10 points. RESULTS: Sleep disturbances were present in 59.9% of the depressed older persons. Bivariate linear regression analyses showed that presence of sleep disturbances was associated with fewer years of education, use of alcohol, the number of chronic diseases, higher pain intensity scores, use of more benzodiazepines, more anxiety and severity of depressive symptoms. In multivariate analyses, severity of depression appeared to be the only independent correlate. CONCLUSIONS: Sleep disturbances are highly prevalent in patients with late-life depression and independently correlated with the severity of depression. Treatment of depression may result in improvement of sleep disturbances, although cognitive behavioral interventions that focus on both depression and sleep disturbances may also be effective.

Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data.

BACKGROUND: Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands. METHODS AND FINDINGS: A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data. CONCLUSIONS: Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come.

Plasma Testosterone and the Course of Major Depressive Disorder in Older Men and Women.

OBJECTIVE: To investigate associations between testosterone levels and major depressive disorder (MDD) in older men and women. METHODS: In a cross-sectional, 2-year prospective analyses within the Netherlands Study on Depression in Older persons cohort study, 469 participants comprised 350 patients with MDD and 119 nondepressed participants in the comparison group (mean age 70.5 ± 7.3 years; 166 [35.4%] men). MDD was assessed by the Composite International Diagnostic Interview. Baseline plasma total testosterone and sex hormone binding globulin (SHBG) were assessed to calculate free testosterone. The Inventory of Depressive Symptomatology was assessed every 6 months. RESULTS: Whereas SHBG levels did not differ between the depressed/nondepressed groups (F(1,149) = 0.075, p = 0.78), men with MDD had lower mean total and free testosterone levels than the comparison group in the multivariate adjusted analyses (F(1,150) = 7.249, p = 0.008, Cohen's d = 0.51; and F(1,149) = 8.548, p = 0.004 Cohen's d = 0.55, respectively). This could be ascribed to lower testosterone in men with "pure" MDD and not in men with MDD and comorbid anxiety. Nine men (5.4%) had a total testosterone level < 8 nmol/L, of whom 8 suffered from MDD. In women, hormone levels showed no significant difference between the groups. In men (using all five measurement points during follow-up) baseline free testosterone was inversely associated with depression severity in the adjusted analyses (ß = -0.15, t(151) = -2.15, p = 0.03). CONCLUSION: Testosterone levels were lower in men with MDD compared with healthy men after adjustment for confounders, such as body mass index. No significant associations were found in women.

Estimating incidence and prevalence rates of chronic diseases using disease modeling.

BACKGROUND: Morbidity estimates between different GP registration networks show large, unexplained variations. This research explores the potential of modeling differences between networks in distinguishing new (incident) cases from existing (prevalent) cases in obtaining more reliable estimates. METHODS: Data from five Dutch GP registration networks and data on four chronic diseases (chronic obstructive pulmonary disease [COPD], diabetes, heart failure, and osteoarthritis of the knee) were used. A joint model (DisMod model) was fitted using all information on morbidity (incidence and prevalence) and mortality in each network, including a factor for misclassification of prevalent cases as incident cases. RESULTS: The observed estimates vary considerably between networks. Using disease modeling including a misclassification term improved the consistency between prevalence and incidence rates, but did not systematically decrease the variation between networks. Osteoarthritis of the knee showed large modeled misclassifications, especially in episode of care-based registries. CONCLUSION: Registries that code episodes of care rather than disease generally provide lower estimates of the prevalence of chronic diseases requiring low levels of health care such as osteoarthritis. For other diseases, modeling misclassification rates does not systematically decrease the variation between registration networks. Using disease modeling provides insight in the reliability of estimates.

Effect of chronic somatic diseases on the course of late-life depression.

OBJECTIVE: To examine the influence of specific chronic somatic diseases and overall somatic diseases burden on the course of depression in older persons. METHODS: This was a prospective cohort study with a 2-year follow-up. Participants were depressed persons (n = 285) from the Netherlands Study of Depression in Older Persons. The presence of chronic somatic diseases was based on self-report. Diagnosis of depression was assessed with the Composite International Diagnostic Interview, and severity of depression was measured with the Inventory of Depressive Symptomatology Self-report. RESULTS: Cardiovascular diseases (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.02-2.72, p = 0.041), musculoskeletal diseases (OR = 1.71, 95% CI = 1.04-2.80, p = 0.034), and the number of chronic somatic diseases (OR = 1.37, 95% CI = 1.16-1.63, p < 0.001) were associated with having a depressive disorder at 2-year follow-up. Furthermore, chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, cancer, or cumulative somatic disease burden were associated with a chronic course of depression. CONCLUSIONS: Somatic disease burden is associated with a poor course of late-life depression. The course of late-life depression is particularly unfavorable in the presence of chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, and cancer. Copyright © 2016 John Wiley & Sons, Ltd.

Validity of the three apathy items of the Geriatric Depression Scale (GDS-3A) in measuring apathy in older persons.

OBJECTIVE: The Geriatric Depression Scale (GDS)-3A, a three-item subset of the GDS-15, is increasingly used as a measure for apathy in research settings to assess factors associating with this neuropsychiatric syndrome. We aimed to assess how accurately the GDS-3A discriminates between presence and absence of apathy in two populations of community-dwelling older persons, using the Apathy Scale as reference standard. METHODS: Baseline data were used from 427 participants of the Discontinuation of Antihypertensive Treatment in Elderly people (DANTE) Study Leiden and 1118 participants of the PROactive Management Of Depression in the Elderly (PROMODE) Study, all ≥75 years and with available GDS-3A and Apathy Scale measurements. A cut-off score of ≥14 was used for presence of apathy according to the Apathy Scale. Areas under the receiver operating characteristic curve (AUC) were calculated. Based on the likelihood ratios for GDS-3A scores, a cut-off of ≥2 was used for presence of apathy according to the GDS-3A to calculate test characteristics. RESULTS: The AUC was 0.68 (95% confidence interval 0.62-0.73) in the DANTE Study and 0.72 (0.67-0.77) in the PROMODE Study. In the DANTE Study sensitivity was 29.3% (21.4-38.1) and specificity was 88.5% (84.4-91.8), whereas in the PROMODE Study sensitivity was 32.8% (24.5-41.1) and specificity 92.6% (90.9-94.2). Stratification on population characteristics did not yield more favourable test characteristics. CONCLUSION: The GDS-3A has low sensitivity and high specificity as a measure of apathy in two populations of older persons. Using the GDS-3A in research might yield estimates biassed towards the null in case of non-differential misclassification. Copyright © 2016 John Wiley & Sons, Ltd.

Variation in GP decisions on antihypertensive treatment in oldest-old and frail individuals across 29 countries.

BACKGROUND: In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision. METHODS: Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP. RESULTS: The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs' decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48-0.59; ORs per country 0.11-1.78). CONCLUSIONS: Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.

Physician's Prescribing Preference as an Instrumental Variable: Exploring Assumptions Using Survey Data.

BACKGROUND: Physician's prescribing preference is increasingly used as an instrumental variable in studies of therapeutic effects. However, differences in prescribing patterns among physicians may reflect differences in preferences or in case-mix. Furthermore, there is debate regarding the possible assumptions for point estimation using physician's preference as an instrument. METHODS: A survey was sent to general practitioners (GPs) in The Netherlands, the United Kingdom, New Zealand, Ireland, Switzerland, and Germany, asking whether they would prescribe levothyroxine to eight fictitious patients with subclinical hypothyroidism. We investigated (1) whether variation in physician's preference was observable and to what extent it was explained by characteristics of GPs and their patient populations and (2) whether the data were compatible with deterministic and stochastic monotonicity assumptions. RESULTS: Levothyroxine prescriptions varied substantially among the 526 responding GPs. Between-GP variance in levothyroxine prescriptions (logit scale) was 9.9 (95% confidence interval: 8.0, 12) in the initial mixed effects logistic model, 8.3 (6.7, 10) after adding a fixed effect for country and 8.2 (6.6, 10) after adding GP characteristics. The occurring prescription patterns falsified the deterministic monotonicity assumption. All cases in all countries were more likely to receive levothyroxine if a different case of the same GP received levothyroxine, which is compatible with the stochastic monotonicity assumption. The data were incompatible with this assumption for a different definition of the instrument. CONCLUSIONS: Our study supports the existence of physician's preference as a determinant in treatment decisions. Deterministic monotonicity will generally not be plausible for physician's preference as an instrument. Depending on the definition of the instrument, stochastic monotonicity may be plausible.

How do general practitioners identify inflammatory arthritis? A cohort analysis of Dutch general practitioner electronic medical records.

OBJECTIVE: To examine the symptoms, signs and additional investigations that general practitioners (GPs) used in the process of diagnosing recent-onset inflammatory arthritis. Here, we assumed that the recorded information was crucial in the diagnostic process of arthritis. METHODS: A database including electronic medical records of 16 Dutch general practices with 44,350 patients was studied. Patients with an episode of RA and allied conditions according to the International Classification of Primary Care-1 code L88 (here summarized as inflammatory arthritis) in the period 2009-2013 were selected. Frequencies of symptoms, signs and performed additional investigations were evaluated and compared between referred and non-referred patients. RESULTS: A total of 126 patients were diagnosed with inflammatory arthritis. Information on symptom duration, symptom location, swelling, loss of function, redness and warmth were recorded in, respectively, 64, 90, 80, 52, 48 and 41% of patients. Information on morning stiffness, family history or the squeeze-test was provided in 20, 18 and 17% of patients. Symmetry, inflammatory type arthralgia and fist closure were not recorded. Acute phase reactants and auto-antibody tests were performed in 40-46% and 8-11%, respectively. Eighty-four patients (67%) were referred to secondary care. Symptoms located in the foot, morning stiffness, family history, myalgia, absence of redness and elevated acute phase reactants were associated with referral (all P < 0.05). CONCLUSION: GPs mainly used classical signs of inflammation to diagnose inflammatory arthritis. Other items that are regularly assessed in secondary care (morning stiffness, squeeze-test, family history) were infrequently recorded by GPs.

Apathy in Older Persons With Depression: Course and Predictors: The NESDO Study.

OBJECTIVES: Apathy is a common behavioral syndrome, influencing different areas of daily functioning and often seen in depression. Little is known about the course of apathy in depression. In this study, we examine the course and predicting factors of apathy in older persons with depression. METHOD: Data of 266 older persons with depression participating in the Netherlands Study of Depression in Older Persons, all aged at least 60 years with complete Apathy Scale scores at baseline and 2-year follow-up, were included in this study. Associations between several baseline variables and severity, incidence, and persistence of apathy were examined using regression analyses. RESULTS: At 2-year follow-up, the severity of apathy was predicted by the severity of apathy at baseline, and incidence rate of apathy was 36%, with a lower baseline Mini-Mental State Examination score being an independent predictor. Older persons with incident apathy did not differ in remission rate of depression compared to those without apathy at follow-up. Persistence rate of apathy was 80% and was independently predicted by a higher baseline Apathy Scale score and, surprisingly, by less use of benzodiazepines. Persons with persistent apathy were less likely to recover from depression than those who remitted from apathy. CONCLUSION: Severity of apathy at baseline, but not depression, predicted apathy at follow-up. Incident apathy was predicted by poorer cognitive function, whereas severe apathy at baseline predicted its persistence. Remarkably, new apathy was not associated with worse outcome of depression whereas persistent apathy was.

Latent class analysis of the Apathy Scale does not identify subtypes of apathy in general population-based older persons.

OBJECTIVES: To identify clinically relevant subtypes of apathy in older persons using latent class analysis (LCA) and investigate the distribution of different characteristics across these subtypes. MEASUREMENTS: Cross-sectional data of 122 older persons (mean age 84 years, 60% female) participating in the general population-based PROactive Management Of Depression in the Elderly study, with apathy according to a score of 14 or higher on the Apathy Scale, were included for LCA. All 14 items of the Apathy Scale were used as indicator variables. Several characteristics were examined including sociodemographics, depressive, and anxiety symptoms; global cognitive function; quality of life indicators; hazardous alcohol intake (drinking ≥ 14 consumptions per week); and perceived chronic pain. RESULTS: Three distinct LCA classes were found classifying 17%, 7%, and 76% of the participants respectively. Individuals in the first class had a higher level of education and were less likely to live alone. Those in the second class had higher apathy and depression scores, lived more frequently alone and used more alcohol. Individuals in the third class showed a lower level of education and worse cognitive function. In multivariable multinomial analyses, only a lower educational level and higher scores on the Apathy Scale were significant predictors for class membership. CONCLUSION: Differences between LCA-derived classes were minimal, suggesting that in a general population-based cohort the Apathy Scale measures a homogeneous construct. Copyright © 2016 John Wiley & Sons, Ltd.

Association between pain, neuropsychiatric symptoms, and physical function in dementia: a systematic review and meta-analysis.

BACKGROUND: Pain, neuropsychiatric symptoms (NPS) and functional impairment are prevalent in patients with dementia and pain is hypothesized to be causal in both neuropsychiatric symptoms (NPS) and functional impairment. As the exact nature of the associations is unknown, this review examines the strength of associations between pain and NPS, and pain and physical function in patients with dementia. Special attention is paid to the description of measurement instruments and the methods used to detect pain, NPS and physical function. METHODS: A systematic search was made in the databases of PubMed (Medline), Embase, Cochrane, Cinahl, PsychINFO, and Web of Science. Studies were included that described associations between pain and NPS and/or physical function in patients with moderate to severe dementia. RESULTS: The search yielded 22 articles describing 18 studies, including two longitudinal studies. Most evidence was found for the association between pain and depression, followed by the association between pain and agitation/aggression. The longitudinal studies reported no direct effects between pain and NPS but some indirect effects, e.g. pain through depression. Although some association was established between pain and NPS, and pain and physical function, the strength of associations was relatively weak. Interestingly, only three studies used an observer rating scale for pain-related behaviour. CONCLUSIONS: Available evidence does not support strong associations between pain, NPS and physical function. This might be due to inadequate use or lack of rating scales to detect pain-related behaviour. These results show that the relationship between pain and NPS, as well as with physical function, is complicated and warrants additional longitudinal evaluation.