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Background Children with overweight and obesity in socially deprived areas (SDAs) are less likely to complete and be compliant to a weight-loss programme. Objectives To identify factors associated with dropout and compliance of a multidisciplinary weight-loss programme in SDA. Methods This prospective longitudinal cohort study included children (6–12 years) with overweight and obesity in a 12-week multidisciplinary intervention living in SDA in Rotterdam, the Netherlands. Potential predictive variables for dropout and compliance included were age, sex, the weight of the child and parents, quality of life, and referral status (self-registration or referral). A Cox proportional hazards model was performed to study the association between dropout and its potential predictive variables, whereas logistic regression analyses were used for the potential predictors for compliance. Results A total of 121 children started the intervention programme. Forty-one (33.9%) children dropped out and 68 (56.2%) were compliant with the intervention. The risk of dropping out of the intervention was significantly lower for a child with overweight parents than for those with parents with normal weight (adjusted hazard ratio [HR] 0.22 [95% confidence interval, CI 0.063–0.75]), and for those with parents with obesity (adjusted HR 0.18 [95% CI 0.060–0.52]). No other potential predictive variables were associated with dropout or compliance. Conclusion Children from SDA participating in a weight-loss programme have a relatively high dropout and a low compliance rate. Parental weight seems to be an important predictor for dropout of children from SDA, where children with normal weight or obese parents have the highest risk of dropout compared with children of overweight parents.

To explore characteristics of nocturnal pain and to identify differences in participants' characteristics and osteoarthritis (OA) symptoms between hip and knee OA participants with and without nocturnal pain.Data for this exploratory cross-sectional study were obtained from an online survey, distributed through social media and patient associations in the period from April 2020 until May 2020, which was conducted in 101 participants with (self-reported) hip or knee OA. Descriptive statistics were used to provide insight into the characteristics of the study population. Pain intensity, localization, dimension, and impact of (nocturnal) pain on sleep were described and compared with daytime pain.Nocturnal pain was reported by 76/101 (75%) participants. Participants with nocturnal pain scored higher visual analogue scale (VAS) scores for their nocturnal pain compared with their pain at the moment (respectively: median VAS score 49.5 vs. 40.0). Their day pain rating indexes of sensory-discriminative dimension were higher compared with their nocturnal pain. Comparison between participants with and without nocturnal pain showed that participants with nocturnal pain were affected by intermittent, constant, and radiating pain. Pain had more impact on their sleep and they scored their pain at its worst higher compared with participants without nocturnal pain.In participants with nocturnal pain (75%), we found that their VAS pain scores were not in harmony with their pain expressed in words. This study increases awareness of nocturnal pain in OA patients in general practice. More research is needed to provide general practitioners possible interventions for patients with OA and nocturnal pain.Nocturnal pain is an important part of the pain experience in osteoarthritis (OA) and highlighted as key concern by patients with hip and knee OA. Reports have shown a wide range in prevalence of nocturnal hip and knee pain in OA patients (14%–85%). We found that participants with nocturnal pain (76/101 = 75%) were more often affected by both intermittent and constant pain, reported higher pain scores for pain at its worst and pain had more impact on their sleep compared with those without nocturnal pain. Participants with nocturnal pain scored higher visual analogue scale (VAS) scores for their nocturnal pain compared with their pain at the moment. On the other hand, they scored the pain expressed in words higher for their day pain than for their nocturnal pain. More research is needed to explore factors that associate with nocturnal pain and to explore how healthcare professionals can support people with nocturnal pain.

To evaluate the prevalence during a 10-year follow-up of clinically relevant fluctuations in pain and the course of hip pain in participants with hip complaints suspected to be early stage hip osteoarthritis (OA). To distinguish between participants with relevant fluctuations in pain and those without based on baseline characteristics.Data were collected at baseline and after 2, 5, 8, and 10 years on 495 participants from the Cohort Hip and Cohort Knee Study (CHECK) with hip pain at baseline. Baseline demographic, anamnestic, and physical-examination characteristics were assessed. The primary outcome was levels of pain in the past week (scored using 0-10 Numeric Rating Scale) at follow-up assessments. Relevant fluctuation was defined as average absolute residuals greater than 1 after fitting a straight line to the participant's pain scores over time.The majority of the participants (76%) had stable or decreasing pain. Relevant fluctuations were found in 37% of the participants. The following baseline variables were positively associated with the presence of relevant fluctuations: higher levels of pain in the past week, use of pain transformation as a coping style, higher number of comorbidities, use of pain medication, and higher levels of high-sensitivity C-reactive protein. No associations were found for baseline radiographic hip OA or clinical hip OA.During a 10-year follow-up, the majority of participants had stable or decreasing pain levels. In those participants with relevant fluctuation (37%), a limited number of baseline variables were associated with increased odds of having relevant fluctuations in pain.Pain appears to be an important reason for consulting the general practitioner (GP) for hip osteoarthritis (OA) complaints. We know that hip pain remained quite stable over 10 years. Also is known that there is considerable variety between patients in pain. In this study, we found relevant pain fluctuations in 37% of primary care patients with hip complaints over a period of 10 years. The pain fluctuation was not associated with having osteoarthritis, neither radiographic hip OA (diagnosed based on a X-ray) or clinical hip OA (determined according to the American College of Rheumatology (ACR) criteria) at baseline. More research is needed to discover why some people experience fluctuations in time than others.

Objective: To determine the incidence and prevalence of knee osteoarthritis (OA) using codified and narrative data from general practices throughout The Netherlands. Methods: This retrospective cohort study was conducted using the Integrated Primary Care Information database. Patients with codified knee OA were selected, and an algorithm was developed to identify patients with narratively diagnosed knee OA only. Point prevalence proportions and incidence rates among people age ≥30 years were assessed from 2008 to 2019. The association of comorbidities with codified knee OA was analyzed using multivariable logistic regression. Results: The positive predicted value of narratively diagnosed knee OA only was 94.0% (95% confidence interval [95% CI] 87.4–100%) and for codified knee OA 96.0% (95% CI 90.6–100%). Including narrative data in addition to codified data resulted in a prevalence 1.83–2.01 times higher (over the study years); prevalence increased from 5.8% to 11.8% between 2008 and 2019. The incidence rate was 1.93–2.28 times higher and increased from 9.98 per 1,000 person-years to 13.8 per 1,000 person-years between 2008 and 2019. Among patients with codified knee OA, 39.4% were previously diagnosed narratively with knee OA, on average ~3 years earlier. Comorbidities influenced the likelihood of being recorded with codified knee OA. Conclusion: Our study of a Dutch primary care database showed that current incidence and prevalence estimates based on codified data alone from electronic health records are underestimated. Narrative data can be incorporated in addition to codified data to identify knee OA patients more accurately.

Objective: To assess the effectiveness of duloxetine in addition to usual care in patients with chronic osteoarthritis (OA) pain. The cost-effectiveness and whether the presence of symptoms of centralized pain alters the response to duloxetine were secondary objectives. Methods: We conducted an open-label, cluster-randomized trial. Patients with chronic hip or knee OA pain who had an insufficient response to acetaminophen and nonsteroidal antiinflammatory drugs were included. Randomization took place at the general practice level, and patients received duloxetine (60 mg/day) in addition to usual care or usual care alone. The presence of centralized pain was defined as a modified PainDETECT Questionnaire score >12. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores (scale 0–20) at 3 months after the initiation of treatment. Our aim was to detect a difference between the groups of a clinically relevant effect of 1.9 points (effect size 0.4). We used a linear mixed model with repeated measurements to analyze the data. Results: In total, 133 patients were included, and 132 patients were randomized into treatment groups. A total of 66 patients (at 31 practices) were randomized to receive duloxetine in addition to usual care, and 66 patients (at 35 practices) were randomized to receive usual care alone. We found no differences in WOMAC pain scores between the groups at 3 months (adjusted difference –0.58 [95% confidence interval (95% CI) –1.80, 0.63]) or at 12 months (adjusted difference –0.26 [95% CI –1.86, 1.34]). In the subgroup of patients with centralized pain symptoms, we also found no effect of duloxetine compared to usual care alone (adjusted difference –0.32 [95% CI –2.32, 1.67]). Conclusion: We found no effect of duloxetine added to usual care compared to usual care alone in patients with chronic knee or hip OA pain. Another trial including patients with centralized pain symptoms should be conducted to validate our results.

BackgroundOsgood–Schlatter disease (OSD) is a non-traumatic knee problem that is primarily observed in sports-active children and adolescents aged 8–15 years.AimTo determine the incidence of OSD and to gain an insight into the management of children and adolescents with OSD in general practice.Design and settingA retrospective cohort study was conducted using a healthcare database containing full electronic health records of over 200 000 patients in general practice in and around the Dutch city of Rotterdam.MethodPatients with a new diagnosis of OSD from 1 January 2012 to 31 December 2017 were extracted using a search algorithm based on International Classification of Primary Health Care coding and search terms in free text. Data on the management of OSD were manually interpreted.ResultsThe mean incidence over the study period was 3.8 (95% confidence interval [CI] = 3.5 to 4.2) per 1000 person–years in those aged 8–18 years. Boys had a higher incidence rate of 4.9 (95% CI = 4.3 to 5.5) compared with girls (2.7, 95% CI = 2.3 to 3.2). Peak incidence was at 12 years of age for boys and 11 years for girls. Advice was the most commonly applied strategy (55.1%), followed by rest (21.0%), referral for imaging (19.5%), and physiotherapy (13.4%).ConclusionTo the authors’ knowledge, for the first time the incidence of OSD has been calculated using GP electronic medical files. There is a discrepancy, especially for imaging and referral to a medical specialist, between the current Dutch general practice guidelines and how GPs actually manage the condition in clinical practice.

Background An increase in the demand for general practitioners is expected in many countries, but only a minority of medical students consider a career in general practice. More detailed and up-to-date knowledge about medical student’s perception of general practice would be helpful for efforts to encourage medical students to consider a career in general practice. Methods We performed a cross-sectional single center survey among Dutch medical students to evaluate their perception of general practice at three different stages in their study: Ba1: first-year bachelor students; Ba3: third-year bachelor students; Ma3: third-year master students. The impact of different factors on their attitudes and perceptions was quantified. A multivariate logistic regression was performed with ‘interest in general practice’ as the outcome variable. Results The median age for Ba1 was 18 (IQR: 18–19) and 71.5% were female, for Ba3 the median age was 20 (IQR: 20–21) and 70.6% were female and for Ma3 the median age was 25 years (IQR: 24–26) and 73.3% were female. On average, 31.2% of the respondents had a migration background. The mean response rate for this study was 77.1%. Of the participating Ba1 students (n = 340) only 22.4% considered working as a GP after medical school; for Ba3 students (n = 231) this percentage was 33.8%, and for Ma3 students (n = 210) it was significantly higher at 70.5%; in the final multivariate model this corresponded to an odds ratio (OR) of 4.3 (95%-CI:2.6–6.9) compared to Ba1 students. The strongest predictor in the final model was the opinion that general practice provides a pleasant working environment (OR 9.5; 95%-CI: 6.2–14.5). Conclusion This study showed that multiple factors are significantly related to medical students’ interest in general practice. Although students believed that general practice does not have a high status within the medical profession, they acknowledged the social importance and the pleasant working environment of general practice. Knowledge obtained in this study can be used when designing a medical curriculum or a general practice course.

Background Anemia can be categorized into micro-, normo- or macrocytic anemia based on the mean corpuscular volume (MCV). This categorization might help to define the etiology of anemia. Methods The cohort consisted of patients newly diagnosed with anaemia in primary care. Seven aetiologies of anaemia were defined, based on an extensive laboratory protocol. Two assumptions were tested: (i) MCV 100 fl (macrocytic) excludes iron deficiency anaemia, anaemia of chronic disease and renal anaemia as anaemia aetiology. Results Data of 4129 patients were analysed. One anaemia aetiology could be assigned to 2422 (59%) patients, more than one anaemia aetiology to 888 (22%) patients and uncertainty regarding the aetiology remained in 819 (20%) patients. MCV values were within the normal range in 3505 patients (85%). In 59 of 365 microcytic patients (16%), the anaemia aetiology was not in accordance with the first assumption. In 233 of 259 macrocytic patients (90%), the anaemia aetiology was not in accordance with the second assumption. Conclusions Anaemia aetiologies might be ruled out incorrectly if MCV guided classification is used as a first step in the diagnostic work-up of anaemia. We recommend using a broader set of laboratory tests, independent of MCV.

ObjectivesTo evaluate the cost-effectiveness of custom-made insoles compared with general practitioner (GP)-led usual care after 26 weeks of follow-up in individuals with plantar heel pain (PHP) from a societal perspective.DesignCost-effectiveness analysis of a double-blinded randomised controlled trial.SettingGeneral practice in the Netherlands.Participants116 participants with PHP for at least 2 weeks, aged 18–65 years and presenting to the GP.InterventionsParticipants were randomised to GP-led usual care (n=46) or referral to a podiatrist for treatment with a custom-made insole (n=70). Participant randomised to a sham insole (n=69) were excluded from this analysis.Primary and secondary outcomesOutcomes comprised pain during rest and activity, and quality of life. Costs included healthcare and lost productivity costs. Statistical uncertainty was estimated using bootstrapping and presented using cost-effectiveness acceptability curves.ResultsParticipants in the custom-made insole group experienced statistically significant more pain during activity at 26 weeks than participants in the usual care group (overall effect 1.06; 95% CI 0.36 to 1.75). There were no significant differences between groups in other outcomes. Total societal costs in the custom-made insole group were non-significantly higher than in the usual care group (mean difference €376; 95% CI −€1775 to €2038). The intervention with custom-made insoles was dominated by usual care by the GP (ie, more expensive and less effective) for pain during activity and quality of life outcomes. For the outcome pain at rest, the intervention was more expensive and more effective than usual care. However, the maximum probability of cost-effectiveness was only 0.59 at very high ceiling ratios.ConclusionsThese findings show that that custom-made insoles are not cost-effective in comparison with GP-led usual care. Clinicians should be reserved in prescribing custom-made insoles for PHP as a primary intervention.Trial registration numberNTR5346.

Objective To determine which baseline characteristics, especially clinically variables like pain, stiffness, physical functioning and disease variables, are associated with incident hip OA within 10 years in first presenters with hip complaints. Rheumatology key messages History taking and not physical exam variables are associated with incident hip osteoarthritis. Specific questions about daily life activities are associated with incident hip OA. These questions are about pain while walking/shopping, difficulties putting socks on/off and rising from bed. Methods Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study (n = 1002). Incident hip OA was defined as fulfilling the clinical ACR criteria for hip OA, a Kellgren and Lawrence score ≥2 with hip pain, or received a hip replacement during follow-up. Baseline measurements were used of participants with hip complaints and without hip OA. Principal component analysis (PCA) was used to reduce the number of correlated variables. Associations between baseline characteristics (including PCA components) and incident hip OA were investigated using logistic regression analysis, adjusted for age, sex and BMI. Results In total, 312 participants (85% female and 98% Caucasian) were included, 181 developed hip OA. PCA resulted in four components. Incident hip OA was associated with (i) component 1 (general presence of pain and symptoms) [odds ratio (OR) = 1.46 (95%CI: 1.08, 1.98)], (ii) component 3 (relatively high levels of pain during shopping/walking combined with less difficulty with putting socks on/off and rising from bed) [OR = 1.58 (95%CI: 1.18, 2.12)] and (iii) knee pain [OR = 0.34 (95% CI: 0.17, 0.66)]. Conclusion In first presenters with hip complaints, use of a few history-taking variables might allow better recognition of those at higher odds for incident hip OA within 10 years.

Background Shoulder pain is the third most common musculoskeletal complaint in primary care. The international guidelines for general practitioners (GPs) recommend a stepwise treatment of shoulder pain. Little is known about the actual distribution of these treatments in current practice. Objective To gain insight in the incidence and current management of shoulder complaints in Dutch general practice. Methods A retrospective cohort study was conducted using a health care database containing the full electronic medical records of approximately 200 000 patients in Dutch general practice. A search algorithm was constructed to identify incident cases of shoulder complaints from January 2012 to December 2017. Data on the management of shoulder complaints were manually validated in a random sample of 1000 cases. Results The overall incidence of shoulder complaints was 30.3 (95% confidence interval 29.9–30.7) per 1000 person-years. More than half of the patients (58.6%) consulted their GP only once, 44.4% two times or more and 19.7% three times or more. For most patients (58.1%), the GP applied a wait-and-see policy or prescription of oral medication in the first consultation. However, no less than 42.9% of the patients were referred or received an injection already in the first consultation. Conclusions There is a wide variety of treatments for shoulder complaints applied by the GP. Some patients are referred or received an injection already in the first consultation. The stepwise approach recommended by the guideline, might not always be applicable due to the diversity of patient- and shoulder characteristics presented in general practice.

Diagnostic reasoning is an important topic in General Practitioners’ (GPs) vocational training. Interestingly, research has paid little attention to the content of the cases used in clinical reasoning education. Malpractice claims of diagnostic errors represent cases that impact patients and that reflect potential knowledge gaps and contextual factors. With this study, we aimed to identify and prioritize educational content from a malpractice claims database in order to improve clinical reasoning education in GP training. With input from various experts in clinical reasoning and diagnostic error, we defined five priority criteria that reflect educational relevance. Fifty unique medical conditions from a malpractice claims database were scored on those priority criteria by stakeholders in clinical reasoning education in 2021. Subsequently, we calculated the mean total priority score for each condition. Mean total priority score (min 5–max 25) for all fifty diagnoses was 17,11 with a range from 13,89 to 19,61. We identified and described the fifteen highest scoring diseases (with priority scores ranging from 18,17 to 19,61). The prioritized conditions involved complex common (e.g., cardiovascular diseases, renal insufficiency and cancer), complex rare (e.g., endocarditis, ectopic pregnancy, testicular torsion) and more straightforward common conditions (e.g., tendon rupture/injury, eye infection). The claim cases often demonstrated atypical presentations or complex contextual factors. Including those malpractice cases in GP vocational training could enrich the illness scripts of diseases that are at high risk of errors, which may reduce diagnostic error and related patient harm.

Background Anxiety problems are common in both children and adolescents, and many affected children do not receive appropriate treatment. Understaffing of mental healthcare services and long waiting lists form major barriers. In the Netherlands, practice nurses have been introduced into general practice to support general practitioners (GPs) in the management of psychosocial problems. In this study we investigated the views of GPs and practice nurses on their management of paediatric anxiety problems. Methods We performed an exploratory study using semi-structured interviews with 13 GPs and 13 practice nurses in the greater Rotterdam area in 2021. Interviews were transcribed and coded into topics, which were categorized per research question. Results In their management of paediatric anxiety problems, both GPs and practice nurses try to explore the case and the needs of affected children and their parents. GPs rarely follow up affected children themselves. They often refer the child, preferably to their practice nurse. Practice nurses regularly initiate follow-up consultations with affected children themselves. Practice nurses reported using a variety of therapeutic techniques, including elements of cognitive behavioural therapy. In more severe cases, practice nurses refer the child to external mental healthcare services. GPs reported being satisfied with their collaboration with practice nurses. Both GPs and practice nurses experience significant barriers in the management of paediatric anxiety problems. Most importantly, long waiting lists for external mental health care were reported to be a major difficulty. Improving cooperation with external mental healthcare providers was reported to be an important facilitator. Conclusions In their management of paediatric anxiety problems, GPs and practice nurses experience major challenges in the cooperation with external mental healthcare providers and in the long waiting lists for these services. GPs and practice nurses believe that thanks to their shared approach more children with anxiety problems can remain treated in general practice. Future research is needed to evaluate the treatment outcomes of the shared efforts of GPs and practice nurses in their management of paediatric anxiety problems.

Plantaire hielpijn is een veelvoorkomende voetklacht met veel impact. Er zijn verschillende interventies mogelijk, waaronder op maat gemaakte inlegzolen. Die laatste zijn duur (100-150 euro) en er is geen evidence voor. In dit gerandomiseerde gecontroleerde onderzoek met 185 deelnemers bleek dat een op maat gemaakte zool in eerste instantie geen toegevoegde waarde heeft ten opzichte van een placebozool of gebruikelijke zorg door de huisarts. Of dit ook geldt bij aanhoudende klachten of bij specifieke subgroepen is niet onderzocht.

Insufficient light exposure is assumed to be related to a wide array of health problems, though few studies focus on the role of whole-day light exposure in the habitual setting in the development of these health problems. The current review aims to describe the association between personal light exposure in the habitual setting and sleep-wake rhythm and mood in healthy adults from the general population. Five databases (Embase, Medline Epub, Web of Science, PsycINFO, and Google Scholar) were searched in June 2019. The inclusion criteria included: assessment directly of light exposure on the participants for at least one full day; reporting on both individual personal light exposure and outcomes. The quality of the papers was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung and Blood Institute. The current review followed the PRISMA guidelines. In total, 8140 papers were identified in the database search. Twenty-five papers were eventually included in this review. All included studies were cross-sectional, and individual light exposure was usually measured with a wrist-worn device. Five studies received a "good" quality rating, 16 received a "fair" rating, and the remaining 4 a "poor" quality rating. The overall quality of the included studies was considered low because of the lack of intervention studies and the fact that light exposure was measured on the wrist. Given the low quality of the included studies, the current review can only provide a first exploration on the association between light exposure and sleep-wake rhythm and mood in healthy adults from the general population. Limited evidence is presented for a positive relationship between the amount and timing of light exposure on the one hand and rest-activity rhythm and some estimates of sleep architecture on the other. The evidence on an association between light exposure and circadian phase, sleep estimates, sleep quality, and mood is conflicting. Data from intervention studies are needed to gain insight into the causal mechanism of the relationship between light exposure and sleep-wake rhythm and mood.

Background The Dutch guideline for general practitioners (GPs) advises biannual surveillance of hepatitis B (HBV) patients and referral of every hepatitis C (HCV) patient. We aimed to study the prevalence, incidence, and the management of hepatitis B and C in primary care. Methods This is a retrospective cohort study using the Rijnmond Primary Care database (RPCD), including health care data of medical records of GPs of approximately 200,000 patients in the area of Rotterdam, the Netherlands. Patient records were selected based on laboratory results, International Classification of Primary Care (ICPC) codes, and free-text words. Results In total, 977 patients were included: 717 HBV, 252 HCV, and 8 HBV/HCV coinfected patients. Between 2013 and 2019, the prevalence of HBV and HCV declined from 5.21 to 2.99/1,000 person-years (PYs) and 1.50 to 0.70/1,000 PYs, respectively. We observed that the majority of the patients had been referred to a medical specialist at least once (71% HBV and 89% HCV patients). However, among chronic patients, we observed that 36.2% of the HBV patients did not receive adequate surveillance by their GP (≥2 alanine aminotransferase checks within 3 years) or a medical specialist. In addition, 44.4% of the HCV patients had no record about successful antiviral treatment. Conclusions This study demonstrated a declining prevalence in viral hepatitis B and C in primary care in the Netherlands. However, a substantial part of the patients did not receive adequate surveillance or antiviral therapy. It is therefore crucial to involve GPs in case finding and in follow-up after treatment.

ObjectiveTo explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints.MethodsData were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features.ResultsIn total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years.ConclusionOne out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.

ObjectivesTo compare custom-made insoles to sham insoles and general practice (GP)-led usual care in terms of pain at rest and during activity at 12 weeks follow-up in individuals with plantar heel pain.MethodsIn this randomised clinical trial 185 patients aged 18 to 65 years, with a clinical diagnosis of plantar heel pain for at least 2 weeks, but no longer than 2 years were recruited. Patients were randomly allocated into three groups: (1) GP-led treatment, plus an information booklet with exercises (usual care; n=46), (2) referral to a podiatrist for treatment with a custom-made insole plus an information booklet with exercises (custom-made insole; n=70) and (3) referral to a podiatrist and treatment with a sham insole plus an information booklet with exercises (sham insole; n=69). As well as the primary outcome of pain severity (11-point Numerical Rating Scale) we used the Foot Function Index (0 to 100) as a secondary outcome.ResultsOf 185 randomised participants, 176 completed the 12-week follow-up. There was no difference in pain or function between the insole and the sham groups at 12 weeks. Participants in the GP-led usual care group reported less pain during activity at 12 weeks, (mean difference (MD) 0.94, 95% CI 0.23 to 1.65), less first step pain (MD 1.48, 95% CI 0.65 to 2.31), better function (MD 7.37, 95% CI 1.27 to 13.46) and higher recovery rates (RR 0.48, 95% CI 0.24 to 0.96) compared with participants in the custom insole group.ConclusionsReferral to a podiatrist for a custom-made insole does not lead to a better outcome compared to sham insoles or compared to GP-led usual care.Trial registration numberNTR5346.

Background: Although a large number of adults with intellectual disabilities have depressive symptoms, non-pharmacological treatments are scarce. The present authors investigated whether bright light therapy (BLT) is effective in decreasing depressive symptoms compared to care as usual. Methods: This multicentre randomized controlled trial consisted of three study groups (10,000 lux BLT, dim light BLT and a no-BLT group). Participants received BLT for 30 min in the morning (14 consecutive days), additional to their regular care. Primary outcome was as follows: depressive symptoms measured with the ADAMS Depressive Mood subscale 1 week after the end of BLT (same time period in the noBLT group). Results: Forty-one participants were included in our trial. In both BLT groups, a significant decrease in depressive symptoms was seen. No significant differences were found between 10,000 lux BLT and no-BLT (p = .199) and no significant differences between dim light BLT and no-BLT (p = .451). A minimum amount of side effects and no adverse events were reported. Conclusions: In both BLT interventions, a decrease in depressive symptoms was seen. With 10,000 lux BLT, depressive symptoms decreased even below the clinical cut-off point, which makes BLT a promising intervention for clinical practice.

Musculoskeletal (MSK) pain is frequently reported among adolescents and children and is a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year-old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population-based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6 years of age (N = 6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain, and behavioral problems were extracted from questionnaires. The body mass index SD score was calculated from objectively measured weight and height. A 3-month prevalence of 10.0% was found for MSK pain in children, of which one-third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status reported MSK pain more frequently compared to other pain and no pain. Although no associations were found between MSK pain and children's body mass index and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (odds ratio 5.10, 95% confidence interval 3.25-7.98) and behavioral problems (odds ratio 2.10, 95% confidence interval 1.19-3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral problems are independently associated with MSK pain in the studied population.

Door stijgende zorgkosten staat substitutie van zorg hoog op de politieke agenda. In dit onderzoek verkenden wij middels interviews welke opvattingen zorgverleners hebben over de verplaatsing van laagrisicohuidkankerzorg van het ziekenhuis naar de eerste lijn. Hoewel de betrokken zorgverleners over het algemeen gematigd positief waren over substitutie van huidkankerzorg, blijken substantiele barrieres een succesvolle implementatie op dit moment in de weg te staan. Maatregelen die substitutie kunnen bevorderen zijn dermato-oncologiescholing voor huisartsen en het verbeteren van de samenwerking tussen de lijnen. Huisartsen verwachten daarnaast inspanningen van dermatologen om hun vertrouwen en dat van patienten in huisartsen te verhogen, en compensatie in tijd en geld.

Objectives: To study the impact of initial healthcare for a lateral ankle sprain on the outcome of neuromuscular training (NMT) on recurrent sprains and describe athlete characteristics receiving different types of healthcare. Design: Secondary analysis of three randomized trials. Method: From three previous trials evaluating NMT, data on athlete characteristics, type of initial healthcare and a recurrent sprain during one-year follow-up were collected (N = 705). Multilevel logistic regression analyses were used to test the impact of initial healthcare on the outcome of NMT on recurrent sprains. Potential differences in athlete characteristics between different types of healthcare were examined using one-way analysis of variance and Pearson chi-square test. Results: After NMT, 39.7% of the athletes visiting paramedical care reported a recurrent sprain, 21.8% of secondary and 34.0% of primary care. Athletes who visited a physiotherapist reported more recurrent sprains, than those not visiting a physiotherapist (adjusted OR 3.15;95%CI 1.88-5.23). Athletes visiting paramedical (49.7%) and primary care (48.4%) used more braces and/or tape during sport than those not visiting any care (34.2%). Conclusions: The initial type of healthcare of athletes with an ankle sprain, that consecutively received NMT, seems to impact the occurrence of recurrent sprains. Physiotherapists may be visited by athletes with a poorer prognosis, which may be explained by different athlete characteristics.

ObjectivesIn 2016, the SKINCATCH Trial, a clustered multi-centre randomised trial, was initiated to assess whether low-risk basal cell carcinomas (BCCs) can be treated by general practitioners (GPs) without loss of quality of care. The trial intervention consisted of a tailored 2-day educational course on skin cancer management. The aim of this process evaluation was to investigate GPs’ exposure to the intervention, implementation of the intervention and experiences with the intervention and trial.Research design and methodsData on exposure to the intervention, implementation and experiences were obtained at several points during the trial. Complementary quantitative components (ie, surveys, database analysis, medical record analysis) and qualitative components (ie, interviews and focus groups) were used. Quantitative data were analysed using descriptive statistics; qualitative data were summarised (barrier interviews) or audiorecorded, transcribed verbatim and thematically analysed using Atlas.Ti (focus groups).ResultsFollowing a 100% intervention exposure, results concerning the implementation of the trial showed that aside from the low inclusion rate of patients with low-risk BCCs (n=54), even less excisions of low-risk BCCs were performed (n=40). Although the intervention was experienced as highly positive, several barriers were mentioned regarding the trial including administrative challenges, lack of time and high workload of GPs, low volume of BCC patients and patients declining to participate or requesting a referral to a dermatologist.ConclusionsAlthough GPs’ participation in the highly valued training was optimal, several barriers may have contributed to the low inclusion and excision rate of low-risk BCCs. While some of the issues were trial-related, other barriers such as low patient-volume and patients requesting referrals are applicable outside the trial setting as well. This may question the feasibility of substitution of surgical excisions of low-risks BCCs from secondary to primary care in the current Dutch setting.Trial registration numberTrial NL5631 (NTR5746).

IntroductionThe Healthy Ageing and Intellectual Disability (HA-ID) study is a prospective multicentre cohort study in the Netherlands that started in 2008, including 1050 older adults (aged ≥50) with intellectual disabilities (ID). The study is designed to learn more about the health and health risks of this group as they age. Compared with the amount of research in the general population, epidemiological research into the health of older adults with ID is still in its infancy. Longitudinal data about the health of this vulnerable and relatively unhealthy group are needed so that policy and care can be prioritised and for guiding clinical decision making about screening, prevention and treatment to improve healthy ageing.Methods and analysisThis article presents a summary of the previous findings of the HA-ID study and describes the design of the 10-year follow-up in which a wide range of health data will be collected within five research themes: (1) cardiovascular disease; (2) physical activity, fitness and musculoskeletal disorders; (3) psychological problems and psychiatric disorders; (4) nutrition and nutritional state; and (5) frailty.Ethics and disseminationEthical approval for the 10-year follow-up measurements of the HA-ID study has been obtained from the Medical Ethics Review Committee of the Erasmus MC, University Medical Centre Rotterdam (MEC-2019-0562).Trial registration numberThis cohort study is registered in the Dutch Trial Register (NTR number NL8564) and has been conducted according to the principles of the Declaration of Helsinki.

BackgroundChildren and adolescents with overweight are known to have lower Quality of Life (QoL) compared to peers with a normal weight. QoL is a broad concept and is associated with many factors. A better understanding of the factors associated with QoL in children and adolescents and their impact on the association between overweight/obesity and QoL, may help to develop and improve interventions that lead to an improvement in QoL in children/adolescents with a high body mass index (BMI > 25). This study investigated the possible mediating effects of somatic complaints and general practitioner consultations in the association between overweight/obesity and QoL in children and adolescents.MethodsFor the current study, cross-sectional data were used from a longitudinal study, the DOERAK cohort, collected from general practitioners’ medical files and through questionnaires.This cohort included 2-18 year olds with normal weight and overweight. Uni- and multivariate regression analyses were performed to gain more insight into variables associated with QoL. Mediation analyses were performed to investigate the possible mediating effects of somatic complaints and GP consultations in the association between overweight/obesity and QoL in children.ResultsIn the total sample of 733 participants aged 2-18 years, participants with normal weight had a significantly higher QoL (83.64, SD10.65) compared to participants with overweight (78.61, SD14.34) and obesity (76.90, SD13.63) at baseline. The multivariate analyses showed that a lower socio-economic status (SES), higher BMIz, and the presence of somatic complaints are associated with a lower QoL. The mediation analysis showed a significant effect of the indirect pathway of BMIz on QoL through somatic complaints (β = − 0.46, 95% CI[− 0.90, − 0.06]).ConclusionBMIz has a direct impact on QoL in children and adolescents. Somatic complaints seem to mediate the effect of BMIz on QoL.

Background Depressive symptoms and stress are common in adults with intellectual disabilities. Our aim was to explore long‐term biological stress levels, assessed by hair cortisol (HairF) and cortisone (HairE) concentrations, in adults with intellectual disabilities and depressive symptoms and to investigate the effects of bright light therapy (BLT) on hair glucocorticoids. Method Scalp hair samples (n = 14) were retrospectively examined at baseline and post‐BLT (10.000 and 300 lux). Liquid chromatography–tandem mass spectrometry was used to measure hair glucocorticoids. Results A significant correlation was found between baseline HairF and depression scores (r = .605, p = .028). Post‐intervention HairE levels were significantly increased ([95% CI: 11.2–17.4 pg/mg], p = .003), in particular after dim light (300 lux) ([95% CI: 10.0–18.3 pg/mg], p = .020). Conclusions This study showed that retrospectively examining biological levels of stress in adults with intellectual disabilities seems a potentially promising and objective method to gain insight in the stress level of adults with intellectual disabilities.

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. Methods and findings On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19–specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. Conclusions In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences., Marije J. Splinter and colleagues assess the prevalence of healthcare avoidance during the COIVD-19 pandemic and investigate related determinants, Author summary Why was this study done? ➢ During the Coronavirus Disease 2019 (COVID-19) pandemic, consultation rates in both primary and specialist care declined compared to prepandemic levels, which can partially be attributed to the postponement or cancellation of elective and nonurgent medical care. ➢ It is unclear to what extent these declines in consultation rates could be related to healthcare avoidance by patients in the general population. ➢ To evaluate the collateral health damage of the COVID-19 pandemic, it is important to not only assess the prevalence of healthcare avoidance, but also for what symptoms healthcare was avoided and which determinants are associated with this behaviour. What did the researchers do and find? ➢ We sent out a paper questionnaire to 8,732 participants of the population-based Rotterdam Study containing several COVID-19–related subjects, such as healthcare utilisation, work status, mental and physical health, and concerns about contracting COVID-19. ➢ About 6,241 participants (73%) returned the questionnaire, of whom 5,656 participants (90.6%) were included in our analyses. We found that 1,142 of them (20.2%) avoided healthcare during the COVID-19 pandemic, often for symptoms that might have needed urgent medical evaluation, such as limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). ➢ Determinants that were most strongly associated with healthcare avoidance were female sex, poor self-appreciated health, and high levels of depression and anxiety. What do these findings mean? ➢ The results of this population-based study suggest that healthcare avoidance contributed to the decline in consultation rates during the COVID-19 pandemic. Importantly, our findings suggest that this behaviour may be associated with certain vulnerable groups within the population. ➢ These findings should be interpreted in light of the limitations of this study, which include that the actual severity of the symptoms that were reported by participants is unknown, since they were not medically evaluated when they experienced these symptoms. ➢ The findings of this study can be used to develop policy interventions targeted to vulnerable individuals who may be more likely to exhibit healthcare avoiding behaviours.

Background Guidelines for shoulder pain in general practice recommend treatment with corticosteroid injections (CSI) if initial pain management fails. However, little is known about the actual use and safety of CSIs in treatment by general practitioners (GP). Objective The objective of this study was to gain insight into the use and safety of CSIs for patients with a new episode of shoulder pain in general practice. Methods A retrospective cohort study was conducted using a healthcare database containing the electronic medical records of approximately 200,000 patients in general practice. A search algorithm was constructed to identify patients with a new episode of shoulder pain between January 2012 and December 2017. Data on the use of CSIs in 2 random samples (n = 1,000) were manually validated for a 12-month period after the diagnosis. Results In total, 26% of the patients with a new episode of shoulder pain received a CSI. The patient’s age (OR 1.03, 95% CI 1.02–1.04) and a history of shoulder pain (OR 1.52, 95% CI 1.13–2.12) were significantly associated with the administration of a CSI. Half of the patients received the CSI in the first consultation. The patient’s age was positively associated with the likelihood of receiving the CSI in the first consultation (OR 1.01, 95% CI 1.00–1.02). No serious adverse reactions were recorded by the GP. Conclusion In contrast to the guidelines, CSIs were frequently administered in the first consultation. Older patients and patients with a history of shoulder pain were more likely to receive a CSI for shoulder pain.

BackgroundVitamin tests are increasingly ordered by GPs, but a clinical and evidence-based indication is often lacking. Harnessing technology (that is, decision support tools and redesigning request forms) have been shown to reduce vitamin requests.AimTo investigate whether the number of vitamin tests may be reduced by providing a multi-level intervention programme based on training, monitoring, and feedback.Design & settingThis was a cluster randomised intervention study performed in 26 primary care health centres (>195 000 patients) in the Netherlands. The relative reduction in ordered vitamin D and B12 tests was determined after introduction of two de-implementation strategies (1 May 2017 to 30 April 2018).MethodHealth centres randomised to de-implementation strategy 1 received education and benchmarking of their own vitamin test ordering behaviour every 3 months. Health centres in de-implementation strategy 2 received the same education and benchmarking, but supplemented with educational material for patients.ResultsThe number of vitamin D tests decreased by 23% compared to the 1-year pre-intervention period (1 May 2016 to 30 April 2017). For vitamin B12 tests an overall reduction of 20% was found. Provision of patient educational information showed additional value over training and benchmarking of GPs alone for vitamin D test ordering (10% extra reduction, odds ratio [OR] 0.88, 95% confidence interval [CI] = 0.83 to 0.92), but not for vitamin B12 ordering (4% extra reduction, OR 0.96, 95% CI = 0.91 to 1.02). Nationwide, this would result in over €3 200 000 in savings on healthcare expenditure a year.ConclusionA structured intervention programme, including training and benchmarking of GPs regarding their diagnostic test ordering, resulted in a significant reduction in ordered vitamin tests. Additional information provision to patients resulted in a small but still relevant additional reduction. If implemented on a national level, a substantial cost saving could be achieved.

Background: It remains unclear to what extent patients with traumatic knee complaints aged 18–45 years seen in general practice experience difficulties with return to sports. Objectives: This study aims to determine the proportion of patients with a knee trauma that return to sports at six weeks and three months follow-up. Also examined were associations between no return to sports and baseline patient/trauma characteristics, knee complaints and MR (magnetic resonance) findings, as well as the additive value of MR findings. Methods: Included were patients with traumatic knee complaints participating in a randomized controlled trial assessing the cost-effectiveness of an MR scan in general practice. Patients were classified as ‘no return to sports’ or ‘return to sports’ (sports on pre-injury or adapted level). Potential baseline predictors for no return to sports were assessed using logistic regression analyses. The area under the curves (AUC) was compared. Results: At six weeks and three months follow-up, 147 (59%) and 175 (74%) patients, respectively, reported return to sports. Combining patient characteristics, trauma characteristics and knee complaints predicted no return to sports with an AUC of 0.86 (95%CI: 0.81–0.90) at six weeks and of 0.82 (95%CI: 0.76–0.88) at three months follow-up. After adding MR findings, the AUC was 0.79 (95%CI: 0.71–0.87) at six weeks and 0.79 (95%CI: 0.70–0.88) at three months follow-up. Conclusion: Three out of four patients with a knee trauma in general practice reported return to sports at three months follow-up. A combination of patient/trauma characteristics and knee complaints predicted no return to sports, whereas MR findings had no additive value. Trial registration: Dutch trial registration: registration number: NTR3689. registration date: 7 November 2012.

Inleiding Verschillende internationale richtlijnen adviseren een intra-articulaire corticosteroidinjectie bij pijnlijke heupartrose, maar de systemische werking van corticosteroiden bij heupartrose is onbekend. Wij onderzochten of intramusculaire corticosteroidinjecties de pijn kunnen verminderen en vergeleken deze met placebo-injecties. Methode In deze gerandomiseerde dubbelblinde RCT kregen patienten met pijnlijke heupartrose een intramusculaire injectie met ofwel 40 mg triamcinolonacetonide ofwel placebo. Primaire uitkomstmaat was de heuppijn in rust en tijdens lopen twee weken na de injectie, gemeten op een visuele analoge pijnschaal en op de WOMAC-pijnindex. Secundaire uitkomstmaten waren de pijnscores op vier, zes en twaalf weken en de overige WOMAC-scores. Gegevens werden geanalyseerd met linear mixed models. Resultaten In totaal werden 106 patienten geanalyseerd, 52 in de corticosteroidgroep en 54 in de placebogroep. In de corticosteroidgroep zagen we twee weken na de injectie een signifcant en klinisch relevant verschil ten opzichte van placebo op de pijn in rust (extra pijnvermindering –1,3; 95%-BI –2,3 tot –0,3). Dit efect bleef tot twaalf weken na de injectie aanwezig. Na vier, zes en twaalf weken zagen we ook een signifcant verschil voor pijn tijdens lopen, en na zes en twaalf weken scoorde de interventiegroep ook beter op de WOMAC-pijnschaal. Conclusie Een intramusculaire corticosteroidinjectie bij heupartrose vermindert de pijn in rust na twee tot twaalf weken beter dan placebo. Respectievelijk vier tot twaalf en zes tot twaalf weken na de injectie zijn ook de pijn bij lopen en de score op de WOMAC-pijnschaal beter dan bij placebo.

BackgroundPlantar heel pain (PHP) is a common cause of foot complaints in general practice. However, information on the occurrence and practical management is scarce.AimThe aim of this study was to determine the incidence and prevalence of PHP in Dutch primary care and to gain insight into the types of treatments provided to patients with PHP in primary care.Design and settingA cohort study was conducted using a healthcare database containing the electronic general practice medical records of approximately 1.9 million patients throughout the Netherlands.MethodA search algorithm was defined and used to identify cases of PHP from January 2013 to December 2016. Descriptive statistics were used to obtain the incidence and prevalence. Data on the management of PHP were manually validated in a random sample of 1000 patients.ResultsThe overall incidence of PHP was 3.83 cases (95% confidence interval [CI] = 3.77 to 3.89) per 1000 patient-years, the incidence in females was 4.64 (95% CI = 4.55 to 4.72), and 2.98 (95% CI = 2.91 to 3.05) in males. The overall prevalence of PHP was 0.4374% (95% CI = 0.4369 to 0.4378%). Incidence of PHP peaked in September and October of each calendar year. The most commonly applied strategies were a wait-and-see policy (18.0%, n = 168), use of non-steroidal anti-inflammatory drugs (NSAIDs) (19.9%, n = 186), referral to a paramedical podiatric specialist (19.7%, n = 184), and advice to wear insoles (16.4%, n = 153). Treatment strategies varied greatly among GPs.ConclusionThere was large variation in treatment strategies of GPs for patients with PHP. GPs should be aware of conflicting evidence for interventions, such as insoles, and focus more on exercises for which there is evidence for effectiveness.

Objectives To examine clinical and radiological characteristics of participants with an ankle sprain in general practice, classified into subgroups of a previously described chronic ankle instability (CAI) model. Design Cross-sectional study. Methods 206 participants, who visited their general practitioner with a lateral ankle sprain 6–12 months before inclusion, completed a questionnaire, physical examination, radiography and magnetic resonance imaging. They were classified into three subgroups of the previously described CAI-model: mechanical instability (MI), perceived instability (PI) and recurrent sprains (RS). Regression analyses were applied to evaluate differences in subgroup characteristics. Results A total of 192 participants were eligible to be classified into the model. Of these participants, 153 participants were classified into the subgroups and 39 could not be classified. With overlap between the subgroups and patients falling into more than one subgroup, 59 were classified having MI, 145 having PI and 30 having RS. Participants with RS and PI were more often sports participants (OR 6.83;95%CI 1.35–34.56 and OR 4.44;95%CI1.06–18.63 respectively) than participants without RS and PI. Participants with MI more often had a tenderness on palpation of the anterior talofibular ligament (OR 4.09;95%CI 1.91–8.72) and a KL-score ≥ 1 in the talonavicular joint on X-ray (OR 2.24;95%CI 1.09–4.58), compared to participants without MI. Conclusions Sports participation, tenderness on palpation of the anterior talofibular ligament and early signs of osteoarthritis were variables that discriminated between subgroups of CAI. However, further research is mandatory in order to examine the usefulness of the CAI model in relation to prognosis and suitable intervention.