The development of an ICF-based questionnaire for patients with chronic conditions in primary care.

OBJECTIVES: We developed a self-reported questionnaire for patients in primary care with chronic conditions aged 50 years or older. The questionnaire supports a more person-centered approach by adopting a biopsychosocial focus on functional status instead of a focus on disease. STUDY DESIGN AND SETTING: Based on the International Classification of Functioning, Disability and Health (ICF), an ICF Primary Care set for patients with chronic conditions was constructed in three phases. In the first phase, we identified relevant ICF categories for the ICF Primary Care set by using existing ICF sets for chronic health conditions. The ICF Primary Care set was completed by a multidisciplinary expert panel and consisted of 52 ICF categories covering ICF's body functions, activities, participation, environmental factors, and personal factors. In the last phase, we constructed a draft version of the questionnaire by converting the ICF categories from the ICF Primary Care set into questions and corresponding scales. To improve the draft version of the questionnaire, we conducted cognitive interviews with patients with chronic conditions in an iterative process, focusing on the problems patients experienced in answering the items of the questionnaire. Interview analysis was used for assessing the content and construct validity of the questionnaire. RESULTS: Thirty cognitive interviews with patients were conducted in five different interview rounds. In these interviews, we identified 124 problems in the responding process of answering the questionnaire, mostly concerning difficulties with the comprehension of the constructs of the questions. The number of problems reduced from an average of 11 problems per interview in the first round to an average of two problems in the last round. CONCLUSION: Conclusion: The final version of the questionnaire demonstrated high content and construct validity (i.e., patients are well capable of describing their functional status in terms of ICF) and is applicable in primary care in the Netherlands.

Do practice characteristics explain differences in morbidity estimates between electronic health record based general practice registration networks?

BACKGROUND: General practice based registration networks (GPRNs) provide information on population health derived from electronic health records (EHR). Morbidity estimates from different GPRNs reveal considerable, unexplained differences. Previous research showed that population characteristics could not explain this variation. In this study we investigate the influence of practice characteristics on the variation in incidence and prevalence figures between general practices and between GPRNs. METHODS: We analyzed the influence of eight practice characteristics, such as type of practice, percentage female general practitioners, and employment of a practice nurse, on the variation in morbidity estimates of twelve diseases between six Dutch GPRNs. We used multilevel logistic regression analysis and expressed the variation between practices and GPRNs in median odds ratios (MOR). Furthermore, we analyzed the influence of type of EHR software package and province within one large national GPRN. RESULTS: Hardly any practice characteristic showed an effect on morbidity estimates. Adjusting for the practice characteristics did also not alter the variation between practices or between GPRNs, as MORs remained stable. The EHR software package 'Medicom' and the province 'Groningen' showed significant effects on the prevalence figures of several diseases, but this hardly diminished the variation between practices. CONCLUSION: Practice characteristics do not explain the differences in morbidity estimates between GPRNs.

Neurological and psychiatric tolerability of rilpivirine (TMC278) vs. efavirenz in treatment-naïve, HIV-1-infected patients at 48 weeks.

OBJECTIVES: The aim of the study was to compare the neuropsychiatric safety and tolerability of rilpivirine (TMC278) vs. efavirenz in a preplanned pooled analysis of data from the ECHO and THRIVE studies which compared the safety and efficacy of the two drugs in HIV-1 infected treatment naïve adults. METHODS: ECHO and THRIVE were randomized, double-blind, double-dummy, 96-week, international, phase 3 trials comparing the efficacy, safety and tolerability of rilpivirine 25 mg vs. efavirenz 600 mg once daily in combination with two background nucleoside/tide reverse transcriptase inhibitors. Safety and tolerability analyses were conducted when all patients had received at least 48 weeks of treatment or discontinued earlier. Differences between treatments in the incidence of neurological and psychiatric adverse events (AEs) of interest were assessed in preplanned statistical analyses using Fisher's exact test. RESULTS: At the time of the week 48 analysis, the cumulative incidences in the rilpivirine vs. efavirenz groups of any grade 2-4 treatment-related AEs and of discontinuation because of AEs were 16% vs. 31% (P<0.0001) and 3% vs. 8% (P=0.0005), respectively. The incidence of treatment-related neuropsychiatric AEs was 27% vs. 48%, respectively (P<0.0001). The incidence of treatment-related neurological AEs of interest was 17% vs. 38% (P<0.0001), and that of treatment-related psychiatric AEs of interest was 15% vs. 23% (P=0.0002). Dizziness and abnormal dreams/nightmares occurred significantly less frequently with rilpivirine vs. efavirenz (P<0.01). In both groups, patients with prior neuropsychiatric history tended to report more neuropsychiatric AEs but rates remained lower for rilpivirine than for efavirenz. CONCLUSIONS: Rilpivirine was associated with fewer neurological and psychiatric AEs of interest than efavirenz over 48 weeks in treatment-naïve, HIV-1-infected adults.

Effect of gender and race on the week 48 findings in treatment-naïve, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE.

OBJECTIVES: A week 48 efficacy and safety analysis with respect to gender and race was conducted using pooled data from the phase III, double-blind, double-dummy efficacy comparison in treatment-naïve, HIV-infected subjects of TMC278 and efavirenz (ECHO) and TMC278 against HIV, in a once-daily regimen versus efavirenz (THRIVE) trials. METHODS: Treatment-naïve, HIV-1-infected adults were randomized to receive rilpivirine (RPV; TMC278) 25 mg once a day (qd), or efavirenz (EFV) 600 mg qd, plus tenofovir/emtricitabine (ECHO) or tenofovir/emtricitabine, zidovudine/lamivudine or abacavir/lamivudine (THRIVE). RESULTS: A total of 1368 participants (76% male and 61% White, of those with available race data) were randomized and treated. No gender-related differences in response rate (percentage of patients with HIV-1 viral load < 50 HIV-1 RNA copies/mL, using an intent-to-treat, time-to-loss-of-virological-response algorithm) were observed (RPV: men, 85%; women, 83%; EFV: men, 82%; women, 83%). Response rates were lower in Black compared with Asian and White participants (RPV: 75% vs. 95% and 85%, respectively; EFV: 74% vs. 93% and 83%, respectively); this finding was mostly a result of higher discontinuation and virological failure rates in Black patients. Safety findings were generally similar across race and gender subgroups. However, nausea occurred more commonly in women than in men in both treatment groups. In men, diarrhoea was more frequent in the EFV group, and abnormal dreams/nightmares were more frequent in men in both the EFV and RPV groups. CONCLUSIONS: Overall response rates were high for both RPV and EFV. No gender differences were observed. However, response rates were lower among Black patients, regardless of treatment group. Gender appeared to influence the incidence of gastrointestinal adverse events and abnormal dreams/nightmares for both treatments.

The influence of population characteristics on variation in general practice based morbidity estimations.

BACKGROUND: General practice based registration networks (GPRNs) provide information on morbidity rates in the population. Morbidity rate estimates from different GPRNs, however, reveal considerable, unexplained differences. We studied the range and variation in morbidity estimates, as well as the extent to which the differences in morbidity rates between general practices and networks change if socio-demographic characteristics of the listed patient populations are taken into account. METHODS: The variation in incidence and prevalence rates of thirteen diseases among six Dutch GPRNs and the influence of age, gender, socio economic status (SES), urbanization level, and ethnicity are analyzed using multilevel logistic regression analysis. Results are expressed in median odds ratios (MOR). RESULTS: We observed large differences in morbidity rate estimates both on the level of general practices as on the level of networks. The differences in SES, urbanization level and ethnicity distribution among the networks' practice populations are substantial. The variation in morbidity rate estimates among networks did not decrease after adjusting for these socio-demographic characteristics. CONCLUSION: Socio-demographic characteristics of populations do not explain the differences in morbidity estimations among GPRNs.

The Belgian-Flemish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Belgian-Flemish language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Belgian-Flemish CHAQ was fully validated with 3 forward and 3 backward translations, while the Belgian-Flemish CHQ was equal to the Dutch version and revalidated in this study. The French version of both CHAQ and CHQ was exactly the same as the one used in France. A total of 199 subjects were enrolled: 53 patients with JIA (11% systemic onset, 40% polyarticular onset, 13% extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and 146 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular onset, and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Belgian-Flemish version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

[Immune deficiencies: diagnosis, management, some perspectives]. / Déficits immunitaires primaires: diagnostic, prise en charge, quelques perspectives.

Severe primary immunodeficiencies (PID) are rare; their global incidence is comparable to that of childhood leukemia; they include more than 100 different entities. Clinical manifestations are: unusually severe or frequent infections or infections that do not respond to adequate treatment; an increased risk of certain malignancies; sometimes auto-immune manifestations. Delayed diagnosis and management of PID can lead to severe and irreversible complications or to death. PID can become manifest only in the adult; in common variable immune deficiency, the median age at diagnosis is between the 2nd and the 3rd decade of life. PID are often transmitted genetically; recent progresses in molecular biology have allowed more precise and earlier, including antenatal, diagnosis. Molecular treatment of 3 infants with a severe immunodeficiency has recently been achieved in April 2000. Those progresses were mostly based on the study of immunodeficiency databases. We present here the work of a Belgian group specialized in PID; meetings have started in June 1997. This group establishes guidelines for the diagnosis and treatment of PID, adapted to the local situation. The elaboration of a national register of PID is also underway; this has to provide all guaranties of anonymity to patients and families. Such a register already exists at the European level; it has provided the basis for new diagnostic and therapeutic possibilities. The inclusion of Belgian data in this register should allow essential progresses essential for our patients.

Progressive pseudorheumatoid dysplasia.

A rare case of progressive pseudorheumatoid dysplasia (PPD) in a 9-year-old girl is presented. Clinically, chronic painless swollen joints, accompanied by progressive motion restriction and progressive walking difficulties, were found. Radiologically, there was enlargement of the epimetaphyseal portions of the large joints, metacarpal heads, and phalanges, and generalized platyspondyly with irregular delineation of the endplates of the vertebral bodies. The radioclinical features at the peripheral joints were originally misdiagnosed as juvenile rheumatoid arthritis (JRA), and the structural spinal abnormalities were neglected and interpreted as Scheuermann's disease. However, the absence of active inflammatory parameters argues against JRA, whereas the low age of onset of the irregularities at the vertebral endplates is an argument against the diagnosis of Scheuermann's disease. The combination of the dysplastic abnormalities of the spine, with platyspondyly and Scheuermann-like lesions at an unusually low age of onset, and radiological features mimicking JRA of the peripheral joints, is the clue to the diagnosis of this rare autosomal-recessive disease. This case is the first to document the MRI features of PPD of the spine.

Cerebral complications of murine monoclonal CD3 antibody (OKT3): CT and MR findings.

Treatment of acute renal allograft rejection with mouse monoclonal antibody (OKT3) is associated with systemic and neurologic side effects. We describe cerebral abnormalities in a 13-year-old boy with steroid-resistant renal allograft rejection. After treatment with OKT3, an acute neurologic syndrome developed, including seizures, lethargy, and decreased mental function. CT and MR imaging revealed confluent cerebral lesions at the corticomedullary junction. Contrast-enhanced MR images showed patchy enhancement, indicating blood-brain barrier dysfunction. The diagnosis of OKT3-induced encephalopathy with cerebral edema and capillary leak syndrome was made. Although CT and MR findings are nonspecific, neuroradiologists should be aware of this condition in transplant patients treated with OKT3.

Defensive testing in Dutch family practice. Is the grass greener on the other side of the ocean?

BACKGROUND: Ordering laboratory tests and diagnostic imaging can be part of the defensive behavior of the physician. How often does this occur in family practice in the Netherlands? Defensive behavior is defined as a clear deviation from the family physician's usual behavior and from what is considered to be good practice in order to prevent complaints or criticism by the patient or the patient's family. METHODS: Over a 1-year period, 1989-1990, 16 family physicians in 11 practices with 31,343 patients recorded all episodes of care involving an order for laboratory tests or diagnostic imaging or both (n = 8897). The physicians selected one or more reasons to order each test from a fixed list of clinical considerations. In addition, they recorded whether they acted defensively for every test order. RESULTS: The participating physicians reported that some degree of defensive medicine was associated with 27% of all test orders. Defensive testing varied with the clinical reasons to order a test: the wish to exclude a disease or to reassure the patient was a much stronger motive for defensive testing than the intention to confirm a diagnosis or to screen. Defensive tests generally resulted in fewer abnormal findings. CONCLUSIONS: Defensive testing is an important phenomenon in Dutch family practice: it forms a well-defined element of practice despite the variations implicit in the different clinical reasons to order a test. Defensive testing is associated with a lower probability of finding an abnormal test result. The analysis of family physicians' clinical reasons for ordering tests becomes more meaningful when defensive testing is included.

A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family.

A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Anti-glomerular basement membrane glomerulopathy in a young child.

We report the youngest patient with anti-glomerular basement membrane disease described in the literature to date. Age-dependent expression of the target antigen in this auto-immune disease explains the low incidence in young children. Despite adequate immunosuppression, renal function did not recover in our patient.

Tubulo-interstitial nephritis-uveitis (TINU)-syndrome with posterior uveitis.

A case of TINU-syndrome with complications in the posterior segment is reported. A 15-year old boy presented, eight months after an acute tubulo-interstitial nephritis, a bilateral anterior uveitis, followed by an unilateral posterior uveitis with papillitis. The treatment with oral and topical corticosteroids was successful.

Atypical Kawasaki disease: an often missed diagnosis.

We describe four patients with vasculitis of the coronary and other medium sized arteries. Three of them died as a consequence of cardiac failure and the fourth had a ruptured aneurysm of the left common iliac artery. Coronary vasculitis is pathognomonic for Kawasaki disease (KD), but our patients had few other signs of this disorder, suggesting so called atypical KD. Because the described patients lacked most of the clinical criteria, the diagnosis was delayed. We focus on other clinical features in these patients and stress the importance of early recognition and treatment.

[Systemic juvenile chronic arthritis]. / Systemische juveniele chronische arthritis.

Juvenile chronic arthritis, systemic onset, is a form of juvenile chronic arthritis with severe systemic and constitutional involvement. We discuss the clinical findings, therapy and outcome of a series of forty patients we have seen in our hospital from 1979-1991.

Idiopathic arterial calcification of infancy.

We describe two twin sisters in whom calcification of different arteries was detected in the first weeks of life. Transient renal insufficiency, arterial hypertension, and skeletal abnormalities were also observed. One child had anasarca and heart decompensation at birth. Prenatal infarction of one kidney had occurred in the same infant. A kidney biopsy showed calcium deposits in all the layers of the arteries. Most findings in these patients are compatible with idiopathic arterial calcification of infancy (IACI). Investigation of calcium and phosphorus metabolism revealed spontaneously receding hypercalciuria, increased intraerythrocytic calcium levels, and transient X-ray abnormalities of the long bones. Treatment initially consisted of biphosphonate and later, the calcium antagonist flunarizin. A progressive diminution of the arterial calcification was observed in the course of both treatments.

Bronchogenic cysts in children.

Three children with symptomatic bronchogenic cysts are presented. Because of the variability in clinical presentation and the shortcomings of diagnostic procedures, bronchogenic cysts present a diagnostical problem. In view of the risk of serious complications an aggressive attitude towards all congenital cystic lung lesions is advised, even when they are asymptomatic. Surgical excision assures an excellent outcome in most cases, and is therefore the treatment of choice.

Abdominal colic due to ureteric diverticulum with stone formation.

In a 15-year-old boy right lower abdominal colicky pain was caused by intermittent obstruction of the ureter by stones which had accumulated in a ureteric diverticulum. As was shown by repeated X-rays, each of these stones had moved to the ureter and back to the diverticulum. Ureteric diverticulum mostly remains asymptomatic in children: stone formation and obstruction of the ureter by the stones is one of the instances which may cause symptoms.