Complex interventions for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, healthcare providers and/or the structure of health care are often combined (complex interventions). OBJECTIVES: To assess the effectiveness of complex interventions in the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of health care. SEARCH METHODS: For the second update we searched the Cochrane Wounds Group Specialised Register (searched 22 May 2015), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 4), The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library 2015, Issue 4), The Health Technology Assessment Database (HTA) (The Cochrane Library 2015, Issue 4), The NHS Economic Evaluation Database (NHS EED) (The Cochrane Library 2015, Issue 4), Ovid MEDLINE (1946 to 22 May 2015), Ovid MEDLINE (In-Process & Other Non-Indexed Citations 21 May, 2015), Ovid EMBASE (1974 to 21 May, 2015) and EBSCO CINAHL (1982 to 22 May, 2015). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions. DATA COLLECTION AND ANALYSIS: Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria. MAIN RESULTS: Only six RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education-centred complex intervention with usual care or written instructions, only little evidence of benefit was found. Three studies compared the effect of more intensive and comprehensive complex interventions with usual care. One study found a significant and cost-effective reduction, one of lower extremity amputations (RR 0.30, 95% CI 0.31 to 0.71). One other study found a significant reduction of both amputation and foot ulcers. The last study reported improvement of patients' self care behaviour. All six included RCTs were at high risk of bias, with hardly any of the predefined quality assessment criteria met. AUTHORS' CONCLUSIONS: There is no high-quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.

The inflammatory milieu and the insulin like growth factor axis in children with inflammatory bowel disease following recombinant human growth hormone treatment.

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1ß was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD.

Patient education for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can result in loss of limbs and even death, is one of the major health problems for people with diabetes mellitus. OBJECTIVES: To assess the effects of patient education on the prevention of foot ulcers in patients with diabetes mellitus. SEARCH METHODS: We searched The Cochrane Wounds Group Specialised Register (searched 03 September 2014); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 8). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) that evaluated educational programmes for preventing foot ulcers in people with diabetes mellitus. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook data extraction and assessment of risk of bias. Primary end points were foot ulceration or ulcer recurrence and amputation. MAIN RESULTS: Of the 12 RCTs included, the effect of patient education on primary end points was reported in only five. Pooling of outcome data was precluded by marked, mainly clinical, heterogeneity. One of the RCTs showed reduced incidence of foot ulceration (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.14 to 0.66) and amputation (RR 0.33, 95% CI 0.15 to 0.76) during one-year follow-up of diabetes patients at high risk of foot ulceration after a one-hour group education session. However, one similar study, with lower risk of bias, did not confirm this finding (RR amputation 0.98, 95% CI 0.41 to 2.34; RR ulceration 1.00, 95% CI 0.70 to 1.44). Three other studies, also did not demonstrate any effect of education on the primary end points, but were most likely underpowered. Patients' foot care knowledge was improved in the short term in five of eight RCTs in which this outcome was assessed, as was patients' self-reported self-care behaviour in the short term in seven of nine RCTs. Callus, nail problems and fungal infections improved in only one of five RCTs. Only one of the included RCTs was at low risk of bias. AUTHORS' CONCLUSIONS: In some trials, foot care knowledge and self reported patient behaviour seem to be positively influenced by education in the short term. Yet, based on the only two sufficiently powered studies reporting the effect of patient education on primary end points, we conclude that there is insufficient robust evidence that limited patient education alone is effective in achieving clinically relevant reductions in ulcer and amputation incidence.

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease.

BACKGROUND: It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). AIMS: To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. DESIGN AND SETTING: Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. INTERVENTION: Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. MAIN OUTCOME MEASURE: Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. RESULTS: Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. CONCLUSIONS: Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.

OBJECTIVE: In children with congenital hyperinsulinism (CHI), K(ATP) channel genes (ABCC8 and KCNJ11) can be screened rapidly for potential pathogenic mutations. We aimed to assess the contribution of rapid genetic testing to the clinical management of CHI. DESIGN: Follow-up observational study at two CHI referral hospitals. METHODS: Clinical outcomes such as subtotal pancreatectomy, (18)F-Dopa positron emission tomography-computed tomography (PET-CT) scanning, stability on medical treatment and remission were assessed in a cohort of 101 children with CHI. RESULTS: In total, 32 (32%) children had pathogenic mutations in K(ATP) channel genes (27 in ABCC8 and five in KCNJ11), of which 11 (34%) were novel. In those negative at initial screening, other mutations (GLUD1, GCK, and HNF4A) were identified in three children. Those with homozygous/compound heterozygous ABCC8/KCNJ11 mutations were more likely to require a subtotal pancreatectomy CHI (7/10, 70%). Those with paternal heterozygous mutations were investigated with (18)F-Dopa PET-CT scanning and 7/13 (54%) had a focal lesionectomy, whereas four (31%) required subtotal pancreatectomy for diffuse CHI. Those with maternal heterozygous mutations were most likely to achieve remission (5/5, 100%). In 66 with no identified mutation, 43 (65%) achieved remission, 22 (33%) were stable on medical treatment and only one child required a subtotal pancreatectomy. CONCLUSIONS: Rapid genetic analysis is important in the management pathway of CHI; it provides aetiological confirmation of the diagnosis, indicates the likely need for a subtotal pancreatectomy and identifies those who require (18)F-Dopa PET-CT scanning. In the absence of a mutation, reassurance of a favourable outcome can be given early in the course of CHI.

Thyroid function at diagnosis of type I diabetes.

BACKGROUND: National guidelines recommend that thyroid function is assessed at diagnosis of type I diabetes (TIDM) and annually thereafter. This paper reports an audit of thyroid surveillance in accordance with this guideline. PATIENTS: 110 patients (66 males), median age 11.3 (1.2-15.7) years at diagnosis of TIDM, were monitored for 2.3 (0.7-4.2) years. RESULTS: 21/110 (19.0%) patients had abnormal thyroid function at diagnosis of TIDM. Of these, 16 had normal thyroid function on reassessment after 45 (3-540) days. Abnormalities of thyroid function occurred more commonly in children with diabetic ketoacidosis (DKA) than those who did not have DKA (9/29, 31.0% vs 12/81, 14.8%, p<0.025). At the end of the observation period, five (4.5%) patients had minor abnormalities of thyroid function not requiring treatment and three (2.7%) were treated. CONCLUSIONS: Transient abnormalities of thyroid function are common at diagnosis of TIDM, and therefore, thyroid hormones should not be measured at this time.

Growth monitoring still has a place in selected populations of children.

In 1998, a multiprofessional group developed a consensus on growth monitoring in the UK. While routine serial measurements were not recommended in healthy children, it is clear that there is a subset of children at increased risk of growth-modifying disease who may benefit from growth monitoring. This subset includes children with genetic disorders at increased risk of thyroid dysfunction. Symptoms and signs of thyroid dysfunction are non-specific in the early stages of disease and are easily mistaken for features of an underlying genetic disorder. In this article, we report the case of a 2.8-year-old girl with 18q deletion syndrome who was profoundly weak, hypotonic and poorly responsive at diagnosis of Grave's disease. She was tall and her bone age was 2 years advanced, indicating long-standing disease. Growth monitoring of this patient should have enabled earlier diagnosis and avoided a serious and potentially fatal episode.

Patient education for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can result in loss of limbs and even death, is one of the major health problems for people with diabetes mellitus. OBJECTIVES: To assess the effects of patient education on the prevention of foot ulcers in patients with diabetes mellitus. SEARCH STRATEGY: Eligible studies were identified by searching the Cochrane Wounds Group Specialised Register (22 December 2009), the Cochrane Central Register of Controlled Trials (Cochrane Library 2009 Issue 4 ), Ovid MEDLINE (1950 to November Week 3 2009), Ovid MEDLINE In-Process & Other Non-Indexed Citations (Searched 22/12/09), Ovid EMBASE (1980 to 2009 Week 51) and EBSCO CINAHL (1982 to December 22 2009). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which evaluated educational programmes for preventing foot ulcers in people with diabetes mellitus. There was no restriction on language of the publications. DATA COLLECTION AND ANALYSIS: Two review authors independently undertook data extraction and assessment of risk of bias. Primary end-points were foot ulceration or ulcer recurrence and amputation. MAIN RESULTS: Eleven RCTs were included. Three studies described the effect of foot care education as part of general diabetes education compared with usual care. Two studies examined the effect of foot care education tailored to educational needs compared with no intervention. Finally, six studies described the effect of intensive compared with brief educational interventions. Pooling of outcome data was precluded by marked, mainly clinical, heterogeneity. Four RCTs assessed the effect of patient education on primary end-points: foot ulceration and amputations. One of these studies reported a statistically significant benefit of one hour group education after one year of follow-up in people with diabetes who were at high risk for foot ulceration; RR amputation 0.33 (95% CI 0.15 to 0.76); RR ulceration 0.31 (95% CI 0.14 to 0.66), however this study was at high risk of bias and may have overestimated the effect due to a unit of analysis error. One similar, but methodologically superior study did not confirm this finding; RR amputation 0.98 (95% CI 0.41 to 2.34); RR ulceration 1.00 (95% CI 0.70 to 1.44). The other two studies did not detect any effect of education on ulcer incidence or amputation but were underpowered. Patients' foot care knowledge was improved in the short term in five of eight RCTs in which this outcome was assessed, as was patients' self reported self care behaviour in the short term in seven of nine RCTs. The effects on callus, nail problems and fungal infections were described in five of the included studies, of which only two reported temporary improvements after an educational intervention.Only one of the included RCTs was considered to be at low risk of bias. AUTHORS' CONCLUSIONS: Most of the RCTs included in this review are at high or unclear risk of bias. In some trials, foot care knowledge and self reported patient behaviour seem to be positively influenced by education in the short term. This, however, must be viewed with caution. The ultimate goal of educational interventions is preventing foot ulceration and amputation but only four RCTs reported these outcomes and only two reported sufficient data to examine this. Based on these two studies, we conclude that there is insufficient robust evidence that limited patient education alone is effective in achieving clinically relevant reductions in ulcer and amputation incidence.Future research should focus on evaluating the effect of more comprehensive and/or intensive prevention strategies which may also include patient education (complex interventions).

Complex interventions for preventing diabetic foot ulceration.

BACKGROUND: Ulceration of the feet, which can lead to the amputation of feet and legs, is a major problem for people with diabetes mellitus, and can cause substantial economic burden. Single preventive strategies have not been shown to reduce the incidence of foot ulceration to a significant extent. Therefore, in clinical practice, preventive interventions directed at patients, health care providers and/or the structure of health care are often combined (complex interventions). OBJECTIVES: To assess the effectiveness of complex interventions on the prevention of foot ulcers in people with diabetes mellitus compared with single interventions, usual care or alternative complex interventions. A complex intervention is defined as an integrated care approach, combining two or more prevention strategies on at least two different levels of care: the patient, the healthcare provider and/or the structure of healthcare. SEARCH STRATEGY: Eligible studies were identified by searching the Cochrane Wounds Group Specialised Register (28/05/09), the Cochrane Central Register of Controlled Trials (CENTRAL, 28 May 2009), Ovid MEDLINE (1950 to May Week 3 2009), Ovid EMBASE (1980 to 2009 Week 21) and EBSCO CINAHL (1982 to May Week 4 2009). SELECTION CRITERIA: Prospective randomised controlled trials (RCTs) which compared the effectiveness of combinations of preventive strategies, not solely patient education, for the prevention of foot ulcers in people with diabetes mellitus, with single interventions, usual care or alternative complex interventions. DATA COLLECTION AND ANALYSIS: Two review authors were assigned to independently select studies, to extract study data and to assess risk of bias of included studies, using predefined criteria. MAIN RESULTS: Only five RCTs met the criteria for inclusion. The study characteristics differed substantially in terms of health care settings, the nature of the interventions studied and outcome measures reported. In three studies that compared the effect of an education centred complex intervention with usual care or written instructions only, little evidence of benefit was found. Two studies compared the effect of more intensive and comprehensive complex interventions with usual care. One of these reported improvement of patients' self care behaviour. In the other study a significant and cost-effective reduction of lower extremity amputations (RR 0.30 (95% CI 0.13 to 0.71)) was achieved. All five included RCTs were at high risk of bias; with hardly any of the predefined quality assessment criteria met. AUTHORS' CONCLUSIONS: There is no high quality research evidence evaluating complex interventions for preventing diabetic foot ulceration and insufficient evidence of benefit.

Somatic chronic diseases and 6-year change in cognitive functioning among older persons.

The influence of seven highly prevalent somatic chronic diseases on changes in cognitive functioning is investigated in older persons in a prospective design covering a 6-year follow-up period. The data were collected as part of the Longitudinal Aging Study Amsterdam (LASA). The associations between chronic diseases and cognitive functioning during 6 years of follow-up were analyzed among 1358 respondents (age 62-85) using generalized estimated equations (GEE). Cognitive tests were used to assess: general cognitive functioning, fluid intelligence, information processing speed and memory performance. In the fully adjusted models diabetes mellitus, stroke and peripheral artherosclerosis were associated with cognitive decline during a 6-year follow-up period in older persons. In the unadjusted models cardiac disease was negatively associated with memory function. However, after the correction for possible confounders this association became positive. Cancer was also associated with better memory function. A faster decline in especially memory function was found for diabetes mellitus, stroke, cancer, and peripheral artherosclerosis. The study shows that in older persons specific chronic diseases (diabetes mellitus, stroke, cancer, and peripheral artherosclerosis) are associated with decline in one or more domains of cognitive functioning during a 6-year follow-up period. These findings further stress that careful clinical evaluation of cognitive functioning in older persons with these diseases is required in order to provide adequate care.

Phaeochromocytoma in children.

Phaeochromocytoma is a rare clinical entity in children. Contrary to traditional teaching, which suggested that 10% of phaeochromocytomas are "familial", a germline mutation has been identified in up to 59% (27/48) of apparently sporadic phaeochromocytomas presenting at 18 years or younger and in 70% of those presenting before 10 years of age. The inherited predisposition may be attributable to a germline mutation in the Von Hippel-Lindau gene, the genes encoding the subunits B and D of succinate dehydrogenase, the RET proto-oncogene predisposing to multiple endocrine neoplasia type 2, or the neurofibromatosis type 1 gene. Of these, the Von Hippel-Lindau gene is the most commonly mutated gene in children presenting with a phaeochromocytoma. Genetic counselling is recommended before gene testing and investigation of the wider family. This review provides guidance on the aetiology, investigation, management, histopathology, genetics and follow-up of children with a phaeochromocytoma.

Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates sexual dimorphism.

BACKGROUND: A recent study suggested that sexual dimorphism affects initial thyroid function in congenital hypothyroidism (CH) but differs according to aetiology of CH. AIMS: To determine if sexual dimorphism was associated with biochemical severity of CH and its aetiology in our large British population. METHODS: We examined retrospectively the initial thyroid function tests of 140 infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate radionuclide scans at diagnosis to establish the aetiology of CH prior to commencement of treatment. Patients were classified into athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males and females were made within the three aetiological groups for gestational age, birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression. RESULTS: There was no significant difference between sexes for gestation, birth weight and initial treatment dose in all aetiological subgroups. In thyroid ectopia, screening TSH and confirmatory plasma TSH were significantly higher in females compared with males (P < 0.01), while confirmatory plasma T4 were significantly lower in females (P < 0.05). No difference was detected between males and females in athyreosis and dyshormonogenesis subgroups for screening TSH, confirmatory plasma TSH and total T4. CONCLUSION: Sexual dimorphism influenced the biochemical severity of thyroid ectopia in congenital hypothyroidism in our British population. However, this effect was not apparent in patients with athyreosis or dyshormonogenesis. Further advances in the molecular genetics of CH are essential to evaluate this phenomenon further.

Functional characterization of a novel insulin receptor mutation contributing to Rabson-Mendenhall syndrome.

OBJECTIVE/PATIENTS: Rabson-Mendenhall syndrome (RMS) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene. We have identified a pair of siblings with RMS attributable to compound heterozygosity for two insulin receptor mutations, one previously unreported, and have characterized the novel receptor mutation functionally. MEASUREMENTS: Insulin receptor sequencing was performed to identify the mutations. Expression levels of the mature receptor were determined in lymphoblastoid cells from the affected subjects. Further studies of immortalized cell lines transfected with mutant and wild type (WT) receptors were undertaken to characterize the effects of the novel mutation on [(125)I]-labelled insulin binding, proreceptor processing and insulin-stimulated receptor autophosphorylation. RESULTS: Sequencing of the insulin proreceptor coding sequence revealed both siblings to be compound heterozygotes for the missense mutations Arg209His and Gly359Ser in the mature insulin receptor. The former mutation has been described in homozygous form in Donohue syndrome, while the latter is novel. Insulin receptor expression in lymphoblastoid cell lines was present at only 10-30% of that in control cells; studies of immortalized cells transfected with mutant and WT receptors confirmed the reduced expression of the mutant. The degree of impairment of insulin binding and insulin-stimulated receptor autophosphorylation were commensurate with the decrease in expression of the mature receptor. CONCLUSIONS: Loss of function of the novel insulin receptor (INSR) G359S variant is largely accounted for by aberrant proreceptor processing rather than intrinsically impaired signal transduction by the mutant receptor.

Predictors of survival in nursing home patients with severe dementia in whom artificial nutrition and hydration are [corrected] forgone.

BACKGROUND: To investigate the characteristics of patients in whom artificial nutrition and hydration (ANH) is forgone, duration of survival after the decision and factors that are associated with duration of survival. METHODS: Observational study based on written questionnaires in 32 Dutch nursing homes. Of 178 nursing home patients with dementia, their treating nursing home physician (NHP) filled in a questionnaire directly after the decision was made to forgo ANH. The maximum follow-up was 6 weeks. Cox proportional hazards analysis was used to determine predictors of survival. RESULTS: Decisions to forgo ANH in Dutch nursing homes were made most often in patients with severe dementia who also had an acute illness. More than half the patients (59%) died within 1 week after the decision. Patients with dyspnea and/or apathy were more likely to die during follow-up than patients without these symptoms. Patients who were considered more severely ill by the NHP were more likely to die than those who were considered less severely ill. The presence of restlessness indicated a higher chance of survival. CONCLUSIONS: The clinical judgment of the NHP of the severity of illness appeared to be a strong predictor of patient survival. NHPs should not rely solely on their clinical judgment concerning survival, but they should also consider the presence or absence of dyspnea, apathy and restlessness.

Discomfort in nursing home patients with severe dementia in whom artificial nutrition and hydration is forgone.

BACKGROUND: While there is debate about whether it may be better to forgo than to initiate artificial nutrition and hydration (ANH) in nursing home patients with severe dementia, the consequences of forgoing ANH in these patients, in particular their discomfort, have not yet been investigated. METHODS: In this prospective, longitudinal, observational study of 178 patients in Dutch nursing homes, discomfort was measured at all measurement times according to the observational Discomfort Scale-Dementia of Alzheimer Type. Furthermore, at all measurement times, plausible determinants of discomfort were registered. Data were analyzed with the statistical technique of generalized estimated equations. RESULTS: Decisions to forgo ANH were made most often in severely demented, female patients with an acute illness as the most important diagnosis at that time. The mean level of discomfort was highest at the time of the decision and decreased in the days thereafter. There were substantial differences in level of discomfort between patients. Dyspnea, restlessness, and physicians' observations of pain and dehydration were associated with higher levels of discomfort. Furthermore, patients who were awake had higher levels of observed discomfort than patients who were asleep. CONCLUSIONS: Forgoing ANH in patients with severe dementia who scarcely or no longer eat or drink seems, in general, not to be associated with high levels of discomfort. The individual differences emphasize the need for constant attention for possible discomfort.

Multivariate analysis on factors affecting suppression of thyroid-stimulating hormone in treated congenital hypothyroidism.

AIMS: To determine the factors which influence the suppression of thyroid-stimulating hormone (TSH) in infants with congenital hypothyroidism (CH) following treatment. METHODS: We examined retrospectively the patterns of thyroid function tests from diagnosis to 3 years of age in 140 infants diagnosed with CH from screening. Patients were classified into 3 groups: athyreosis, ectopia and presumed dyshormonogenesis on the basis of thyroid scans. Adequate TSH suppression was defined as plasma TSH concentration <6 mU/l. The factors affecting the suppression of TSH at 6 months and 1 year of age which were evaluated were: initial confirmatory plasma TSH, initial plasma thyroxine (T4), mean age of starting treatment with L-T4, dose of L-T4 at diagnosis, 6 weeks, 3 months and 6 months, and aetiology of the congenital hypothyroidism. Variables were then entered in a stepwise logistic regression model for TSH suppression at 6 months and 1 year of age. RESULTS: All infants had radionuclide scans prior to treatment: athyreosis (n = 39), ectopia (n = 78) and dyshormonogenesis (n = 23). 58% of patients had persistently raised TSH at 6 months of age while 31% of patients had a persistently raised TSH at 1 year of age. There was a significant delay in the normalisation of plasma TSH in athyreosis and ectopia groups compared with dyshormonogenesis. Multiple regression analysis for TSH suppression at 6 months of age found plasma T4 levels and aetiology of CH as independent factors affecting the timing of TSH suppression. Aetiology of CH was the only independent factor affecting TSH suppression at 1 year of age. CONCLUSION: At 6 months of age, plasma T4 levels at 6 weeks and 3 months, and aetiology of CH were independent factors affecting timing of TSH suppression. However, by 1 year of age, the aetiology of CH was the only independent factor affecting suppression of TSH.

Children with congenital hypothyroidism are at risk of adult obesity due to early adiposity rebound.

OBJECTIVE: There is some evidence that children with congenital hypothyroidism (CH) are heavier than their reference population. There are few data on adults with CH. The timing of adiposity rebound (AR) in childhood has been shown to have strong correlations with adult obesity. Our aims were to study the timing of AR and factors affecting AR in children with CH. PATIENTS AND METHODS: The timing of AR was examined in a retrospective study of children with CH with growth data at least up to 5 years of age. The proportion of children with CH who reached AR by 37 months and by 49 months of age were compared with healthy children and children with acute lymphoblastic leukaemia (ALL) described in the literature. Correlation of timing of AR with body mass index (BMI) standard deviation score (SDS) at 10 years, initial severity of hypothyroidism and age at normalization of TSH were examined. Multiple logistic regression was used to identify independent factors associated with BMI > or = 20 (overweight) at 10 years of age. RESULTS: The study included 53 children (34 females and 19 males). AR had occurred by 37 months in 37.7% children with CH, in 42.7% children treated for ALL (CH vs. ALL, P = 0.58) and in 4.5% healthy British children (CH vs. normal, P < 0.0001). We found that 54.7% children with CH had reached AR compared with 21.4% of normal children (CH vs. normal, P < 0.0001) by the age of 49 months. Timing of AR showed significant negative correlation with BMI SDS at 10 years (r = -0.487, P = 0.01). There were no significant relationships between timing of AR and initial thyroid function or age at normalization of TSH. Multiple logistic regression analysis identified age at AR as an independent factor associated with BMI > or = 20 at 10 years of age (P = 0.04). CONCLUSIONS: Children with CH showed significantly earlier AR compared to normal British children. This showed significant negative correlation with BMI SDS at 10 years. AR in CH does not appear to be directly related to the initial severity of hypothyroidism or to treatment factors.

Quality of care for patients with type 2 diabetes mellitus in the Netherlands and the United States: a comparison of two quality improvement programs.

OBJECTIVE: To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs. STUDY SETTING: Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group-model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997. STUDY DESIGN: In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self-management support. DATA COLLECTION: Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. PRINCIPAL FINDINGS: In the EMC process outcomes and glycemic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow-up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines. CONCLUSIONS: Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects.

Chronic diseases and depression: the modifying role of psychosocial resources.

Psychosocial coping resources have been found to protect against depressive symptoms in people with and without chronic diseases. It has not been established, however, whether these resources have the same effects across patients with different diseases. Therefore, the aim of the study was to estimate the direct and buffer effects of psychosocial resources on depression, and to examine whether these effects are different for various chronic diseases. Data were obtained from the Longitudinal Aging Study Amsterdam. In all, 2288 community-dwelling respondents (age 55-85) were included and followed for a maximum of 6 years. Depressive symptoms (using the Center for Epidemiologic Studies-Depression scale), the presence of seven frequently occurring chronic diseases, social support and personal coping resources, physical functioning and sociodemographic variables were assessed by structured interviews. Generalized estimating equation models were estimated for each disease, social support and personal coping resources. All resources, except social network size, showed a direct effect on depressive symptoms regardless of the presence of chronic diseases. Having a partner, high self-esteem, mastery, self-efficacy and feeling less lonely additionally buffered the negative effect of some, but not all, specific chronic diseases. Unexpectedly, in patients with cardiac disease, none of the psychosocial resources exerted a buffer effect on depressive symptoms. For instrumental and emotional support only direct (unfavorable) effects and no buffer effects could be observed. In conclusion, our study provides evidence that buffer effects of psychosocial resources are different across various chronic diseases. This suggests that interventions to enhance specific resources may ameliorate depressive symptoms in specific chronic patients groups.