Comparing patient-reported outcomes entered at home versus at hospital, and testing touch screens for initial recruitment to scientific trials in arthritis patients.

OBJECTIVES: Touch screens for entering patient-reported outcomes (PROs) are available at all Danish departments of rheumatology reporting to the nationwide DANBIO registry. This project comprises two substudies in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (AxSpA), aiming to (A) investigate the feasibility of first line patient recruitment for research via touch screens, and (B) compare PROs collected at hospital versus at home, including patient preferences. METHOD: Substudy A: using a touch screen, patients answered whether we could contact them about a clinical research project (yes/no). Characteristics of patients who accepted/declined were explored using chi-squared and Mann-Whitney U-tests. Substudy B (randomized crossover agreement study): a random sample of patients from the accepting group in substudy A was contacted by telephone. According to prespecified power and sample size estimation, 56 patients were included. After randomization, 50% of patients entered PROs and information on comorbidities and lifestyle from home and then at hospital, and 50% first from hospital and then at home. Finally, they stated their preference for data entry (hospital/home/equally good). Differences in PROs entered from home and in the hospital were compared (limits of agreement, 95% confidence intervals, and intraclass correlation coefficients). RESULTS: The touch-screen invitation was accepted by 428/952 patients (45%). Patients who accepted and those who declined had similar PROs and demographics. Substudy B was completed by 42 patients (22 RA, 20 AxSpA). They had no significant differences between PROs and lifestyle/comorbidity data entered from home and hospital, except for AxSpA patients on the Bath Ankylosing Spondylitis Functional Index and Bath Ankylosing Spondylitis Disease Activity Index item 5. The preferred method of data entry was hospital (10%), home (50%), and equally good (40%). CONCLUSION: Touch screens seem feasible for first line research recruitment. PROs collected from home were similar to the touch-screen solution. Patients preferred data entry from home.

Differential hypothalamic leptin sensitivity in obese rat offspring exposed to maternal and postnatal intake of chocolate and soft drink.

BACKGROUND/OBJECTIVE: Intake of high-energy foods and maternal nutrient overload increases the risk of metabolic diseases in the progeny such as obesity and diabetes. We hypothesized that maternal and postnatal intake of chocolate and soft drink will affect leptin sensitivity and hypothalamic astrocyte morphology in adult rat offspring. METHODS: Pregnant Sprague-Dawley rats were fed ad libitum chow diet only (C) or with chocolate and high sucrose soft drink supplement (S). At birth, litter size was adjusted into 10 male offspring per mother. After weaning, offspring from both dietary groups were assigned to either S or C diet, giving four groups until the end of the experiment at 26 weeks of age. RESULTS: As expected, adult offspring fed the S diet post weaning became obese (body weight: P<0.01, %body fat per kg: P<0.001) and this was due to the reduced energy expenditure (P<0.05) and hypothalamic astrogliosis (P<0.001) irrespective of maternal diet. Interesting, offspring born to S-diet-fed mothers and fed the S diet throughout postnatal life became obese despite lower energy intake than controls (P<0.05). These SS offspring showed increased feed efficiency (P<0.001) and reduced fasting pSTAT3 activity (P<0.05) in arcuate nucleus (ARC) compared with other groups. The findings indicated that the combination of the maternal and postnatal S-diet exposure induced persistent changes in leptin signalling, hence affecting energy balance. Thus, appetite regulation was more sensitive to the effect of leptin than energy expenditure, suggesting differential programming of leptin sensitivity in ARC in SS offspring. Effects of the maternal S diet were normalized when offspring were fed a chow diet after weaning. CONCLUSIONS: Maternal intake of chocolate and soft drink had long-term consequences for the metabolic phenotype in the offspring if they continued on the S diet in postnatal life. These offspring displayed obesity despite lowered energy intake associated with alterations in hypothalamic leptin signalling.

Mental health in early pregnancy is associated with pregnancy outcome in women with pregestational diabetes.

AIM: To explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes. METHODS: This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30 with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (< 37 weeks) and large for gestational age infants (birth weight > 90(th) percentile). Differences between groups in the questionnaires were analysed using an unpaired t-test. RESULTS: Women with preterm deliveries (n = 28) had lower (i.e. worse) mean (sd) quality-of-life scores for the two 36-item Short-Form Health Survey scales, Role-Emotional [58.3 (38.1) vs. 82.9 (31.3); P = 0.0005] and Mental Health [67.7 (20.4) vs. 75.2 (15.8), P = 0.04], and a lower score for the 36-item Short-Form Health Survey scale Mental Component Summary (42.8 (13.1) vs. 48.8 (9.7), P = 0.03) in early pregnancy, compared with women with term deliveries. Depression symptoms (Hospital Anxiety and Depression Scale depression score ≥ 8) were more frequent in women with preterm vs. term deliveries (seven (25%) vs. six women (5%); P = 0.003), while levels of anxiety and locus of control were similar in these two groups. No difference in early pregnancy scores for health-related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants. CONCLUSIONS: Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational diabetes.

Real-time continuous glucose monitoring as a tool to prevent severe hypoglycaemia in selected pregnant women with Type 1 diabetes - an observational study.

AIMS: Among women with Type 1 diabetes who have had severe hypoglycaemia the year before pregnancy, 70% also experience this complication in pregnancy, and particularly in the first half of pregnancy. We evaluated whether routine use of real-time continuous glucose monitoring from early pregnancy onwards could prevent severe hypoglycaemia in these women. METHODS: All 136 consecutive pregnant women with Type 1 diabetes referred to our centre were asked about severe hypoglycaemic events in the year before pregnancy and early in pregnancy at their first antenatal visit. Women with a relevant recent history were informed about their additional high risk of severe hypoglycaemia, their treatment was focused on restricted insulin doses during the first 16 gestational weeks, and they were offered real-time continuous glucose monitoring on top of self-monitored plasma glucose measurements. RESULTS: Among 28 women with a recent history of severe hypoglycaemia, 12 (43%) used real-time continuous glucose monitoring from a median (range) of 10 (7-13) gestational weeks for 10 (1-32) weeks. Among these 12 women, eight had experienced a total of 34 (range 1-11) severe hypoglycaemic events in the year before pregnancy and nine had experienced 23 (range 1-10) events early in pregnancy. After initiation of real-time continuous glucose monitoring, two (17%) women experienced one event each. The incidence rates of severe hypoglycaemia were 2.8,17.5 and 0.3 events/patient-year. Among the 16 women in the high risk group not using real-time continuous glucose monitoring, the corresponding figures were 1.6, 5.0 and 0.1 events/patient-year. CONCLUSIONS: Further evaluation is required to determine whether continuous real-time continuous glucose monitoring from early pregnancy onwards in highly selected women may reduce the risk of severe hypoglycaemia. Other elements of focused intervention probably also contribute to the risk reduction.

The incidence of severe hypoglycaemia in pregnant women with type 1 diabetes mellitus can be reduced with unchanged HbA1c levels and pregnancy outcomes in a routine care setting.

AIMS: To investigate whether the incidence of severe hypoglycaemia in pregnant women with type 1 diabetes can be reduced without deteriorating HbA1c levels or pregnancy outcomes in a routine care setting. METHODS: Two cohorts (2004-2006; n=108 and 2009-2011; n=104) were compared. In between the cohorts a focused intervention including education of caregivers and patients in preventing hypoglycaemia was implemented. Women were included at median 8 (range 5-13) weeks. Severe hypoglycaemia (requiring assistance from others) was prospectively reported in structured interviews. RESULTS: In the first vs. second cohort, severe hypoglycaemia during pregnancy occurred in 45% vs. 23%, p=0.0006, corresponding to incidences of 2.5 vs. 1.6 events/patient-year, p=0.04. Unconsciousness and/or convulsions occurred at 24% vs. 8% of events. Glucagon and/or glucose injections were given at 15% vs. 5% of events. At inclusion HbA1c was comparable between the cohorts while in the second cohort fewer women reported impaired hypoglycaemia awareness (56% vs. 36%, p=0.0006), insulin dose in women on multiple daily injections was lower (0.77 IU/kg (0.4-1.7) vs. 0.65 (0.2-1.4), p=0.0006) and more women were on insulin analogues (rapid-acting 44% vs. 97%, p<0.0001; long-acting 6% vs. 76%, p<0.0001) and insulin pumps (5% vs. 23%, p<0.0001). Pregnancy outcomes were similar in the two cohorts. CONCLUSIONS: A 36% reduction in the incidence of severe hypoglycaemia in pregnancy with unchanged HbA1c levels and pregnancy outcomes was observed after implementation of focused intervention against severe hypoglycaemia in a routine care setting. Improved insulin treatment, increased health professional education and fewer women with impaired hypoglycaemia awareness may contribute.

Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes - observations from a randomized controlled trial.

AIMS: To explore whether real-time continuous glucose monitoring during labour and delivery supplementary to hourly self-monitored plasma glucose in women with Type 1 diabetes reduces the prevalence of neonatal hypoglycaemia. METHODS: Women with Type 1 diabetes participating in a randomized controlled trial on the effect of real-time continuous glucose monitoring in pregnancy were included in this study. Twenty-seven of 60 (45%) women in the intervention arm used real-time continuous glucose monitoring during labour and delivery, supplementary to hourly self-monitored plasma glucose. Real-time continuous glucose monitoring glucose data covering the last 8 h prior to delivery were retrospectively evaluated, and maternal hypo- and hyperglycaemia were defined as glucose values ≤ 3.9 mmol/l and > 7.0 mmol/l, respectively. Women in the control arm (n = 59) solely used self-monitored plasma glucose. Neonatal hypoglycaemia was defined as a 2-h plasma glucose < 2.5 mmol/l. RESULTS: In infants of women using real-time continuous glucose monitoring during labour and delivery, 10 (37%) developed neonatal hypoglycaemia vs. 27 (46%) infants in the control arm (P = 0.45). Among 10 infants with and 17 infants without neonatal hypoglycaemia within the real-time continuous glucose monitoring arm, median maternal self-monitored plasma glucose was 6.2 (range 4.2-7.8) vs. 5.6 (3.3-8.5) mmol/l (P = 0.26) during labour and delivery, with maternal hyperglycaemia present in 17 (0-94) vs. 4 (0-46)% of the time (P = 0.02), and birthweight was 4040 (3102-4322) vs. 3500 (1829-4320) g (P = 0.04). Maternal hypoglycaemia up to delivery was relatively rare. CONCLUSIONS: The prevalence of neonatal hypoglycaemia was comparable between infants of women using real-time continuous glucose monitoring supplementary to self-monitored plasma glucose during labour and delivery and infants of women solely using self-monitored plasma glucose.

Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes.

AIM: To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. METHODS: Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring for 6 days at median 9 (range 6-14) gestational weeks and were asked to answer a semi-structured questionnaire on patient satisfaction. RESULTS: Median HbA1c was 49 (range 34-86) mmol/mol) [6.6 (5.3-10.0) %] and duration of diabetes was 12 (0.5-37) years. Continuous glucose monitoring was used for 6 (0.5-7) days, with 43 (65%) women using continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0-12) alarms per 24 h, of which approximately one third was technical alarms and one third disturbed their sleep. Sixteen women (24%) reported discomfort with continuous glucose monitoring during daytime and twelve (18%) during sleep. Many women reported improved diabetes understanding (52%) and would recommend continuous glucose monitoring to others (83%). Twenty-four patients (36%) had continuous glucose monitoring removed earlier than planned ( before the intended 6 days of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found in continuous glucose monitoring use, inconvenience or compliance with respect to diabetes type. CONCLUSIONS: The majority of pregnant women with diabetes found real-time continuous glucose monitoring useful and the intervention was equally tolerated regardless of diabetes type. Nevertheless, continuous glucose monitoring was frequently removed earlier than planned, primarily because of skin irritation, technical problems and inaccuracy.

[1997-2007, 10 years of monitoring the evolution of resistance of Streptococcus pneumoniae to antibiotics in the region Centre; review of the Pneumococcus network]. / 1997-2007, dix ans de suivi de l'évolution de la résistance de Streptococcus pneumoniae aux antibiotiques en région Centre; bilan de l'observatoire du pneumocoque.

Regional pneumococcal observatories in region Centre, created in 1997, participate with the others pneumococcal observatories alongside the National Reference Center for Pneumococci and the Institut de Veille Sanitaire at the monitoring of the evolution of resistance of pneumococci to antibiotics in France. Between 1997 and 2007, 2427 strains of Streptococcus pneumoniae were isolated in part from cerebrospinal fluids, blood and middle ear fluid, from children and adults. The prevalence of pneumococci with a decreased susceptibility to penicillin (PDSP) decreased strongly in region Centre: 56.8 % in 2001, 39.6 % en 2007. These data are similar to the French national data over the same period.

[The Pneumococcal Observatory for the Central Region, 1 April 1999 to 31 March 2000]. / Observatoire du Pneumocoque de la Région Centre, du 1er avril 1999 au 31 mars 2000.

Seven hundred and ninety six strains of pneumococcus were collected in the Centre region, from 15 laboratories, between 1st April 1999 and 31st of March 2000. Data were processed, using 4th dimension software, and concerned age, file number, consultation/hospitalisation, sample type, susceptibility to oxacillin (5 micrograms), results of the E-test for benzylpenicillin, amoxicillin, cefotaxime and results of the routine disc diffusion test. Strains with reduced susceptibility to benzylpenicillin (PRSP) were collected by the co-ordinating centre to perform MICs by the reference agar dilution test and serotyping. Out of 796 strains, 450 strains (56.7%) were categorised as PRSP and 400 of them were studied by the co-ordinating centre. Forty two percent of the samples originated from lungs, followed by 19.5% from blood samples, 15% from ear pus (85.7% PRSP) and 2.5% from CSF. Thirty nine percent of the patients were female. 36.6% were children under sixteen (70.1% PRSP) and 62.4% were adults (49.2% PRSP). Out of 400 PRSP 106 (26.5%) were characterised as resistant and 294 (73.5%) as intermediate to benzylpenicillin. Compared to the agar dilution test, 90% of the PRSP studied by E-test had a MIC value for benzylpenicillin within +/- 1 dilution. Thirty six strains of PRSP were resistant to amoxicillin (9% of the PRSP) and 10 (2.5% of the PRSP) to cefotaxime. Serotyping was done on 375 strains. The serotypes encountered were the following: 23 (26.9%), 14 (22.1%), 19 (19.5%), 6 (12.8%), 9 (9.9%) and 15 (5.1%).

[The Pneumococcus Observatory of the Central Region, from June 1, 1997 to May 31, 1998]. / Observatoire du pneumocoque de la région Centre, du 1er juin 1997 au 31 mai 1998.

714 pneumococcus were listed from 14 laboratories between the 1 June 1997 and the 31 May 1998. Data capture was done on Epi info software and concerned age, file number, consultation/hospitalization, sample type, susceptibility to oxacilline (5 micrograms), the results of the E-test for penicillin G, amoxicillin, cefotaxime and the results of the routine disk diffusion susceptibility method. Strains with reduced susceptibility to penicillin G (PRSP) were collected by the coordinating center to perform MICs by the reference method of agar dilution and serotyping. Over 714 strains, 45.7% of the samples originated from lungs, followed by 22% for blood samples, 14% for ear pus and 2.3% for CSF. 34% of the patients were female. 36.7% were children under 16 (57.8% PRSP) and 63.3% were adults (41% PRSP). 338 strains (47.3%) were determined as PRSP and 293 of them were studied by the coordinating center. 81 of the 293 PRSP (27.7%) were resistant et 212 (72.3%) were intermediate to penicillin G. 81% of the PRSP studied had a CMI value for penicillin G within +/- 1 log2 dilution. 20 strains of PRSP were resistant for amoxicillin (6.8% of the PRSP) and two (0.7% of the PRSP) for cefotaxime. 289 serotyping were done, most met serotypes were 23 (25%), 14 (23%). The least met was 15 (2.4%). These results let assess the epidemiology of pneumococcus in our region.

Allergy risk in an enzyme producing plant: a retrospective follow up study.

OBJECTIVE: To investigate the risk of enzyme sensitisation and clinical allergy in workers exposed to enzymes at Novo Nordisk A/S. METHODS: The study was a retrospective follow up study based on medical history and test data originally collected at routine screenings for enzyme allergy by the Occupational Health Service (OHS) of Novo Nordisk A/S during the period 1970-92. Workers were exposed to proteases, lipases, cellulases, and carboxyhydrases. Medical records of 3815 subjects were registered in the OHS database. According to criteria including possible enzyme exposure, allergy tests at the time of engagement, and participation in the allergy screening programme 1064 were selected for the present study. Outcomes were allergy symptoms, specific IgE test (radioallergosorbent test (RAST)) to enzymes, skin test reactions to common allergens and enzymes, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Potential risk factors were smoking habits, workplace, type of job, age, and sex. RESULTS: Sensitisation occurred to all types of enzymes handled in the plant, most often in production areas and laboratories; 8.8% developed clinical enzyme allergy during the first three years of employment. The risk declined during the period. The frequency of enzyme sensitisation, expressed as RAST values > 0.5 SU, was 36%, and the frequency of significant RAST values > or = 2 SU was 8%. Ranking diagnoses of enzyme allergy by severity, the frequency of asthma was 5.3%, rhinitis 3.0%, and urticaria 0.6%. Half of the cases occurred within the first 15 months of exposure. Smoking was an independent risk factor for clinical enzyme allergy (odds ratio (OR) = 2.3 (95% exact confidence interval (95% CI) 1.4 to 3.9), measurable RAST > or = 0.5 SU (OR = 1.5 (95% CI 1.1 to 2.1)), and RAST > or = 2 SU (OR = 4.5 (95% CI 2.2 to 8.4)). Atopic predisposition at the time of engagement was not a significant risk factor for enzyme allergy. This could be due to various selection mechanisms.