Establishing priorities for European collaboration in communicable disease surveillance

Background: Several collaborations in communicable disease surveillancehave developed between European Union member states. Involvementin these activities takes time and money. It is vital that collaborationsare established in areas most likely to be beneficial. An exercisewas undertaken to inform national surveillance centres and theEuropean Commission as to priority areas for the developmentof collaborations. Methods: A modified Delphi exercise was undertakenamongst the heads of centres with responsibilities for surveillanceat national level in the member states of the EU. Participantsdeveloped, agreed and ranked criteria for developing collaborations.A list of communicable diseases and syndromes was then rankedusing a Likert-type scale. Three rounds were undertaken. Betweenrounds, scores and a ranking were fed back showing where participantshad ranked items, compared to the overall mean and rank distribution.For the third round participants were asked to use a categoricalscale, nominating six or ten high priority disease areas. Results:Response rates were 87.5% for round 1, 44% round 2 and 87% round3. The low round 2 response rate appeared to be because respondentsdid not wish to alter their rankings. The six high priorityareas were outbreaks of gastroenteritis/food poisoning, CID/otherslow virus infections, serious imported diseases, legionellosis,antimicrobial resistance and tuberculosis. When participantsgave ten high priority areas meningococcal disease, travel advice,vaccination/immunization and influenza were also included. Thefinal lists were accepted at the meeting of participants. Conclusions:The process was successful in developing both a priority listand consensus.     

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses

Doppler echocardiographic characteristics of normally functioningAllcarbon prostheses were studied in 149 consecutive patientswith 157 valves in the mitral (n=73) and aortic (n=84) positionswhose function was considered normal by clinical and echocardiographicevaluation. In the mitral position, the mean gradient and theeffective mitral orifice area were not significantly differentin either the 25-mm or the 31-mm size valves (from 5±1to 4±1 mmHg and from 2.2±0.6 to 2.8±0.9cm², respectively; P=ns for both). Conversely, peak gradientwas significantly and inversely correlated to actual orificearea (r=–0.70; P<0.0006), decreasing from 15±3mmHg in the 25-mm size valve to 9±1 mmHg in the 31-mmsize. In the aortic position, the mean gradient was 29±8 mmHgin the 19-mm size valve; it decreased to 8±2 mmHg inthe 29-mm size. Effective prosthetic aortic valve area, calculatedusing the continuity equation, ranged between 0.9±0.1cm² for the 19-mm size valve to 4.1±0.7 cm² for the 29-mmsize. By analysis of variance, effective prosthetic aortic valvearea differentiated various valve sizes (F=25.3; P<0.0001)better than peak (F=5.34; P=0.012) or mean (F=4.34; P=0.0052)gradients alone, and it correlated better with actual orificearea (r=0.89, r=–0.70 and r=–0.65, respectively).This study provides the normal range for Doppler haemodynamiccharacteristics of the various sizes of the Allcarbon valvein the mitral and aortic positions so that prosthetic malfunctioncan be identified.     

Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implications

Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.     

Relationships between inflammation,hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFR_INULIN, ERPF_PAH, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng?kg^?1?min^?1). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFR_INULIN correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.     

Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes

OBJECTIVE

Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes.

RESEARCH DESIGN AND METHODS

Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO₂peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR.

RESULTS

Adolescents (15.5 ± 2.2 years of age) with type 1 diabetes (6.3 ± 3.8 years diabetes duration) had reduced VO₂peak (31.5 ± 6.3 vs. 36.2 ± 7.9 mL/kg ⋅ min, P = 0.046) and VO₂peak/lean kg (43.7 ± 7.0 vs. 51.0 ± 8.6 mL/lean kg ⋅ min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO₂peak and VO₂peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA_1c level, systolic blood pressure, and LDL cholesterol level (β ± SE, VO₂peak: −0.19 ± 0.07, P = 0.02; VO₂peak/lean kg: −0.19 ± 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex- and Tanner-adjusted VO₂peak and VO₂peak/lean kg compared with participants in the lowest tertile.

CONCLUSIONS

Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications.     

Is on‐demand treatment effective in patients with severe haemophilia?

Summary. On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.