Visit patterns at primary care centres and individual blood pressure level - a cross-sectional study.

OBJECTIVE: Hypertension is a major cause of cardiovascular disease. Nevertheless, blood pressure (BP) is often inadequately treated. We studied visit patterns at primary health care centres (PHCCs) and their relation to individual BP control. DESIGN AND SETTING: Cross-sectional register-based study on all patients with hypertension who visited 188 PHCCs in a Swedish region. PATIENTS: A total of 88,945 patients with uncomplicated hypertension age 40-79. MAIN OUTCOME MEASURES: Odds ratio (OR) for the individual patient to achieve the BP target of ≤140/90 mmHg. RESULTS: Overall, 63% of patients had BP ≤ 140/90 mmHg (48% BP < 140/90). The PHCC that the patient was enrolled at and, as part of that, more nurse visits at PHCC level was associated with BP control, adjusted OR 1,10 (95% CI 1.01 to 1.21). Patients visiting PHCCs with the highest proportion of visits with nurses had an even higher chance of achieving the BP target, OR 1.19 (95% CI 1.07 to 1.32). CONCLUSIONS: In a Swedish population of patients with hypertension, about half do not achieve recommended treatment goals. Organisation of PHCC and team care are known as factors influencing BP control. Our results suggests that a larger focus on PHCC organisation including nurse based care could improve hypertension care.

Pay for performance associated with increased volume of medication reviews but not with less inappropriate use of medications among the elderly - an observational study.

OBJECTIVE: A pay for performance programme was introduced in 2009 by a Swedish county with 1.6 million inhabitants. A process measure with payment linked to coding for medication reviews among the elderly was adopted. We assessed the association with inappropriate medication for five years after baseline. DESIGN AND SETTING: Observational study that compared medication for elderly patients enrolled at primary care units that coded for a high or low volume of medication reviews. PATIENTS: 144,222 individuals at 196 primary care centres, age 75 or older. MAIN OUTCOME MEASURES: Percentage of patients receiving inappropriate drugs or polypharmacy during five years at primary care units with various levels of reported medication reviews. RESULTS: The proportion of patients with a registered medication review had increased from 3.2% to 44.1% after five years. The high-coding units performed better for most indicators but had already done so at baseline. Primary care units with the lowest payment for coding for medication reviews improved just as well in terms of inappropriate drugs as units with the highest payment - from 13.0 to 8.5%, compared to 11.6 to 7.4% and from 13.6 to 7.2% vs 11.8 to 6.5% for polypharmacy. CONCLUSIONS: Payment linked to coding for medication reviews was associated with an increase in the percentage of patients for whom a medication review had been registered. However, the impact of payment on quality improvement is uncertain, given that units with the lowest payment for medication reviews improved equally well as units with the highest payment.

Serum cytokine pattern in young children with screening detected coeliac disease.

Coeliac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening-detected coeliac disease before and after treatment with a gluten-free diet. Serum samples selected before and after the start of a gluten-free diet from 26 3-year-old children diagnosed with biopsy-proven coeliac disease and from 52 matched controls were assayed in an multiplex enzyme-linked immunosorbent assay (ELISA) for the 10 cytokines: interferon (IFN)-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13 and tumour necrosis factor (TNF)-α. Among Th1 cytokines, IFN-γ and IL-12p70 were elevated significantly in children with coeliac disease compared to controls (P < 0.001 and P = 0.001, respectively). Similar findings were demonstrated for the Th2 cytokines IL-5 (P < 0.001), IL-10 (P = 0.001) and IL-13 (P = 0.002). No difference in cytokine levels between the two groups was found for TNF-α, IL-1ß, IL-2, IL-4 and IL-8. After gluten-free diet, levels of IL-5, IL-12 and IL-10 decreased significantly (P < 0.001, P = 0.002 and P = 0.007) and IFN-γ levels were reduced (P = 0.059). Young children with coeliac disease detected by screening demonstrate elevated levels of serum cytokines at time of diagnosis. A prolonged systemic inflammation may, in turn, contribute to long-term complications known to be associated with untreated coeliac disease.

Short-term effects of a pay-for-performance programme for diabetes in a primary care setting: an observational study.

OBJECTIVE: A pay-for-performance (P4P) programme for primary care was introduced in 2011 by a Swedish county (with 1.6 million inhabitants). Effects on register entry practice and comparability of data for patients with diabetes mellitus were assessed. DESIGN AND SETTING: Observational study analysing short-term outcomes before and after introduction of a P4P programme in the study county as compared with a reference county. SUBJECTS: A total of 84 053 patients reported to the National Diabetes Register by 349 primary care units. MAIN OUTCOME MEASURES: Completeness of data, level and target achievement of glycated haemoglobin (HbA1c), blood pressure (BP), and LDL cholesterol (LDL). RESULTS: In the study county, newly recruited patients who were entered during the incentive programme were less well controlled than existing patients in the register - they had higher HbA1c (54.9 [54.5-55.4] vs. 53.7 [53.6-53.9] mmol/mol), BP, and LDL. The percentage of patients with entry of BP, HbA1c, LDL, albuminuria, and smoking increased in the study county but not in the reference county (+26.3% vs -1.5%). In the study county, with an incentive for BP < 130/80 mmHg, BP data entry behaviour was altered with an increased preference for sub-target BP values and a decline in zero end-digit readings (38.3% vs. 33.7%, p < 0.001). CONCLUSION: P4P led to increased register entry, increased completeness of data, and altered BP entry behaviour. Analysis of newly added patients and data shows that missing patients and data can cause performance to be overestimated. Potential effects on reporting quality should be considered when designing payment programmes. Key points A pay-for-performance programme, with a focus on data entry, was introduced in a primary care region in Sweden. Register data entry in the National Diabetes Register increased and registration behaviour was altered, especially for blood pressure. Newly entered patients and data during the incentive programme were less well controlled. Missing data in a quality register can cause performance to be overestimated.

Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Effect of captopril on renal hemodynamics in the treatment of resistant renal hypertension.

The effects of 6 weeks of treatment with captopril on the renal hemodynamics of 16 patients with treatment-resistant renal hypertension (six had diabetic nephropathy, seven had other renal parenchymatous disease, and three had renovascular disease) were studied. Significant changes in glomerular filtration rate, filtration fraction, plasma renin activity, urinary aldosterone, and mean blood pressure were noted in the patients with renal parenchymatous disease, but not in those with diabetic nephropathy. Renal blood flow remained unchanged in all patients. Captopril was well tolerated.

Renal effects of felodipine in hypertensive patients with reduced renal function.

The new calcium antagonist felodipine with a pronounced arteriolar dilating capacity was used to treat 11 patients with severe hypertension resistant to treatment (4 with essential hypertension, 5 with renoparechymatous hypertension, 2 with renovascular hypertension). Mean glomerular filtration rate for 10 patients was 34 +/- 27 ml/min/1.73 m2 body surface area (51Cr-EDTA clearance) before felodipine. One patient was on haemodialysis treatment. Mean arterial blood pressure in the outpatient clinic was 206 +/- 39/119 +/- 18 mm Hg in spite of treatment with 3 or more antihypertensive drugs. All but 2 patients had been given an angiotensin converting-enzyme inhibitor without success. All vasodilating agents were discontinued and the following morning 5 to 10 mg felodipine was given orally. This resulted in a reduction of average supine blood pressure from 190/110 mm Hg to 150/90 mm Hg during the first hour. The antihypertensive effect was unchanged during 6 hours and the drug was subsequently administered twice or three times a day. Mean systolic and diastolic blood pressure after 1 month was 155 +/- 19/91 +/- 12 mm Hg. Eight patients showed a favourable long term response with a mean systolic and diastolic blood pressure of 154 +/- 17/89 +/- 6mm Hg after 6 months. One patient died from his underlying disease after 2 months and 1 patient discontinued treatment because of ankle oedema after 6 weeks. In the long term treated patients with glomerular filtration rates greater than 15 ml/min/1.73m2 all but 1 showed an improved renal function by 26 +/- 19% (n = 5) after initiation of felodipine therapy. In 2 cases with very low glomerular filtration rate (6 to 7 ml/min/1.73m2) the deterioration of renal function continued after felodipine, but at a slower rate. It is concluded that felodipine decreased blood pressure dramatically in patients with severe hypertension where a majority of the cases had been resistant to a previous therapy. The drug appeared safe also in advanced renal insufficiency.

Clinical evaluation of felodipine in patients with refractory hypertension.

The calcium antagonist, felodipine, was used to treat 21 patients with severe uncontrolled hypertension: 13 had renoparenchymatous hypertension, 5 essential hypertension and 3 renovascular hypertension. Mean arterial blood pressure of patients was 195 +/- 8/122 +/- 3mm Hg in spite of treatment with 3 or more antihypertensive drugs. The majority of the patients (n = 17) were treated with an ACE inhibitor. Mean glomerular filtration rate (GFR) for 20 patients was 39 +/- 6 ml/min/1.73m2 body surface area (Cr-EDTA clearance) before felodipine administration. All patients had an immediate blood pressure fall after 5-10mg of felodipine administered orally. This fall persisted when the drug was given 2 or 3 times daily in combination with previous medication except the former vasodilating drugs. 15 patients are on long term treatment with felodipine and their blood pressure after 1 year (n = 14) was 152 +/- 4/89 +/- 2mm Hg. Patients with moderately impaired renal function and no signs of progressive kidney disease (n = 8) improved their GFR significantly after 1 year on felodipine. Six patients stopped felodipine therapy within 3 months (4 because of adverse reactions, 1 died of scleroderma and 1 became normotensive after the start of dialysis treatment). In patients with renoparenchymatous disease and documented progressive deterioration of renal function the addition of felodipine did not prevent a decline in filtration rate but did slow the rate of deterioration (from 9 +/- 2 to 5 +/- 1 ml/min/year).(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of progressive renal disease in diabetes mellitus.

The prognosis for the patient with diabetic nephropathy has improved considerably during the last decade. This is due to identification and treatment of different risk factors. Elevated blood pressure has turned out to be a major risk factor in established diabetic nephropathy. The impact of metabolic control has also been demonstrated. Lipid abnormalities have recently been identified as a possible factor that accelerates loss of renal function. The role of renal hemodynamic alterations is probably also important. Their contribution can indirectly be assessed by studying the effects of pharmacologic therapy. Angiotension converting enzyme inhibitors reduce proteinuria by a mechanism independent of systemic blood pressure and there is suggestive evidence that they preserve renal function to a greater degree than other antihypertensive agents.

Long-term enalapril treatment in diabetic nephropathy.

A randomized comparison of enalapril and metoprolol in patients with type 1 diabetes and nephropathy showed that the decline in kidney function was 5.6 +/- 5.9 ml/min/year in the metoprolol-treated and 2.0 +/- 3.2 ml/min/year in the enalapril-treated patients (P = 0.02). In the present study, the enalapril treated patients have been studied for two additional years. In the metoprolol-treated group, only the endpoints of death or uremia have been recorded, and six of the patients have reached end-stage renal failure and three are dead, compared to three and two, respectively in the enalapril treated group. The mean fall in glomerular filtration rate in 18 enalapril-treated patients is 8.4 +/- 9.4 ml/min/1.73 m2 after four years; 7.5 +/- 9.8 ml/min/1.73 m2, occurred during the first six months treatment. The mean decline in kidney function was 1.7 +/- 2.4 ml/min/year over the whole study period and 0.3 +/- 3.9 ml/min/year after exclusion of the first six months. In this study, long-term enalapril treatment in diabetic nephropathy was associated with a low rate of decline in kidney function.

Substance P in the control of extrahepatic biliary motility in the cat.

The effects of regional intra-arterial injections of substance P (SP) or efferent electrical stimulation of the vagal nerves on feline extrahepatic biliary motility were studied in anesthetized cats using a constant perfusion model. Each of these procedures elicited contractile motor responses of the gallbladder and the sphincter of Oddi. Since SP is present in feline vagal axons, these findings may indicate a role of SP in the vagal motor control of biliary motility. Immunocytochemically neurons with SP-like immunoreactivity were found in the smooth muscle layers of the biliary tree as well as adjacent to acetylcholinesterase-positive ganglion cells indicating either direct activation of smooth muscle cells and/or indirect activation via cholinergic neurons. Depending on the type of stimulation different SP mechanisms were demonstrated; exogenous SP induced contraction of both the sphincter and the gallbladder which were probably direct (resistant to atropine but sensitive to a SP analogue), while vagal stimulation elicited contraction of both regions via a mechanism sensitive to atropine and to a SP analogue.

Induction of specific immunity at mucosal surfaces: prospects for vaccine development.

We have demonstrated the feasibility of studying antigen-specific immune responses in a variety of mucosal tissues in humans after vaccination and during infection. In this respect, we have documented the usefulness of both oral cholera and ETEC vaccines for assessing in functional terms specific subpopulations of B- and T-cell immunocytes during an immune response initiated and/or expressed in human mucosal tissues. Circulating specific IgA antibody-secreting cells in blood appear to reflect recent or ongoing antigen exposure of mucosal surfaces. This implies that the detection of such cells in blood, the most accessible lymphoid compartment in humans, represents the simplest way to assess the immunogenicity of mucosal vaccines and to supplement the diagnostic and monitoring of active mucosal infections. Our studies indicate that while the concept of an integrated mucosal immune network is clearly operational in humans (at least in regards to induction of secretory antibody responses), its generalization appears somewhat simplistic as illustrated by the compartmentalization of immune responses initiated in certain mucosal organs such as the small intestine and the tonsils. Finally, the potential of the cholera toxin B subunit as a carrier for delivery of chemically or genetically linked foreign epitopes for induction of disseminated mucosal immune responses raises hope for the development of broadly applicable vaccines to control mucosal infections.

Renal protective effect of enalapril in diabetic nephropathy.

OBJECTIVE: To determine whether inhibition of angiotensin converting enzyme can reduce the rate of decline in kidney function more than reducing blood pressure with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting a mean of 2.2 years in patients with diabetic nephropathy. SETTING: Three outpatient nephrology clinics. PATIENTS: 40 patients with insulin dependent diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURE: Rate of decline in glomerular filtration rate measured as chromium-51 edetic acid clearance. RESULTS: Glomerular filtration rate declined a mean of 2.0 (SD 3.2) ml/min/year in the group given enalapril and 5.6 (5.9) ml/min/year in the control group. The mean arterial blood pressure during the study was 102 (5) mm Hg in the patients given enalapril and 103 (5) mm Hg in the patients given metoprolol. Urinary albumin excretion during treatment with enalapril was 60% lower than during treatment with metoprolol. CONCLUSIONS: Enalapril has an antiproteinuric effect independent of the effect on systemic blood pressure. Treatment with enalapril can reduce the rate of decline in kidney function in patients with diabetic nephropathy more than equally effective antihypertensive treatment with metoprolol. This points to a specific renal protective effect of angiotensin converting enzyme inhibitors in diabetic nephropathy.

Contrasting effects of enalapril and metoprolol on proteinuria in diabetic nephropathy.

OBJECTIVE: To assess whether angiotensin converting enzyme inhibition reduces proteinuria in diabetic nephropathy more than blood pressure reduction with other antihypertensive treatment. DESIGN: Prospective, open randomised study lasting eight weeks in patients with diabetic nephropathy. SETTING: Outpatient nephrology clinics. PATIENTS: 40 Patients with type I diabetes and diabetic nephropathy with reduced renal function. INTERVENTION: Antihypertensive treatment with enalapril or metoprolol, usually combined with frusemide. MAIN OUTCOME MEASURES: Arterial blood pressure and urinary excretion of albumin and protein. RESULTS: Arterial blood pressure after eight weeks was 135/82 (SD 13/7) mm Hg in the group given enalapril and 136/86 (16/12) mm Hg in the group given metoprolol. Proteinuria and albuminuria were similar in both groups before randomisation. After eight weeks' treatment, the geometric mean albumin excretion was 0.7 (95% confidence interval 0.5 to 1.2) g/24 h in the patients given enalapril and 1.6 (1.1 to 2.5) g/24 h in the patients given metoprolol (p less than 0.02). The proteinuria was 1.1 (0.7 to 1.7) and 2.4 (1.6 to 3.6) g/24 h respectively (p less than 0.02). CONCLUSIONS: Antihypertensive treatment with enalapril reduced proteinuria in patients with diabetic nephropathy more than an equally effective antihypertensive treatment with metoprolol. This points to a specific antiproteinuric effect of the angiotensin converting enzyme inhibitor independent of the effect on systemic blood pressure.

[Early treatment can improve prognosis in diabetic nephropathy]. / Tidig behandling kan förbättra prognos vid diabetisk njursjukdom.

Prognosis in diabetic nephropathy has changed dramatically during the past decade, and slowing of the disease process has been made possible by intervention against specific risk factors. Nonetheless, diabetic nephropathy has become the leading cause of end stage renal disease. Early detection and prevention, or at least delaying, of disease progression have become crucial aims, and several treatment strategies designed to prevent end stage renal disease have recently been published. The common denominator of these strategies is screening for microalbuminuria in diabetic patients rather than awaiting the appearance of overt symptoms.

The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study.

The purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one-fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone.

Renin secretion in advanced diabetic nephropathy.

Low basal and stimulated plasma renin activity (PRA) levels have been reported in patients with diabetic nephropathy (DN). We have measured PRA before and after stimulation with captopril in 28 patients with DN and in 25 control patients. Renal function impairment was similar in both groups. Most patients were treated with furosemide. In 19 patients with DN the PRA-response to dihydralazine was also studied. PRA before and after captopril were higher in the DN than in the control group (p less than 0.001). PRA increased from 4.6 +/- 3.6 to 6.3 +/- 5.3 in the DN, and from 1.8 +/- 2.7 to 2.7 +/- 3.4 in the control patients. The increases in PRA, caused by decreased angiotensin II feed-back inhibition, were comparable. PRA did not increase after dihydralazine despite a pronounced blood-pressure reduction. The difference in response to these stimuli indicate selective lesions involving both the sympathetic innervation and the renal baroreceptor function in DN. Overhydration is a plausible explanation to the low PRA earlier reported in DN. The results thus indicate that a preserved renin secretion capacity is present in DN. Differences in PRA between the both groups can only partly be explained by other factors than DN. Our findings indicate a role for the reninangiotensin-system in hypertension in DN.

Inguinal hernia repair using a synthetic long-term resorbable mesh: results from a 3-year prospective safety and performance study.

PURPOSE: Conventional meshes for hernia repair and abdominal wall reinforcement are usually made from polypropylene, polyester or other synthetic plastic materials known to promote foreign body reactions and a state of chronic inflammation that may lead to long-term complications. A novel approach is to use long-term resorbable implants like TIGR(®) Matrix Surgical Mesh. Preclinical studies have shown that this mesh maintains mechanical integrity beyond the point in time where newly formed tissue is capable of carrying the abdominal loads. METHODS: This was a first-in-man, prospective, pilot study performed during 2009, at two sites in Sweden. Forty patients with primary inguinal hernias were enrolled for Lichtenstein repair using TIGR(®) Matrix Surgical Mesh. The primary endpoint was safety as assessed by monitoring the incidence of adverse events and serious adverse events (SAEs) both related and unrelated to the mesh. The secondary endpoint was pain or discomfort. Visual Analogue Scale (VAS) 0-10 and Inguinal Pain Questionnaire were used for scoring pain and discomfort. Included patients have been followed for 36 months using ultrasound in combination with clinical examination. RESULTS: All patients followed a normal early postoperative course. After 12 months no SAEs were reported. None of the patients with an isolated lateral inguinal hernia (LIH) had developed a recurrence but 4 (44 %) with medial and 4 (33 %) with combined hernias had recurred at 36-month follow-up. After 3-year follow-up none of the patients with LIH reported pain in the VAS-form and none of those patients could feel the sensation of a mesh in their groin. In the total study population 5 (16 %) patients experienced chronic pain in the form of mild sporadic pain and 3 (9.7 %) patients could feel the sensation of a mesh in their groin. CONCLUSION: The use of a synthetic long-term resorbable mesh (TIGR(®) Matrix Surgical Mesh) in Lichtenstein repair was found to be safe, without recurrences, and promising regarding pain/discomfort at 3-year follow-up in patients with LIH. However, patients with medial and combined inguinal hernias had high recurrence rates.