[Medication reconciliation at hospital discharge focusing on patient with hypertension: Analysis of the output prescription]. / Conciliation médicamenteuse à la sortie d'hospitalisation du patient hypertendu : analyse de l'ordonnance de sortie.

PURPOSE: To describe pharmacists' interventions made at patients hospital discharge from Department of Hypertension. METHODS: This is a single-center and prospective study over an 8-week period. At hospital discharge, the pharmacist compared pre-admission and inpatient medications with discharge orders and written instructions. Pharmacists' interventions were then classified in 4 categories. All variances and discrepancies were discussed with the prescribing physician when possible. RESULTS: Over the 8-week period, 154 cases were analyzed. Pharmacists' interventions at discharge underwent 48 times on 21% of the patients (n=33) but none was clinically relevant. Among these 48 cases, 40% (n=19) were rated as "inappropriate administration", 27% (n=13) were classified as "incomplete prescription", 19% (n=9) were "variances" and 4% (n=2) were due to "omission prescription". In 10% of the cases (n=5), discrepancies appeared without any possible further analysis as no discussion with the prescriber occurred. CONCLUSION: One fifth of all patients analyzed was the subject of a pharmacists' intervention. The complementary action of the pharmacist improves the consistency of the prescriptions and strengthens patient safety.

Causes of secondary hypertension in the young population: A monocentric study.

OBJECTIVE: To study the prevalence of different causes of hypertension in young adults referred to a hypertension center in the south west of France. METHODS: We conducted a retrospective overview of patients younger than 40years old hospitalized consecutively in the Hypertension department of Toulouse University Hospital between 2012 and 2014. Clinical data about gender, age, anthropomorphic parameters and blood pressure measurement by 24h Ambulatory Blood Pressure Monitoring (ABPM) were recorded. Biological data concerned dosages of kalemia, renin and aldosterone in the supine or after 15min of seating. Recorded radiological examinations were renal artery ultrasound and abdominal CT scan. RESULTS: One hundred and forty-eight detailed medical records were analyzed, 69 women and 79 men. Among the 69 women, the causes of secondary hypertension were primary aldosteronism (n=7), fibromuscular dysplasia (n=5) and renal disease (n=4). Oral contraceptives were involved in 13 women. In addition, essential hypertension concerned 40 women (58%). Among the 79 men, the causes of secondary hypertension were primary aldosteronism (n=10), fibromuscular dysplasia (n=3), left main renal artery entrapment by a diaphragmatic crura (n=2), renal disease (n=1), pheochromocytoma (n=3) and coarctation of the aorta (n=2). In addition, essential hypertension concerned 58 men (73%). CONCLUSIONS: In our population, the prevalence of secondary hypertension is close to 33% (42% of females and 27% of males), with the following main causes: primary aldosteronism for 11.5%; fibromuscular dysplasia for 5.4%. Oral contraceptives were involved in the hypertension of 19% of the females.

Lactic acidosis: relationship between metformin levels, lactate concentration and mortality.

AIM: The role of metformin in lactic acidosis is regularly questioned. Arguments against a causal role for metformin in lactic acidosis occurrence are the lack of correlation between plasma metformin and lactate levels, as well as between metformin plasma levels and mortality. We aim to analyse these correlations in a large series of lactic acidosis cases recorded in the French nationwide pharmacovigilance database. METHODS: All cases of lactic acidosis spontaneously reported between 1985 and October 2013 associated with metformin exposure were extracted from the pharmacovigilance database. We assessed the statistical correlations between prescribed daily doses of metformin, plasma concentrations of metformin and lactate, pH and plasma creatinine, as well as the relationship between mortality and these variables. RESULTS: Seven hundred and twenty-seven cases of lactic acidosis were reported during the period. Metformin plasma concentration was documented for 260 patients, lactate plasma concentration for 556 patients, pH for 502 patients, creatinine for 397 patients and the vital outcome for 713 patients. Metformin plasma concentration, lactate concentration, pH and plasma creatinine were all correlated (P < 0.001). There were significant differences between surviving and deceased patients in terms of metformin plasma levels (25.2 vs. 37.4 mg/l, P = 0.002) and lactate concentrations (10.8 vs. 16.3 mmol/l, P < 0.001). Thirty per cent of patients died when metformin concentration was > 5 mg/l compared with 11% for patients with concentration < 5 mg/l (P = 0.003). CONCLUSIONS: Our data suggest that metformin accumulation contributes to the pathogenesis and prognosis of lactic acidosis.

Urinary and genital infections in patients with diabetes: How to diagnose and how to treat.

Diabetes is a predisposing factor for urinary tract and genital infections in both women and men. Sodium-glucose cotransporter-2 (SGLT2) inhibitors constitute a novel therapeutic class indicated for type 2 diabetes (T2D) patients, and are already on the market in a few countries in Europe. They decrease glycaemia mainly by enhancing glucose excretion in urine by reducing renal glucose reabsorption via the action of SGLT2 in the kidneys. In general, they are well tolerated, but their mode of action results in specific side effects as well as an increased risk of genital (vulvovaginitis and balanitis) and urinary tract infections, for which T2D patients are already at high risk, reported within the first 6 months of treatment. Usually these infectious events are successfully treated with standard therapies, but diabetologists are not accustomed to dealing with them. The aim of this review is to describe the different types of lower urinary tract and genital infections, and the treatment strategies currently available for patients with diabetes.

[Place of clinical pharmacist in the management of drugs in patients with hypertension]. / Place du pharmacien clinicien dans la prise en charge thérapeutique du patient hypertendu.

PURPOSE: To synthesize pharmacists' interventions made in the department of internal medicine and hypertension of university hospital of Toulouse and assess the impact on medication orders. METHODS: This is a single-center, prospective study using pharmacists' interventions recorded between September 2013 and March 2014 on the Act-IP(©) website of the French Society of Clinical Pharmacy. The clinical pharmacist is present everyday in the unit to establish the medication reconciliation of new patients (the process of comparing a patient's medication orders to all of the medications that the patient has been taking), and analysis of medication orders. When a risk of iatrogenic drug is identified, a therapeutic change is proposed to the prescriber. RESULTS: A total of 2491 medication orders were analyzed for 7 months, leading to 39 pharmacists' interventions (1.6 pharmacists' interventions per 100 medication orders). The most commonly identified drug-related problems were improper administration (33%, n=13), not prescribed drug (21%, n=8), non-conformity to guidelines (18%, n=7), supratherapeutic dose (15%, n=6), and 13% (n=5) targeted prescribed treatment not administered, underdosing, incorrect administration or drug interaction. The most relevant molecules were atorvastatin (10%), bromazepam (8%) and levothyroxine (8%) and only 2 interventions targeted antihypertensive drugs. The rate of physicians' acceptance was 92%. CONCLUSION: Pharmacists' interventions mainly concern the co-prescriptions of antihypertensive drugs and very few antihypertensive drugs. The clinical pharmacist contributes to preventing iatrogenic in patients with hypertension with a very good acceptance by the clinician.

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension.

AIMS: To study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening. METHODS: Fifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 µUI/mL. RESULTS: Referring to ARR cut-off of 23 pg/µUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P<0.001). CONCLUSIONS: Current recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/µUI increased the discriminating power of this test.

Orthostatic hypotension is associated with more severe hypertension in elderly autonomous diabetic patients from the French Gerodiab study at inclusion.

UNLABELLED: Orthostatic hypotension (OH) has deleterious effects on patients' cardiovascular prognoses. The combination of increased age and diabetes adds to the risk of OH. The aim of the study was to describe the elderly diabetic population relative to the degree of hypertension, the occurrence of complications, medications and cognitive function. METHODS: In the Gerodiab study (a 5-year French multicentre, prospective, observational study), a total of 987 type 2 diabetic autonomous patients, aged 77±5 years, were recruited between June 2009 and July 2010. Clinical blood pressure measurements were taken supine and then after 1, 3 and 5minutes in a standing position. OH was defined as a decrease in systolic blood pressure (SBP) of at least 20mmHg and/or a decrease in diastolic blood pressure (DBP) of at least 10mmHg at any of the measurements while standing. RESULTS: At inclusion 301 (30.5%) patients had OH; SBP and DBP at rest were higher in patients with OH than in those without (146±21/78±11mmHg vs. 138±17/72±10mmHg; P<0.001). Individuals with OH exhibited higher pulse pressure (PP) than individuals without (68±18 vs. 65±15mmHg; P<0.05). A significant increase in waist-to-hip ratio was recorded in those with OH versus patients without (P<0.01). Despite more severe hypertension (SBP>160mmHg at inclusion; P<0.01), no significant difference was recorded in the mean number of antihypertensive drugs (1.7±1.1), or in the class of antihypertensive drugs, including beta-blockers (P=0.19) and diuretics (P=0.84). Patients with OH were more likely to have a history of peripheral arterial disease and amputations (31% vs. 24%, P<0.05, and 3.3% vs. 1.5%, P=0.056). There was no significant association between OH and history of peripheral neuropathy (P=0.37), stroke, heart failure or ischemic heart disease. In multivariate analysis, OH remained associated with severe hypertension (P<0.01), increased waist-to-hip ratio (P<0.05) and amputations (P<0.05). CONCLUSION: About one-third of elderly, autonomous diabetic patients had OH. They had more severe hypertension, with higher SBP, DBP and PP at rest. However, the number of anti-hypertensive drugs did not differ compared to patients without OH. This could reflect the medical teams' fears about intensifying treatment.

Is it useful to repeat an adrenal venous sampling in patients with primary hyperaldosteronism?

UNLABELLED: Adrenal venous sampling (AVS) is a challenging technical procedure and few patients had AVS procedure twice. AIM: To evaluate the reproducibility of the AVS, why AVS were repeated and the conclusions drawn from them. PATIENTS AND METHODS: From 1997-2012, 12 patients underwent two AVS. A cortisol level in the adrenal vein greater than or equal to 1.1 to inferior vena cava defined a successful catheterization and a lateralization of secretion corresponded to an aldosterone-to-cortisol vein ratio greater than or equal to 2 between the one side to another. RESULTS: The same side of lateralization of secretion was found in 75% of them. The second AVS were due to technical failure (n=4), unproven lateralization (n=2), a lateralization opposite to the main nodule and ipsilateral to hyperplasia (n=4) on first AVS. For two patients, as the CT was normal, AVS was required again. The second AVS was successful in all patients, including those with an initial technical failure but only patient with technical failure underwent surgery, as BP and kaliemia were controlled. Lateralization on the side of hyperplasia or opposite to the biggest nodule was confirmed in two of four cases. CONCLUSION: When AVS is unsuccessful for technical reasons, it is worth doing it again but after being sure that surgery is still possibly indicated.

Clinical and metabolic characteristics of patients with latent autoimmune diabetes in adults (LADA): absence of rapid beta-cell loss in patients with tight metabolic control.

AIM AND METHODS: The present study compared the clinical and metabolic characteristics of latent autoimmune diabetes in adults (LADA) with type 2 diabetes, as well as the residual beta-cell function and progression to insulin treatment, over a 2-year follow-up period, of antibody (Ab)-positive and Ab-negative patients who achieved tight glycaemic control (HbA(1c) 7.0+/-0.8% and 6.5+/-0.9%, respectively, at the time of entry into the study). RESULTS: Glutamic acid decarboxylase antibodies (GADA) and/or islet cell antibodies (ICA) were detected in 10% of patients presenting with non-insulin-dependent diabetes. Around half of Ab-positive patients required insulin treatment during the follow-up. Ab-positive patients displayed lower stimulated C-peptide levels both at entry and during the follow-up compared with Ab-negative patients, although no significant decline in C-peptide levels was observed in either subgroup over two years. Nevertheless, Ab-positive patients progressed more frequently to insulin treatment, and stimulated C-peptide tended to decrease in LADA patients who subsequently required insulin, whereas it remained stable in those who were non-insulin-dependent. In those who progressed, the trend towards C-peptide decline persisted even after starting insulin treatment. CONCLUSION: LADA patients demonstrate lower residual beta-cell function than do type 2 diabetes patients. However, those who achieve tight metabolic control do not present with a rapid decline in beta-cell function. Further studies are needed to determine the optimal treatment strategy in such patients.

The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes.

CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Prognostic value of nocturnal blood pressure and reverse-dipping status on the occurrence of cardiovascular events in hypertensive diabetic patients.

AIM: To assess whether reverse-dipping status is associated with cardiovascular (CV) events such as CV death, myocardial infarction (MI) or stroke in diabetic patients with hypertension. METHODS: A total of 97 diabetic patients underwent their first ambulatory blood pressure monitoring (ABPM 1). "Reverse dippers" were defined as patients with a nighttime systolic and/or diastolic blood pressure (BP) greater than daytime systolic and/or diastolic BP. Other patients were called "others". A second ABPM (ABPM 2) was done after a median delay of 2.6 years. Patients were then followed for a further 2.9-year median period (total median follow-up: 5.5 years). RESULTS: After ABPM 1, CV events occurred in 53% of the reverse dippers (n=15) and in 29% of the others (n=82). Kaplan-Meier curves showed significant differences between the two groups (P=0.003). Mean nighttime systolic BP on ABPM 1 was 148+/-23 mmHg and 142+/-19 mmHg in patients who did and did not experience a CV event, respectively. With Cox analysis adjusted for confounders, a 10 mmHg increase in nighttime systolic BP was associated with a 35% increase in the risk of a CV event (hazard ratio [HR]: 1.35, P=0.003). The HR for a CV event in reverse- versus nonreverse-dipping status was 2.79 (P=0.023). After ABPM 2, the relationship between the reverse-dipping status and occurrence of CV events was no longer evident (P=0.678). Nighttime systolic BP remained predictive of CV events (P=0.001). CONCLUSION: These findings suggest that nighttime systolic BP per se appeared to be a stronger predictor of an excess risk of CV events compared with reverse-dipping status.

Retinal and renal complications in patients with a mutation of mitochondrial DNA at position 3,243 (maternally inherited diabetes and deafness). A case-control study.

AIMS/HYPOTHESIS: We assessed the prevalence and determinants of retinal and renal complications in patients with maternally inherited diabetes and deafness (MIDD). METHODS: This was a multicentre prospective study comparing the prevalence of retinopathy and renal disease in 74 patients with MIDD and 134 control patients matched for sex, age and clinical presentation at onset of diabetes, duration of diabetes and current treatment. Comparisons were adjusted for HbA(1c) and hypertension. RESULTS: In MIDD patients, HbA(1c) (7.6 +/- 1.6 vs 8.5 +/- 2.0%, p < 0.002), systolic blood pressure (126.6 +/- 16.2 vs 133.1 +/- 17.3 mmHg, p < 0.007) and prevalence of hypertension (33.8 vs 64.2%, p < 0.0001) were lower than in control patients. Prevalence of diabetic retinopathy was 3.7-fold lower in MIDD patients (6/74, 8 vs 40/134, 29.6%, p < 0.0001). Differences between groups remained significant after adjustment for hypertension, systolic blood pressure and HbA(1c). In MIDD, urinary albumin excretion (314.8 vs 80.1 mg/24 h, p = 0.035) and creatinine plasma levels (103.5 vs 82.2 micromol/l, p = 0.0178) were higher and GFR was lower. Impaired renal function (GFR <60 ml/min) was four- to sixfold more frequent in MIDD. Differences between MIDD and control diabetic patients further increased when adjusted for HbA(1c) and systolic blood pressure (p < 0.0001). Adjustment for treatment with an ACE inhibitor or angiotensin II receptor antagonist did not modify the results. CONCLUSIONS/INTERPRETATION: This study indicates that diabetic retinopathy is less prevalent in MIDD than in control diabetes. This suggests that retinal alterations due to mitochondrial disease may have a protective role. By contrast, nephropathy is far more frequent in MIDD, suggesting the presence of a specific renal disease independent of diabetic nephropathy.

Should pulse pressure and day/night variations in blood pressure be seen as independent risk factors requiring correction or simply as markers to be taken into account when evaluating overall vascular risk?

Patients with a blunted fall in nocturnal BP (known as non-dippers) have a high risk of micro- and macrovascular complications, particularly if they have hypertension, but also in normotensive patients with diabetes. A blunted fall in nocturnal BP reflects the high level of CV risk in these patients. ABPM data indicating an altered circadian BP rhythm reverse circadian BP profile should alert the physician to the potential risk of complications and should lead to efforts to treat hypertension effectively, especially at night, and to check for sleep apnoea syndrome, particularly in cases of resistant hypertension, or autonomic neuropathy (postural hypotension), a well known risk factor for cardiovascular (CV) events. Patients should be carefully screened for nephropathy. However, the definitions of "non-dipper" vary widely. Suitable treatments are poorly defined, but angiotensin-converting enzyme inhibitors (ACEi), diuretics, salt restriction and the maintenance of continuous positive airway pressure (CPAP) can be used as non-specific treatments. The efficacy of taking blood pressure-lowering drugs at bedtime rather than in the morning is still debated but deserves attention. In the diabetic population, brachial pulse pressure (PP) is an independent predictor of cardiovascular mortality, but not of all-cause mortality. It is also associated with complications of both type 2 and type 1 diabetes, this effect being stronger for nocturnal than for diurnal PP, and is strongly predictive of coronary heart disease in patients with type 2 diabetes. The stronger association between PP and age in diabetic than in non-diabetic populations suggests that diabetes accelerates vascular ageing. In patients with incipient nephropathy or overt renal failure, PP increases CV risk. However, misinterpretation could be related to confusion between brachial PP and central PP. The therapeutic implications of PP measurement remain poorly documented in diabetes.

Characteristics and six-month outcomes in a cohort of 8288 diabetic and non-diabetic patients with previous history of acute coronary syndrome or stroke: the French PREVENIR 3 survey.

AIMS: To evaluate the cardiovascular prognosis of 1845 Diabetic Patients (DP) and 6443 Non-Diabetic Patients (NDP) in secondary prevention. METHODS: Patients were recruited prospectively if they had had a previous history of ischemic stroke or acute coronary syndrome (ACS) i.e. Myocardial Infarction (MI) or Unstable Angina (UA) within a period of five years preceding inclusion. For each patient, the number of hospitalizations and vital status were recorded each month over a 6-month period (mean follow-up: 4.8 months). RESULTS: 306 patients (9.5/100--person years; 95% CI, 8.5 to 10.6) had undergone at least one subsequent event (hospitalization for ACS, ischemic stroke, or cardiovascular death). A majority of these events were non-fatal ACS (n=248). The cumulative incidence rate of subsequent events was higher in DP: 12.6/100- person years (10.0 to 15.2) than in NDP: 8.6/100--person years (7.5 to 9.8). DP were significantly at higher risk of subsequent cardiovascular events (OR: 1.34; P=0.025) after adjustment for confounding factors. 93% of coronary DP and NDP underwent a recurrent event affecting the same location. When the index episode was a stroke, 71% of DP had a subsequent stroke vs. 47% of NDP. CONCLUSION: in secondary prevention, the risk of mortality and subsequent vascular events is independently higher in French DP than in NDP. The locations affected by each type of subsequent cardiovascular event seemed correlated to the baseline diagnosis, whatever the diabetic status, even when the frequency of subsequent strokes increased (not significantly) in DP when compared to NDP.

'Glucose control-related' and 'non-glucose control-related' effects of insulin on weight gain in newly insulin-treated type 2 diabetic patients.

Insulin use is common in type 2 diabetes and is frequently accompanied by weight gain, the composition of which is poorly understood. The present study evaluates insulin-induced body composition changes. Body weight and composition of thirty-two type 2 diabetic patients undergoing their first 12 months of insulin therapy were compared with those observed in thirty-two type 2 diabetic patients previously treated on insulin (minimum 1 year). Body composition was determined by simultaneous body water spaces (bioelectrical impedance analysis) and body density measurements. After 6 months, glycosylated Hb (HbA1c) significantly improved in the newly treated group (P<0.0001), but remained stable in those treated previously. HbA1c did not differ between 6 and 12 months in the two groups. Body weight significantly (P=0.04) changed over 12 months in those newly treated only (+2.8 kg), essentially comprising fat-free mass (P=0.044). Fat mass remained unchanged (P=0.85) as did total body water, while extracellular: total body water ratio tended to increase in those newly treated (P=0.059). Weight changes correlated with HbA1c changes (R2 0.134, P=0.002) in the initial 6 months only. Insulin therapy leads to weight gain (2.8 kg), predominantly fat-free mass, over 12 months. After 6 months, newly treated patients continued gaining weight despite an unchanged HbA1c, suggesting the potential anabolic role of insulin in subsequent gains. Therefore, in the initial 6 months, weight gain can be attributed to a 'glucose control-related effect' and further gain appears to be due to a 'non-glucose control-related' effect of insulin treatment.