Reasons for non-intensification of treatment in people with type 2 diabetes receiving oral monotherapy: Outcomes from the prospective DIAttitude study.

OBJECTIVES: To describe the management of glucose-lowering agents in people with type 2 diabetes initially on oral monotherapy, cared for by French general practitioners, and to identify reasons underlying treatment non-intensification. METHODS: People with type 2 diabetes on oral monotherapy were recruited by general practitioners and followed-up over 12 months. Patient characteristics, HbA1c, and glucose-lowering treatments were recorded electronically. Management objectives and reasons for treatment non-intensification were solicited from the general practitioners. RESULTS: A total of 1212 patients were enrolled by 198 general practitioners; 937 patients (mean age 68 years) were treated with oral monotherapy, and 916 patients had at least two successive HbA1c values recorded. Of these, 390 patients (43%) had HbA1c≥6.5% on both occasions, and 164/390 (42%) had their treatment intensified. The 226 patients whose treatment was not intensified were older (69±11 years vs. 66±12 years, P=0.02) and had better glycaemic control at study inclusion (6.9%±0.6 vs. 7.3%±0.8, P<0.0001) than treatment intensified patients. Among uncontrolled patients, there were no differences in general practitioner treatment objectives at inclusion for treatment intensified and non-intensified patients; the main reason given by general practitioners for non-intensification was that the patient had an adequate HbA1c (66%). HbA1c did exceed the 6.5% target, but was less than 7.0% in 69% of cases. CONCLUSIONS: General practitioners showed a patient-centred approach to treatment, but clinical inertia was apparent for 31% of the uncontrolled patients.

Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment.

PURPOSE: Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences. SUBJECTS AND METHODS: We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency. RESULTS: The median patient age was 76 +/- 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (+/- standard deviation) of 131 +/- 38 pg/mL and total serum homocysteine level of 22.1 +/- 9.3 micromol/L. The mean hemoglobin level was 10.9 +/- 2.5 g/dL and the mean erythrocyte cell volume 95.7 +/- 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSIONS: This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy.

Effects of oral crystalline cyanocobalamin 1000 µg/d in the treatment of pernicious anemia: An open-label, prospective study in Ten Patients.

BACKGROUND: Standard treatment of cobalamin (vitamin B12) deficiency involvesregular (1000 µg/mo) IM cyanocobalamin administration. It has been suggested that high-dose (>2000 µg/d) oral cyanocobalamin may be effective in patients with pernicious anemia. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of oral crystalline cyanocobalamin 1000 µg/d in patients with cobalamin deficiency related to established pernicious anemia. METHODS: This open-label, prospective study was conducted at StrasbourgUniversity Hospital, Strasbourg, France. Patients aged ≥18 years with well-documented cobalamin deficiency related to pernicious anemia were enrolled. Patients received crystalline cyanocobalamin 1000 µg QD PO (capsule) for at least 3 months. Serum cobalamin, folate, iron, and homocysteine concentrations were measured, and a complete blood count was obtained, before (month 0; baseline) and after treatment. RESULTS: Ten patients (7 women, 3 men; mean [SD] age, 72.1 [15.5] years) entered the study. After 3 months of treatment, serum cobalamin concentration increased in all 9 patients in whom it was measured (mean [SD] increase, 117.4 [30.8] pg/mL; P < 0.001 vs baseline). Serum cobalamin concentrations were normalized (>200 pg/mL) in 6 patients. The serum cobalamin concentration was unavailable in 1 patient because of technical problems. Eight patients had increased hemoglobin concentrations (mean [SD] increase, 2.5 [2.4] g/dL; P < 0.01 vs baseline). All 10 patients had decreased mean erythrocyte corpuscular volumes (mean [SD] decrease, 10.4 [6.2] fL; P < 0.003 vs baseline). Four patients received concomitant blood transfusions or folate and iron supplementation. Three patients experienced clinical improvement in paresthesia, reflex abolition, or combined medullary sclerosis (each, 1 patient). CONCLUSION: The results of this small study in patients with cobalamin deficiencyrelated to pernicious anemia suggest that oral crystalline cyanocobalamin 1000 µg/d may be an effective treatment.

[Recurrent facial palsy, primary Gougerot-Sjögren's syndrome and vitamin B12 deficiency]. / Paralysie faciale récidivante, syndrome de Gougerot-Sjögren primitif et carence en vitamine B12.

INTRODUCTION: Differing cranial nerve involvement has been reported in the context of Gougerot-Sjögren's syndrome. Involvement of the V, III and VII nerves has been reported, the most characteristic being nerve V, notably its lower branch. Rare, well documented, cases of facial palsy have also been described. OBSERVATION: Recurrent facial palsy in a 40 year-old woman revealed a primary Sjögren's syndrome and vitamin B12 deficiency. DISCUSSION: The onset of facial palsy has been linked with Gougerot-Sjögren's syndrome. The contribution of vitamin B12 deficiency is discussed.

Potential glycemic overtreatment in patients ≥75 years with type 2 diabetes mellitus and renal disease: experience from the observational OREDIA study.

BACKGROUND: Few data exist examining the management of elderly patients with type 2 diabetes mellitus and renal impairment (RI). This observational study assessed the therapeutic management of this fragile population. METHODS: Cross-sectional study: data from 980 diabetic patients ≥75 years with renal disease are presented. RESULTS: Patients had a mean age of 81 years (range 75-101) with long-standing diabetes (15.4 years) often complicated (half with macrovascular disease). Mean estimated glomerular filtration rate was 43 mL/min/1.73 m(2) and 20% had severe RI. Mean hemoglobin A1c was 7.4%. Anti-diabetic therapy was oral based for 51% of patients (60% ≥2 oral anti-diabetic drugs [OAD]) and insulin based for 49% (combined with OAD in 59%). OAD included metformin (47%), sulfonylureas (26%), glinides (19%), and DPP-4 inhibitors (31%). Treatments were adjusted to increasing RI, with less use of metformin, sulfonylureas, and DPP-4 inhibitors, and more glinides and insulin in severe RI. In all, 579 (60%) of these elderly patients with comorbidities had hemoglobin A1c <7.5% (mean 6.7%) while being intensively treated: 69% under insulin-secretagogues and/or insulin, putting them at high risk for severe hypoglycemia. Only one-fourth were under oral monotherapy. CONCLUSION: In clinical practice, a substantial proportion of elderly patients may be overtreated. RI is insufficiently taken into account when prescribing OAD.

Retrospective monocentric study of 17 patients with adult Still's disease, with special focus on liver abnormalities.

BACKGROUND/AIMS: Adult Still's disease is one of the febrile disorders of unknown etiology, characterized by high fever, transient cutaneous rash and leukocytosis. Liver dysfunction in adult Still's disease has been described in some case reports. The objective of this study was to analyze the pattern and the frequency of liver abnormalities in a monocenter series of adult Still's disease patients. METHODOLOGY: Data of 17 patients with adult Still's disease (fulfilling Yamaguchi's diagnostic criteria) were retrospectively reviewed. These patients were followed in an Internal Medicine Department over a period of 7 years. RESULTS: The median age was 27 years with a sex ratio M/F of 1.4. Fever was present in 100% of the cases and hepatomegaly occurred in 47% of the cases. Abnormalities in liver biochemistry, apparent in 76% of the subjects were characterized from moderate (elevation of transaminases between 2 and 5 N) (65%) to severe cytolysis (level of transaminases > 5 N) (12%), cholestasis (elevation of gamma GT and/or PAL) (65%), and increase in the level of LDH (35%). All of these symptoms disappeared either spontaneously or under treatment (83%), within a median period of 18 days. CONCLUSIONS: This study confirms the high frequency of liver dysfunction in adult Still's disease patients. Although it is moderate and asymptomatic in most cases, severe cytolytic hepatitis has been described. This study especially puts forward the need for exploring the possibility of adult Still's disease in the presence of a fever and hepatic cytolysis.

[The place of thiazolidinediones in the treatment of type 2 diabetes]. / Place des thiazolidinediones dans le traitement du diabète de type 2.

SUPPLEMENTARY ORAL ANTIDIABETICS: Thiazolidinediones or glitazones are a new class of oral antidiabetics, the effects on blood sugar control of which are mediated by the sensitivity of the peripheral tissue to the effect of insulin. Hence, their effect is complementary to that of the insulin secreting agents and that of metformin, which acts by blocking the hepatic production of glucose. OTHER BENEFICIAL EFFECTS: Other than their effect on blood glucose, thiazolidinediones have a favorable influence upon the cardiovascular risk factors or markers such as blood pressure, C-reactive protein and metalloproteinase-9. They also appear to induce long term preservation of the beta-cell capital. Principle side effects are salt-water retention with a risk of decompensation of a pre-existing heart failure and weight gain with regard to the subcutaneous adipose tissue, without deleterious effects on blood glucose control.

[Prescribing insulin in type 2 diabetes]. / Prescrire l'insuline dans le diabète de type 2.

Insulintherapy is often the only way to obtain satisfactory glycaemic control in type 2 diabetic patients after several years of evolution of the disease. However, independently of the reluctance of the patient, it poses a few specific problems, and particularly that of weight gain initiating a vicious circle leading to deterioration of the metabolic control and to a progressive increase of insulin doses. Specific therapeutic protocols combining oral drugs and insulin have been promoted, but their efficacy is generally limited in course of time, and change to conventional or even intensified insulintherapy is in that case required. The practitioner will have to overcome his fear of using high insulin doses and give to therapeutic education the right place in order to guarantee the long term success of insulintherapy and so an effective prevention of diabetic complications.

[History of the rhenish and alsacian contributions to the understanding of diabetes]. / Histoire des contributions rhénanes et alsaciennes à la compréhension du diabète.

The history of diabetes mellitus is punctuated from the Egyptian Antiquity by sometimes amazingly acute clinical observations and inversely several missed opportunities on the way of the discovery of the mechanisms of the disease and of the development of its therapies.Alsace, and more generally the Rhine countries, have played a major role in this adventure, of which a crucial step has been the experimental demonstration of the role of the pancrease in the pathogenis of the disease by Oskar Minkowski and Joseph von Mering in Strasbourg in 1889.

How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study.

BACKGROUND AND AIM: Chronic kidney disease (CKD) is frequent in type 2 diabetes mellitus (T2DM), and therapeutic management of diabetes is more challenging in patients with renal impairment (RI). The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label. This study aimed to assess the therapeutic management, in particular the use of metformin, of T2DM patients with CKD in real life. METHODS: This was a French cross-sectional observational study: 3,704 patients with T2DM diagnosed for over 1 year and pharmacologically treated were recruited in two cohorts (two-thirds were considered to have renal disease [CKD patients] and one-third were not [non-CKD patients]) by 968 physicians (81% general practitioners) in 2012. RESULTS: CKD versus non-CKD patients were significantly older with longer diabetes history, more diabetic complications, and less strict glycemic control (mean glycated hemoglobin [HbA(1c)] 7.5% versus 7.1%; 25% of CKD patients had HbA1c ≥8% versus 15% of non-CKD patients). Fifteen percent of CKD patients had severe RI, and 66% moderate RI. Therapeutic management of T2DM was clearly distinct in CKD, with less use of metformin (62% versus 86%) but at similar mean daily doses (~2 g/d). Of patients with severe RI, 33% were still treated with metformin, at similar doses. For other oral anti-diabetics, a distinct pattern of use was seen across renal function (RF): use of sulfonylureas (32%, 31%, and 20% in normal RF, moderate RI, and severe RI, respectively) and DPP4-i (dipeptidyl peptidase-4 inhibitors) (41%, 36%, and 25%, respectively) decreased with RF, while that of glinides increased (8%, 14%, and 18%, respectively). CKD patients were more frequently treated with insulin (40% versus 16% of non-CKD patients), and use of insulin increased with deterioration of RF (19%, 39%, and 61% of patients with normal RF, moderate RI, and severe RI, respectively). Treatment was modified at the end of the study-visit in 34% of CKD patients, primarily to stop or reduce metformin. However, metformin was stopped in only 40% of the severe RI patients. CONCLUSION: Despite a fairly good detection of CKD in patients with T2DM, RI was insufficiently taken into account for adjusting anti-diabetic treatment.

Potential clinical impact of medication discrepancies at hospital admission.

BACKGROUND: Medication errors at the interfaces of care are highly prevalent. This study aims to identify unintentional medication discrepancies at hospital admission and to explore their potential clinical impact in elderly patients. METHOD: The study was conducted in an Internal Medicine Department. Patients ≥ 65 years admitted through the emergency department were eligible. Best possible medication histories, obtained from different sources by pharmacists, were compared to admission medication prescriptions to identify and correct unintentional discrepancies. A three-category scale was used to rate errors for their potential to cause harm: Level (L) 1 "no potential harm", L2 "monitoring or intervention potentially required to preclude harm", and L3 "potential harm". This scale was also designed to take into account patient's clinical characteristics and high-risk drugs. RESULTS: 256 patients were included. Mean age was 82.2 ± 7.2 years old. 85 patients (33.2%) had ≥ 1 unintentional discrepancies. Overall, there were 173 unintentional discrepancies. The 3 most common drug classes involved in errors were nervous system (22.0%), gastrointestinal (20.0%) and cardiovascular (18.0%) medications. The most common types of errors were "omission" (87.9%) and "incorrect dose" (8.1%). Among the unintentional discrepancies, 20.8% had the potential to require increased monitoring or intervention to preclude harm (L2) and 6.4% had the potential to cause clinical deterioration (L3). CONCLUSION: More than 25% of the identified errors presented a potential clinical impact. These results show that a combined intervention of pharmacists and physicians in a collaborative medication reconciliation process has a high potential to reduce clinical relevant errors at hospital admission.

Pragmatic diabetes management in nursing homes: individual care plan.

Although the management of diabetes as a simple entity has been extensively developed, there is a dearth of evidence in elderly, frail patients with multiple comorbidities and polymedication. This population represents a large proportion of the residents of nursing homes (NHs). As a multidisciplinary group of French experts (geriatricians, endocrinologists, diabetologists, and general practitioners) with practical experience in this area, which is growing in magnitude throughout the world, we convened to compile pragmatic, simple advice on the management of elderly, frail diabetic patients. Given demands on NH personnel (manager, medical coordinator, nurses, and, at the front line of care provision, the undertrained and overworked carers), coupled with the quasiconstant of high staff turnover, the foundation stone of a patient's diabetes management is an Individual Care Plan (ICP) expressed in layman's language. This document that is opened on the patient's admission aims to make sure that the prescriptions established at admission are followed, notably to ensure correct treatment and adapted, regular monitoring with dates and times when examinations and tests are due. This includes monitoring of the diabetes control (HbA1c and, if necessary, blood and urine glucose) and its complications (cardiovascular disease, hypoglycemia, ocular problems, foot disorders, malnutrition, peripheral neuropathy, kidney failure). A necessary corollary is the training of staff to understand the specificities of caring for a frail patient with diabetes, on what to do in a potential emergency, and how to keep the ICP up to date for consultation by doctors and nurses.

[Dipeptidyl peptidase-4 inhibitors in type 2 diabetic elderly patient]. / Les inhibiteurs de la dipeptyl-peptidase-4 (DPP-4) chez le patient âgé diabétique de type 2.

The increase in prevalence and the particularities of care in old diabetic patients, which accumulate consequences of both, age and diabetes, the treatment must be well tolerated. The main adverse event is a hypoglycemia risk because of its major consequences for the elderly diabetic subjects. Since few years, three dipeptydil-peptidase-4 inhibitors (DPP-4), for which some studies have included type 2 diabetic old subjects are available in Europe. Their efficiency and their tolerance do not differ significantly from those noted at the younger diabetics. The reduced risk of hypoglycemia and the absence of influence on the weight are two interesting arguments to use them in the old diabetic patients. It remains however necessary to realize studies led specifically to old and even oldest subjects, corresponding to those in daily practice. If the data on their tolerance is confirmed, it could intend to revise therapeutic target for the old diabetic patients.

[Chronic fever revealing an urachal cyst]. / Fièvre au long cours révélant un kyste de l'ouraque.

In the adult, the urachus remains as a non-specific fibrous formation extended from the bladder dome to the Retzius space. This urachal remnant is commonly asymptomatic or may be revealed by a cyst. This later may also be asymptomatic or lead to local inflammation or inflammatory pseudo-tumor. We report an original observation of chronic fever revealing an urachal cyst in a 21-Year-old male.

The value of the Von Reyn and the Duke diagnostic criteria for infective endocarditis in internal medicine practice. A study of 38 cases.

BACKGROUND: The aim of our study was to compare the value of the Von Reyn and the Duke diagnostic criteria for infective endocarditis (IE) in internal medicine practice. METHODS: We determined the sensitivity and negative predictive value of these two sets of diagnostic criteria in 38 patients with established infective endocarditis who were followed in two departments of general internal medicine. The patients essentially had subacute endocarditis of the aortic valve (79%) with several systemic manifestations (100%). Microbial documentation included mainly gram-positive cocci (60%). RESULTS: With transthoracic echocardiography (TTE), the sensitivities of the Duke and the Von Reyn criteria were 65% and 35%, respectively, while with transesophageal echocardiography (TEE), these sensitivities were 75% and 35%, respectively. With TTE and TEE, the negative predictive values were 100% for the Duke diagnostic criteria versus only 71% for the Von Reyn criteria. CONCLUSIONS: This study confirms that the Duke diagnostic criteria are useful in practice for the management of patients with infective endocarditis followed in internal medicine.

Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature.

BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Bénichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05). CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality.

Vitamin B12 (cobalamin) deficiency in elderly patients.

Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.