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Intensive Treatment (intensive + treatment)
Selected AbstractsThe prevalence of diabetic retinopathy in patients with screen-detected type 2 diabetes in Denmark: the ADDITION studyACTA OPHTHALMOLOGICA, Issue 3 2009Toke Bek Abstract. Background:, The prevalence of type 2 diabetes is increasing, but the exact prevalence of the disease and its accompanying late complications are unknown. In the Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-detected Diabetes in Primary Care (ADDITION study), patients with hitherto undiagnosed type 2 diabetes are identified using a stepwise screening strategy in selected general practices. This article reports the occurrence of diabetic retinopathy in this population. Methods:, In Århus and Copenhagen counties, a total of 12 708 of the persons invited by mail were screened for diabetes mellitus. Consequently, 763 persons with type 2 diabetes were identified; 670 of these (335 from each of the two centres) underwent a general physical examination (including measurement of blood pressure and HbA1c) and an ophthalmological examination (including measurement of visual acuity and fundus photography). Retinopathy was graded from the photographs by counting all retinopathy lesions. Results:, Forty-five (6.8%) of the examined patients had any retinopathy, of which the majority was minimal. No patients had severe non-proliferative or proliferative diabetic retinopathy. There was no significant difference between age, sex and visual acuity among patients with and without retinopathy. However, the patients with retinopathy had significantly higher HbA1c and systolic and diastolic blood pressure than the patients without retinopathy. Conclusion:, Patients with screen-detected diabetes have a low prevalence of diabetic retinopathy and no vision-threatening lesions. Screening for diabetic retinopathy should be focused on those patients who have already been diagnosed with type 2 diabetes during routine clinical practice. [source] Insulin therapy and quality of life.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S1 2009A review Abstract Three central goals in the treatment of diabetes mellitus are (1) the avoidance of hyperglycaemia to prevent the development or progression of diabetes complications over time, (2) the avoidance of hypoglycaemia and (3) the maintenance or achievement of good quality of life. Insulin is the most powerful agent that can be used to control blood glucose levels. This article reviews the studies that have investigated the effects of different types of insulin and insulin delivery techniques on quality of life of patients with type 1 or type 2 diabetes. First, the concept of ,quality of life' (QoL) is defined and different ways of measuring QoL are explained. Secondly, the effects of different aspects of insulin therapy on QoL are reviewed: (1) the phenomenon of ,psychological insulin resistance'; (2) the effects of different types of insulin: regular insulin versus short-acting insulin analogues, long-acting insulin analogues or biphasic mixtures; (3) multiple daily injections versus pump therapy. Having multiple complications of diabetes is clearly associated with decreased QoL. Results from large studies such as the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) suggest that intensive treatment itself does not impair QoL. Recent findings further suggest that pump therapy, compared to multiple daily injections, has beneficial effects on QoL. The fact that multiple tools are used to assess QoL makes it difficult to draw conclusions regarding the effects of different types of insulin on QoL. More work on the standardization of the assessment of QoL in diabetes is urgently needed. Copyright © 2009 John Wiley & Sons, Ltd. [source] Peripheral arterial disease in diabetes,a reviewDIABETIC MEDICINE, Issue 1 2010E. B. Jude Diabet. Med. 27, 4,14 (2010) Abstract Diabetic patients are at high risk for peripheral arterial disease (PAD) characterized by symptoms of intermittent claudication or critical limb ischaemia. Given the inconsistencies of clinical findings in the diagnosis of PAD in the diabetic patient, measurement of ankle-brachial pressure index (ABI) has emerged as the relatively simple, non-invasive and inexpensive diagnostic tool of choice. An ABI < 0.9 is not only diagnostic of PAD even in the asymptomatic patient, but is also an independent marker of increased morbidity and mortality from cardiovascular diseases. With better understanding of the process of atherosclerosis, avenues for treatment have increased. Modification of lifestyle and effective management of the established risk factors such as smoking, dyslipidaemia, hyperglycaemia and hypertension retard the progression of the disease and reduce cardiovascular events in these patients. Newer risk factors such as insulin resistance, hyperfibrinogenaemia, hyperhomocysteinaemia and low-grade inflammation have been identified, but the advantages of modifying them in patients with PAD are yet to be proven. Therapeutic angiogenesis, on the other hand, represents a promising therapeutic adjunct in the management of PAD in these patients. Outcomes after revascularization procedures, such as percutaneous transluminal angioplasty and surgical bypasses in diabetic patients, are poorer, with increased perioperative morbidity and mortality compared with that in non-diabetic patients. Amputation rates are higher due to the distal nature of the disease. Efforts towards increasing awareness and intensive treatment of the risk factors will help to reduce morbidity and mortality in diabetic patients with PAD. [source] Motivational enhancement and coping skills training for cocaine abusers: effects on substance use outcomesADDICTION, Issue 7 2004Damaris J. Rohsenow Abstract Aims This clinical trial investigated effects of motivational enhancement treatment (MET) and group coping-skills training (CST) tailored for cocaine dependence. Effects of MET were hypothesized to be greater with CST and for less motivated patients. Design and interventions A 2 × 2 design investigated two individual sessions of MET compared to meditation,relaxation (MRT), followed by four group sessions of CST versus drug education (ED), as daily adjuncts to intensive treatment. Setting The substance abuse program provided full-day treatment with a learning-theory and 12-Step orientation. Participants Cocaine-dependent patients were recruited. Measurements Assessment included treatment retention; change in cocaine-related urge, self-efficacy, pros and cons, and motivation; substance use and problems during 12-month follow-up. Findings Of 165 patients, follow-up status is known for 90% (n = 149). Patients in MET with low initial motivation to change reported less cocaine and alcohol relapse and use days and fewer alcohol problems than MET patients with higher initial motivation. MET produced more employment improvement than MRT, with no other significant benefit for MET. Patients with higher motivation had more cocaine use and alcohol problems after MET than MRT. Group CST reduced cocaine and alcohol use during follow-up for women only and reduced alcohol relapse for men and women. Conclusions MET is more beneficial for patients with lower initial motivation than for patients with high initial motivation. CST reduced cocaine and alcohol use for women only and reduced alcohol relapses, in contrast to results with lengthier individual CST. [source] Educational needs, metabolic control and self-reported quality of lifeEUROPEAN DIABETES NURSING, Issue 1 2005A study among people with type 2 diabetes treated in primary health care Abstract The prevalence of type 2 diabetes is increasing. In order to reduce long-term complications and to promote a better life for these patients, health care professionals are important advocates in education and counselling. More knowledge is therefore needed to explore the association between educational needs and quality of life. In total, 211 people with type 2 diabetes (response rate 48%) were recruited from general practices in a geographically well-defined district in Bergen, Norway. All participants completed a questionnaire measuring demographical and clinical variables, quality of life (WHOQOL-Bref), satisfaction with education and counselling, and symptoms related to the disease. A blood sample was taken from each patient for determination of HbA1c. The participants reported receiving most information on diet, physical activity and treatment and less information on foot care and long-term complications. Satisfaction with education was significantly positively correlated with self-reported overall quality of life, and quality of life within domains for psychological health, social relationships and environment. More intensive treatment was significantly associated with lower quality of life within the physical health and social relationships domains. For 32% of the participants, HbA1c values did not satisfy the Norwegian guidelines (adjusted for age). The results from the present study emphasise a need for health education in diabetes primary health care especially in relation to foot care and long-term complications. The association between satisfaction with education and quality of life makes it important to develop educational and counselling methods for nurses in primary health care. Copyright © 2005 FEND. [source] Prophylactic therapy for haemophilia: early experienceHAEMOPHILIA, Issue 2003E. Berntorp Summary., During the 1960s, it was reported from Sweden that haemophiliacs with factor levels above 1% rarely develop arthropathy. This observation suggested that severe haemophilia could be converted to a milder form by regular infusions with factor concentrate. After several earlier publications, a report was published in 1992 that detailed 25 years' experience with prophylaxis in 60 patients from the Malmö centre. The results showed that starting prophylaxis early in life with a dose regimen that would prevent factor VIII or IX plasma levels from falling below 1% could prevent the development of haemophilic arthropathy. Also, older age groups who had received less intensive treatment, and who started prophylaxis later in life, were still in a much better condition than historic controls. In the 1970s several small but well-controlled studies from the USA, Germany and Italy clearly showed the benefit of prophylaxis in reducing bleeding frequency. Early experience from the Netherlands was published in 1971. Since these early studies, the results have been corroborated from many countries and in a large multinational study. Although the benefits of prophylaxis seem unquestionable, several research questions remain to be better elucidated, such as when to start and when to stop, dosing and dose interval, and how to assess the long-term treatment effects. These issues are of great economic importance, and the need for health economical studies is obvious. [source] Changes in treatment strategies for severe haemophilia over the last 3 decades: effects on clotting factor consumption and arthropathyHAEMOPHILIA, Issue 5 2001K. Fischer A cohort study was performed among 214 patients with severe haemophilia, born 1944,1994, to describe changes in treatment over the last 3 decades and its effects on clotting factor consumption and haemophilic arthropathy. Data on treatment strategy, clotting factor consumption, and outcome were collected for 3567 patient years (from 1972 to 1998), and 493 Pettersson scores were analysed. Median follow up was 17 years (range 6,27 years), and median age in 1998 was 27.6 years. Since 1965, replacement therapy, prophylaxis, and home treatment have been used and treatment intensified. Over the last 3 decades, annual clotting factor consumption increased by 260%, for both prophylactic and on-demand treatment. Annual clotting factor consumption kg,1 increased during childhood and appeared to stabilize in early adulthood for patients born 1965,79, who were treated with early replacement therapy or early prophylaxis. In contrast, clotting factor consumption increased continuously for patients born before 1965, who had had no access to replacement therapy during the early years of their life. The annual number of joint bleeds decreased over the years. Arthropathy as measured by the Pettersson score generally became apparent around the age of 15 years and was lowest in patients treated with primary prophylaxis. In conclusion, clotting factor consumption has increased and haemophilic arthropathy has decreased due to the intensification of treatment for severe haemophilia over the last 3 decades. Annual clotting factor consumption stabilizes in adulthood for patients who receive early intensive treatment. [source] Insulin intensification , the rationale and the targetINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2009A. Liebl Summary Aims:, To review the key evidence supporting targets for glycaemic control in people with type 2 diabetes and the implications for management in primary care. Method:, Literature review. Results:, Achieving early glycaemic control may reduce long-term risk by minimising the ,metabolic memory' effect of hyperglycaemia. Several large studies have failed to confirm expectations that intensive treatment would offer greater reductions in risk. This may reflect the failure to achieve control blood glucose early in the course of diabetes. Management guidelines emphasise the importance of targets for glycaemic control, but differ in the strategies they recommend for dose intensification. All, however, acknowledge the importance of individualising treatment. Conclusion:, Early achievement of targets for glycaemic control may be important to reduce long-term risk in people with diabetes, but treatment should be tailored to individual need. [source] Biochemical markers of bone turnover and bone mineral density in patients with ,-thalassaemia majorINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2005E. Eren Summary In this study, bone formation markers (bone-specific alkaline phosphatase and osteocalcin) and bone resorption markers (pyridinoline and deoxypyridinoline) were analysed. Bone formation, as evidenced by the levels of serum alkaline phosphatase and osteocalcin, did not appear to be impaired, while bone resorption was grossly increased in all patient groups. The decrease of bone mineral density values was more prominent in the lumbar spine, thus making this site particularly interesting for such studies. The patients had significantly lower femoral neck and lumbar spine bone mineral density when compared with control (all p < 0.001). Our conclusion is that, in spite of the severe bone destruction that occurs in thalassaemia major, the fact that bone formation remains intact calls for a more intensive treatment. [source] Timing and prediction of relapse in a transdiagnostic eating disorder sampleINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 7 2008Traci McFarlane PhD Abstract Objective: To identify factors that predict relapse in eating disorders to direct the development of effective relapse prevention interventions. Method: Fifty-eight participants who had partially remitted from their eating disorder after intensive treatment were prospectively followed for up to 24 months. A transdiagnostic sample was included based on current recommendations. Results: The 12-month survival rate was 0.59, indicating that 41% of the sample had relapsed at this time, and four factors emerged as significant predictors of relapse. These factors included more severe pretreatment caloric restriction, higher residual symptoms at discharge, slower response to treatment, and higher weight-related self-evaluation. Conclusion: Clinical recommendations based on these data include encouraging clients to adopt the recommended behavioral changes immediately at the beginning of treatment, and to make complete symptom control a priority. In addition, addressing weight-related self-evaluation and teaching clients to detach from this schema that connects weight/shape with self-esteem may be an effective and feasible step toward relapse prevention. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [source] Estimating readiness for change in anorexia nervosa: Comparing clients, clinicians, and research assessorsINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2002Josie Geller Abstract Objective This research compared the relative ability of clients, clinicians, and research assessors in estimating readiness for change in individuals with anorexia nervosa. Method Fifty-six individuals with a current or past diagnosis of anorexia nervosa made ratings of the extent to which they perceived themselves to be ready for treatment and recovery. Clinicians and research assessors made the same ratings based on their impressions following clinical and research assessments, respectively. The outcome variables included questionnaire measures of change activities, assigned behavioral tasks, and clients' decision to accept intensive treatment. Results While research assessor and client ratings predicted questionnaire recovery activities, only research assessor ratings predicted completion of behavioral tasks and clients' decision to accept intensive treatment. Clinician ratings were not related to any of the questionnaire or behavioral recovery activity measures. Discussion Conditions favoring the accurate prediction of readiness for treatment and recovery are discussed, and implications for clinical practice are addressed. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 251,260, 2002; DOI 10.1002/eat.10045 [source] Role of the MRP1/ABCC1 Multidrug Transporter Protein in CancerIUBMB LIFE, Issue 12 2007Marcia Munoz Abstract Multidrug resistance is a major obstacle to cancer treatment and leads to poor prognosis for the patient. Multidrug resistance-associated protein 1 (MRP1) transports a wide range of therapeutic agents as well as diverse physiological substrates and may play a role in the development of drug resistance in several cancers including those of the lung, breast and prostate, as well as childhood neuroblastoma. The majority of patients with neuroblastoma present with widely disseminated disease at diagnosis and despite intensive treatment, the prognosis for such patients is dismal. There is increasing evidence that MRP1 is a MYCN target gene involved in the development of multidrug resistance in neuroblastoma. Given the importance of MRP1 overexpression in neuroblastoma, MRP1 inhibition may be a clinically relevant approach to improving patient outcome in this disease. [source] Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Tim Cundy MD Abstract In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability. Introduction: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy. Materials and Methods: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored. Results: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1,3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p < 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from ,2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis. Conclusions: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization. [source] The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic reviewJOURNAL OF INTERNAL MEDICINE, Issue 1 2004M. G. Wulffelé Abstract. Background., The UKPDS 34 showed that intensive treatment with metformin significantly reduces macrovascular end-points and mortality in individuals with newly diagnosed type 2 diabetes compared with intensive treatment with insulin or sulphonylurea derivatives, despite similar glycaemic control. How this should be explained is as yet unclear. We hypothesized that metformin may have a glucose-lowering independent effect on blood pressure and lipid profile. In order to test this hypothesis we systematically reviewed the literature and pooled the data obtained in a meta-analysis. Methods., Included were randomized-controlled trials in patients with type 2 diabetes mellitus and metformin treatment lasting at least 6 weeks. To identify all eligible trials we conducted electronic searches using the bibliographic databases Medline and Embase, contacted the manufacturer and checked obtained publications for cross-references. Results., Forty-one studies (3074 patients) provided data on blood pressure and/or lipid profile. When compared with control treatment, metformin associated effects on systolic and diastolic blood pressure and HDL cholesterol were small and statistically not significant [,1.09 mmHg 95% confidence interval (,3.01,0.82), P = 0.30; ,0.97 (,2.15,0.21) mmHg, P = 0.11 and +0.01 (,0.02,0.03) mmol L,1, P = 0.50, respectively]. Compared with control treatment, however, metformin decreased plasma triglycerides, total cholesterol and LDL cholesterol significantly [,0.13 (,0.21,,0.04) mmol L,1, P = 0.003; ,0.26 (,0.34,,0.18) mmol L,1, P < 0.0001 and ,0.22 (,0.31,,0.13) mmol L,1, P < 0.00001, respectively]. We found no indications for publication bias. Of note, glycaemic control as assessed by HbA1c was better with metformin than with control treatment [,0.74 (,0.84,,0.65) percentage point; P < 0.00001]. When studies were subdivided into tertiles according to increasing difference in glycaemic control between metformin and control treatment, it appeared that in case of near similar glycaemic control metformin had no effect versus control treatment on triglycerides, whereas still there was a significant effect on total and LDL cholesterol. Conclusions., This meta-analysis of randomized-controlled clinical trials suggests that metformin has no intrinsic effect on blood pressure, HDL cholesterol and triglycerides in patients with type 2 diabetes. This drug, however, independent of its effect on glycaemia, reduces total and LDL cholesterol significantly, but the reductions in these variables are relatively small. [source] Group A streptococcal toxic shock syndrome with extremely aggressive course in the third trimesterJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2010Takashi Sugiyama Abstract Group-A-streptococcus-(GAS)-induced toxic shock syndrome (TSS) is uncommon, but carries a high risk of maternal mortality during pregnancy. The onset of gravidic GAS-TSS has been reported mostly during the puerperium. A 16-year-old woman, who was at 37 weeks of gestation, and without obstetrical care during the last 30 weeks, was referred to our hospital. She complained of fever for one day with headache and abdominal pain after the fever developed. On admission, her consciousness was drowsy, intrauterine fetal death was recognized, and she rapidly developed shock status with coma and hypotension, hemolysis, disseminated intravascular coagulation (DIC), and multi-organ failure. Although we had not obtained the results of a bacterial culture, we suspected sepsis with DIC with homolysis and multi-organ failure resulting from an infection. The patient was treated with antibiotics and intubation because of respiratory insufficiency. Twelve hours after admission to the intensive care unit in our hospital, she died. Cultures from blood, subcutaneous tissue, vaginal discharge, and pharynx all revealed GAS bacteria, and therefore she was diagnosed as having GAS-TSS. GAS-TSS in pregnancy is rare. However, once the infection occurs in a pregnant woman, it rapidly develops into sepsis with multi-organ failure. Therefore, early recognition and intensive treatment for GAS during pregnancy is recommended in women with high fever, muscular pain, hemolysis and DIC during pregnancy. [source] Withdrawal of neonatal mechanical ventilation against the parents' wishesJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2006David Isaacs Abstract: Neonatologists and parents usually agree when intensive treatment should be stopped. We describe the management of two babies where there was disagreement between the parents and hospital staff, and discuss the medical, legal and ethical implications of the two cases. [source] REVIEW ARTICLE: Hyperglycemia: a prothrombotic factor?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2010B. A. LEMKES Summary., Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaired fibrinolysis. Hyperglycemia plays an important role in the development of these hemostatic abnormalities, as is illustrated by the association with glycemic control and the improvement upon treatment of hyperglycemia. Interestingly, stress induced hyperglycemia, which is often transient, has also been associated with poor outcome in thrombotic disease. Similar laboratory findings suggest a common effect of acute vs. chronic hyperglycemia on the coagulation system. Many mechanisms have been proposed to explain this prothrombotic shift in hyperglycemia, such as a direct effect on gene transcription of coagulation factors caused by hyperglycemia-induced oxidative stress, loss of the endothelial glycocalyx layer, which harbours coagulation factors, and direct glycation of coagulation factors, altering their activity. In addition, both chronic and acute hyperglycemia are often accompanied by hyperinsulinemia, which has been shown to have prothrombotic effects as well. In conclusion, the laboratory evidence of the effects of both chronic and acute hyperglycemia suggests a prothrombotic shift. Additionally, hyperglycemia is associated with poor clinical outcome of thrombotic events. Whether intensive treatment of hyperglycemia can prevent hypercoagulability and improve clinical outcome remains to be investigated. [source] Glycemic Targets for Patients with Type 2 Diabetes MellitusMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2009Ole-Petter R. Hamnvik MB Abstract Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins. Mt Sinai J Med 76:227,233, 2009. © 2009 Mount Sinai School of Medicine [source] Past, present, and future of insulin pump therapy: better shot at diabetes controlMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2008Jennifer Sherr MD Abstract With the advent of continuous subcutaneous insulin infusion therapy and the findings of the Diabetes Control and Complications Trial, the management of type 1 diabetes has changed drastically. Over the past 30 years since its development, the effectiveness of continuous subcutaneous insulin infusion has been assessed in comparison with other modes of intensive treatment. Additionally, improvements in pump delivery systems have been made. Here, the findings of the studies on pump therapy are reviewed. Selection criteria of patients for pump use and how to initiate pump therapy are presented. Finally, newer findings on continuous glucose sensors are discussed as the next era of pump therapy continues to focus on the goal of developing an artificial pancreas. Mt Sinai J Med 75:352,361, 2008. © 2008 Mount Sinai School of Medicine [source] Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian originPEDIATRIC BLOOD & CANCER, Issue 2 2009Karin Beutel MD Abstract Background Epstein-Barr virus (EBV) is one of the most frequent triggers of hemophagocytic lymphohistiocytosis (HLH). EBV-associated HLH (EBV-HLH) and ectopic infection of T cells has been particularly described in patients from Far East Asia. Procedure In a cohort of 12 children with EBV-HLH treated in Germany, the EB viral load was detected by real-time polymerase chain reaction in plasma and peripheral blood mononuclear cells (PBMC). Virological and clinical data were analyzed retrospectively. Results Among the 12 mainly German patients, children with underlying immunodeficiencies as well as otherwise healthy individuals were affected. The clinical course ranged from a steroid-responding to a fatal disease despite intensive treatment. Increased EBV copy numbers in plasma and/or PBMC were found in all patients. Serial measurements reflected the course of the disease. Cell-type specific viral load was determined in seven patients and revealed EBV-infection of T cells in all of them. In contrast to the reported Asian patients a significant viral load was also found in B cells. Conclusions T cell infection appears to be a typical feature of EBV-associated HLH irrespective of patients ethnic background and the clinical course. Evaluation of cell-type specific infection should be considered when targeted therapy is applied. Pediatr Blood Cancer 2009;53:184,190. © 2009 Wiley-Liss, Inc. [source] Familial Currarino syndrome presenting with peripheral primitive neuroectodermal tumour arising with a sacral teratomaPEDIATRIC BLOOD & CANCER, Issue 1 2008G. Sen MD Abstract This report illustrates a rare genetic disorder, Currarino syndrome, in association with an unusual malignant transformation to a peripheral primitive neuroectodermal tumour within a sacral teratoma. The triad of features consists of a presacral mass, partial sacral agenesis and anorectal anomalies. The most common presentation is constipation. In this case there was a history of constipation, teratomas and spinal abnormalities in many of the family members over three generations. Detailed family history taken at time of initial presentation may have prevented delay in diagnosis and averted the need for intensive treatment, which may well cause late sequelae. Pediatr Blood Cancer 2008;50:172,175. © 2006 Wiley-Liss, Inc. [source] Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008Donatella Baronciani In recent years, new conditioning regimens have been explored in patients not eligible for conventional transplant with the aim to reduce transplant-related mortality. In a phase II multicentric prospective trial, we investigated the safety and feasibility of the treosulfan,fludarabine combination prior to allogeneic hematopoietic stem cell transplant in patients with various hematological malignancies not eligible for conventional regimens because of previous intensive treatment, older age, and comorbidities. Forty-six consecutive patients, median age 48 years (range 17,69), were enrolled. Sixteen of them were in complete remission, and 20 had a HSCT comorbidity index , 1. Forty-four patients had regular and sustained engraftment, and 39 out of 40 evaluable patients developed complete chimerism. Nonhematological toxicity was limited. Risk of transplant-related mortality was 9% (95% CI, 2,17%) at day +100 and plotted at 15% (95% CI, 7,22%) after 7 months. The estimated overall survival and progression-free survival with a median follow-up of 20 months were 51% and 38%, respectively. The estimated 30 months progression-free survival for patients transplanted in remission was 56%. The treosulfan,fludarabine combination is a reduced-toxicity but myeloablative regimen that can be proposed to patients not fitting criteria for conventional transplant regimens. Longer follow-up and further prospective studies are necessary to evaluate this regimen. © 2008 Wiley-Liss, Inc. Am. J. Hematol., 2008. [source] Latest news and product developmentsPRESCRIBER, Issue 4 2008Article first published online: 20 MAR 200 Suicide warning for all antidepressants All antidepressants are to include a warning of the risk of suicide in their product information, the MHRA says. The requirement formerly applied only to SSRIs but, following a US review of safety data, the Agency says the risk is similar for all classes of antidepressants. Patients at increased risk include young people with psychiatric morbidity and those with a history of suicidal ideation. Patients are at increased risk of suicide until remission occurs, and clinical experience shows that the risk is increased during the early stages of recovery. Confusion over type 2 diabetes management Contradictory findings have been reported from two studies of intensive management of type 2 diabetes. The STENO-2 study (N Engl J Med 2008;358:580-91) found that tight control of blood glucose, blood pressure and lipids plus low-dose aspirin in 160 patients with type 2 diabetes and microalbuminuria significantly reduced all-cause mortality, cardiovascular events, cardiovascular death and microvascular complications by 40-60 per cent. The US National Heart, Blood and Lung Institute has announced the end of the intensive treatment arm of the ACCORD study (unpublished). This study was comparing intensive lowering of blood glucose below currently recommended levels (target HbA1C <6 per cent) with conventional management in adults with type 2 diabetes at especially high risk for heart attack and stroke. Although mortality was reduced in both arms compared with other populations, intensive treatment was associated with increased mortality equivalent to three deaths per 1000 patients per year over four years. Another antibiotics campaign The Government has launched another campaign to promote public awareness that antibiotics are not appropriate for viral infections causing coughs, colds and sore throats. Get Well Soon , Without Antibiotics is supported by a national advertising campaign and leaflets and posters encouraging the public to ask advice rather than demand a prescription. Details are available at www.dh.gov.uk. Episenta: once-daily sodium valproate Following a launch to specialists last year, a new once-daily modified-release formulation of sodium valproate is being promoted more widely to GPs. Episenta is licensed for the treatment of all forms of epilepsy and is formulated as modified-release capsules of 150mg and 300mg and sachets of modified-release granules of 500mg and 1000mg. The dose may be administered once or twice daily. Patients may be switched from enteric-coated tablets of valproate to the same dose given as Episenta. Episenta costs £5.70 or £10.90 for 100 × 150mg or 300mg capsules, and £18 or £35.50 for 100 × 500mg or 1000mg sachets. Latest NICE agenda The Department of Health has referred a new batch of topics for appraisal by NICE. Six of seven technology appraisals are for cancer drugs; the last is for dabigatran etexilate for venous thromboembolism. There will be four new clinical guidelines: autism spectrum disorders, hypertension in pregnancy, bed-wetting in children and severe mental illness with substance abuse. Two combined public health and clinical guidelines will address alcohol misuse. Varenicline vs NRT Varenicline (Champix) offers slightly greater smoking cessation rates than nicotine replacement therapy (NRT) in the long term and better symptom improvement, an international study has shown (Thorax 2008; published online:10.1136/ thx.2007.090647). A total of 746 smokers were randomised to treatment with varenicline 1mg twice daily for 12 weeks or transdermal NRT (21mg reducing to 7mg per day) for 10 weeks. Continuous abstinence rates for the last four weeks of treatment were 56 vs 43 per cent. The corresponding rates for one year were 26 and 20 per cent. Varenicline was associated with greater reductions in cravings, withdrawal symptoms and smoking satisfaction, but more nausea (37 vs 10 per cent). Adverse reactions class effect of statins The MHRA has identified several adverse effects that it says are class effects of the statins (Drug Safety Update 2008;1:Issue 7). Following a review of clinical trials and spontaneous reports, it is now apparent that any statin may be associated with sleep disturbance, depression, memory loss and sexual dysfunction; interstitial lung disease has been reported rarely. Product information is being updated to include the new information. Depression, including suicidal ideation, has also been associated with varenicline (Champix), the MHRA says; affected patients should stop treatment immediately. The combination of transdermal nicotine replacement therapy (NRT) and varenicline appears to be associated with a higher incidence of nausea, headache, vomiting, dizziness, dyspepsia and fatigue than NRT alone. The MHRA has also announced that, following the suspension of marketing authorisation for carisoprodol (Carisoma), it is considering a phased withdrawal of the closely-related meprobamate , the main active metabolite of carisoprodol. Following a successful pilot study, the public are being encouraged to report adverse reactions on yellow cards; the MHRA notes that health professionals provide more complete reports but patients include more information about quality of life. The scheme will be promoted via community pharmacies throughout the UK from February 2008. Cochrane: evidence on back pain interventions The latest release of Cochrane reviews includes three meta-analyses assessing interventions for back pain. Overall, NSAIDs were found to be effective as short-term treatment for acute or chronic back pain but the effect size was small. They were comparable with paracetamol but associated with more adverse effects; COX-2 selective NSAIDs were similarly effective, with slightly fewer adverse effects. There was no evidence that antidepressants reduced back pain but intensive individual patient education (lasting 2.5 hours) was effective for acute and subacute back pain and comparable with manipulation and physiotherapy; its effects on chronic pain were unclear. Copyright © 2008 Wiley Interface Ltd [source] Behavioural functioning of retinoblastoma survivorsPSYCHO-ONCOLOGY, Issue 1 2009J. van Dijk Abstract Objective: To assess behavioural problems in retinoblastoma (RB) survivors. Methods: This population-based cross-sectional study included 148 RB survivors (8,35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self-reports and proxy reports. One-sample T -tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample. Results: Between-group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8,17 years); this against 9% in adolescents (12,17 years) and 12% in adults (18,35 years) based on self-report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self-reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single-parent family were identified to be at most behavioural risk. Conclusion: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties. Copyright © 2008 John Wiley & Sons, Ltd. [source] Evolution of pancreas transplant surgeryANZ JOURNAL OF SURGERY, Issue 6 2010Vincent W. T. Lam Abstract Background:, Type 1 diabetes mellitus is a chronic condition often leading to disabling complications including retinopathy, neuropathy and cardiovascular disease which can be modified by intensive treatment with insulin. Such treatment, however, is associated with a restrictive lifestyle and risk of hypoglycaemic morbidity and mortality. Methods:, This review examines the role of pancreas transplantation in patients with Type 1 diabetes mellitus. Results:, Pancreas transplantation is currently the only proven option to achieve long-term insulin independence, resulting in an improvement or stabilization of those diabetic related complications. The hazards of pancreas transplantation as a major operation are well known. Balancing the risks of a surgical procedure, with the benefits of restoring normoglycaemia remains an important task for the pancreas transplant surgeon. Pancreas transplantation is not an emergency operation to treat poorly managed and non-compliant patients with debilitating complications. It is a highly specialized procedure which has evolved both in terms of the surgical technique, patient selection and assessment. Conclusion:, Pancreas transplantation has emerged as the single most effective way to achieve normal glucose homeostasis in patients with Type 1 diabetes mellitus. [source] Permanent sacral nerve stimulation for treatment of idiopathic constipationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2002N. J. Kenefick Background: Constipation can usually be managed using conservative therapies. A proportion of patients require more intensive treatment. Surgery provides variable results. This paper describes an alternative approach, in which the neural control of the bowel and pelvic floor is modified, using permanent sacral nerve stimulation. Methods: Four women (aged 27,36 years), underwent temporary and then permanent stimulation. All had idiopathic constipation, resistant to maximal therapy, with symptoms for 8,32 years. Clinical evaluation, bowel diary, Wexner constipation score, symptom analogue score, quality of life questionnaire and anorectal physiology were completed. Results: There was a marked improvement in all patients with temporary, and in three with permanent, stimulation. Median follow-up was 8 (range 1,11) months. Bowel frequency increased from 1,6 to 6,28 evacuations per 3 weeks. Improvement occurred, at longest,follow,up, in median (range) evacuation score (4 (0,4) versus 1 (0,4)), time with abdominal pain (98 (95,100) versus 12 (0,100) per cent), time with bloating (100 (95,100) versus 12 (5,100) per cent), Wexner score (21 (20,22) versus 9 (1,20)), analogue score (22 (16,32) versus 80 (20,98)) and quality of life. Maximum anal resting and squeeze pressures increased. Rectal sensation was altered. Transit time normalized in one patient. Conclusion: Permanent sacral nerve stimulation can be used to treat patients with resistant idiopathic constipation. © 2002 British Journal of Surgery Society Ltd [source] Forum on: the role of recombinant factor VIII in children with severe haemophilia AHAEMOPHILIA, Issue 2 2009M. FRANCHINI Summary., The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970,1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first-choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on-demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti-FVIII alloantibodies, whereas other treatment-related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti-FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first-choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long-lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report. [source] Barriers to Treatment of Hepatitis C in HIV/HCV-Coinfected Adults with Alcohol ProblemsALCOHOLISM, Issue 9 2006David Nunes Background: Alcohol use and human immune deficiency virus (HIV) infection are both associated with accelerated progression of hepatitis C virus (HCV) disease and reduced response rates to interferon therapy. In this study, we assessed the prevalence of barriers to interferon treatment in a population of HIV/HCV-coinfected patients with current or past alcohol problems and the extent to which they received treatment to address the barriers. Methods: This is a cross-sectional, descriptive analysis of baseline data from a prospective study assessing the impact of HCV and alcohol use on HIV disease progression. Using consensus guidelines, subjects were categorized as having absolute, relative, or no contraindications to interferon therapy for HCV. Absolute contraindications to treatment included heavy alcohol use, decompensated liver disease, CD4 cell count <100 cells/,L, recent needle sharing, and suicidal ideation. Relative contraindications included moderate alcohol use, recent injection drug use, depressive symptoms, and CD4 cell count from 100 to 199 cells/,L. Results: Of 401 HIV-infected subjects, 200 were HCV RNA-positive. Fifty-three percent had an absolute contraindication to interferon therapy, 35% a relative but no absolute contraindication, and only 12% had no contraindication. Of those with an absolute contraindication, 61% reported heavy drinking and the majority (88%) had multiple contraindications. These contraindications were present despite the fact that over 50% were in receipt of substance abuse and mental health treatment. Conclusions: Continued alcohol and drug use as well as depressive symptoms are the major barriers to interferon therapy in HCV/HIV-coinfected subjects and these barriers persist despite high treatment rates for these problems. Therefore, more intensive treatments of alcohol, drug, and mental health issues are needed to improve HCV treatment eligibility in HCV/HIV-coinfected persons. [source] |