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Frequent Monitoring (frequent + monitoring)
Selected AbstractsToxicity in Doberman Pinchers with Ventricular Arrhythmias Treated with Amiodarone (1996,2005)JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009M.S. Kraus Background: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study. Hypothesis: Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn. Methods: Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs. Results: Reversible toxicity was identified in 10 of 22 (45%) dogs. Conclusion and Clinical Importance: Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly. [source] Peginterferon alpha-2b plus ribavirin vs interferon alpha-2b plus ribavirin for chronic hepatitis C in HIV-coinfected patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2007M. Crespo Summary., Treatment of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients is associated with low response rates and high incidence of side effects. One hundred twenty-one hepatitis C virus (HCV),HIV-coinfected patients were randomized to receive interferon alpha-2b (3 MU thrice weekly; n = 61) or peginterferon alpha-2b (1.5 ,g/kg/week; n = 60), plus ribavirin (800 mg daily), for 24 (genotype 2 or 3) or 48 weeks (genotype 1 or 4). We assessed early virological response at 4, 8 and 12 weeks to predict sustained virological response (SVR). Safety assessment included frequent blood lactate measurement and relative quantitation of mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells. In intention-to-treat analysis, the SVR rate was higher in the peginterferon group (55%vs 26%; P = 0.002). The difference for HCV genotypes 1 and 4 was 45%vs 14% (P = 0.009) and 50%vs 27% (P = 0.387), respectively, and for genotype 2 or 3, 71%vs 43% (P = 0.12) Viral response at 4, 8 and 12 weeks of treatment was highly predictive of SVR. Among genotype 3 patients, 17 of 20 (85%) whose HCV RNA was already undetectable at 4 weeks had an SVR after 24 weeks of treatment. Hyperlactataemia occurred in 22 patients and was clinically significant in six, two of whom died. mtDNA decreased significantly 4,12 weeks after the start of treatment in patients developing clinically significant hyperlactataemia. Peginterferon alpha-2b plus ribavirin was more effective than interferon alpha-2b plus ribavirin in HIV-coinfected patients. Frequent monitoring of virological response may be very helpful to optimize treatment compliance, to tailor treatment duration and to minimize side effects. [source] Frequent monitoring of temperature: an essential requirement for site selection in bivalve aquaculture in tropical,temperate transition zonesAQUACULTURE RESEARCH, Issue 10 2006Marķa Teresa Sicard Abstract Frequent monitoring of temperature (FMT) for over 1 year at two aquaculture sites in the western Baja California peninsula was analysed in terms of hourly, daily and monthly variability, and with this information, temperature-change indices were calculated. These data were contrasted against a long-term series from a global database (Extended Reconstruction of Sea Surface Temperature (ERSST)) to evaluate whether these could substitute for FMT. The compatibility of species requirements with the thermal conditions was evaluated by comparing the temperature frequency distributions from the two FMTs, with the optimum and lethal temperature information available on five bivalve species of aquacultural interest. We concluded that there was no correlation between ERSST and FMT because the former underestimates the amplitude of real temperature fluctuations and exhibits a different pattern of variation during the year. Therefore, FMT was needed for a correct selection of an aquaculture site for bivalves. The FMT indicated high temperature variability at both sites studied on different time scales, with the site located at lower latitude (Rancho Bueno) warmer and with a higher variability than Laguna Manuela. Contrasting these results with optimum and lethal temperature values of bivalve species, it was possible to find the ideal site, for temperature, for culturing the species, taking into account the variability associated with large-scale phenomena. [source] Autocatalytic Enantiomerisation at the Crystal Surface in Deracemisation of Scalemic ConglomeratesCHEMISTRY - A EUROPEAN JOURNAL, Issue 39 2009Shengwei Wei Dr. Abstract Deracemisation of racemic or scalemic conglomerates of intrinsically chiral compounds appears to be a promising method of chiral resolution. By combining the established methods of asymmetric synthesis and the physical process of crystal growth, we were able to achieve a complete deracemisation (with 100,%,ee) of an asymmetric Mannich product conglomerate,vigorously stirred in its saturated solution,from a starting enantiomeric excess value of 15.8,% in the presence of pyrrolidine (8,mol,%) as an achiral catalyst for the CC bond-forming reaction. Strong activation of this deracemisation process was observed on mild isothermal heating to only 40,°C, resulting in dramatic acceleration by a factor of about 20 with respect to the results obtained at room temperature. Despite the fact that the racemisation half-life time of the nearly enantiopure Mannich product (with 99,%,ee) in the homogenous solution at the reaction temperature is eight days, the deracemisation process took only hours in a small-scale experiment. This apparent paradox is explained by a proposed rapid enantiomerisation at the crystal/solution interface, which was corroborated by a 13C labelling experiment that confirmed the involvement of rapid enantiomerisation. Frequent monitoring of the solution-phase ee of the slowly racemising compound further revealed that the minor enantiomer dominated in solution, supporting an explanation based on a kinetic model. A generalisation of the process of "aymmetric autocatalysis" (resulting in automultiplication of chiral products in homogenous media) to encompass heterogeneous systems is also suggested. [source] Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trialDIABETIC MEDICINE, Issue 3 2006L. M. B. Laffel Abstract Aims Diabetic ketoacidosis (DKA), a life-threatening acute complication of Type 1 diabetes, may be preventable with frequent monitoring of glycaemia and ketosis along with timely supplemental insulin. This prospective, two-centre study assessed sick day management using blood 3-hydroxybutyrate (3-OHB) monitoring compared with traditional urine ketone testing, aimed at averting emergency assessment and hospitalization. Methods One hundred and twenty-three children, adolescents and young adults, aged 3,22 years, and their families received sick day education. Participants were randomized to receive either a blood glucose monitor that also measures blood 3-OHB (blood ketone group, n = 62) or a monitor plus urine ketone strips (urine ketone group, n = 61). All were encouraged to check glucose levels , 3 times daily and to check ketones during acute illness or stress, when glucose levels were consistently elevated (, 13.9 mmol/l on two consecutive readings), or when symptoms of DKA were present. Frequency of sick days, hyperglycaemia, ketosis, and hospitalization/emergency assessment were ascertained prospectively for 6 months. Results There were 578 sick days during 21 548 days of follow-up. Participants in the blood ketone group checked ketones significantly more during sick days (276 of 304 episodes, 90.8%) than participants in the urine ketone group (168 of 274 episodes, 61.3%) (P < 0.001). The incidence of hospitalization/emergency assessment was significantly lower in the blood ketone group (38/100 patient-years) compared with the urine ketone group (75/100 patient-years) (P = 0.05). Conclusions Blood ketone monitoring during sick days appears acceptable to and preferred by young people with Type 1 diabetes. Routine implementation of blood 3-OHB monitoring for the management of sick days and impending DKA can potentially reduce hospitalization/emergency assessment compared with urine ketone testing and offers potential cost savings. [source] Liver function test abnormalities in anorexia nervosa,Cause or effectINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 4 2010Vignesh Narayanan MD Abstract Objective: Two females with severe anorexia nervosa (BMI of 10) were seen with marked abnormalities in their liver function tests before the initiation of refeeding. These paradoxically resolved with progressive refeeding and weight restoration. Method: Clinical observation during regimented medical stabilization and refeeding of two patients with severe anorexia nervosa with frequent monitoring of liver function tests. Results: Normalization of liver function tests ensued as caloric intake increased and weight gain progressed. Discussion: Although classically liver function test elevations occur during refeeding, as a manifestation of excessive calories and fat deposition in the liver, they may also be elevated due to severe malnutrition before refeeding has commenced and improved as refeeding occurs. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010 [source] Hospitalized patients with acute decompensated heart failure: Recognition, risk stratification, and treatment reviewJOURNAL OF HOSPITAL MEDICINE, Issue S6 2008Alpesh Amin MD Abstract Acute decompensated heart failure (ADHF) has emerged as a major healthcare problem. It causes approximately 3% of all hospitalizations in the United States, with the direct medical cost of these hospitalizations estimated at $18.8 billion per year. Early recognition, risk stratification, and evidence-based treatment are crucial in reducing the morbidity, mortality, and costs associated with this disorder. Classic signs and symptoms of ADHF, such as rales, dyspnea, and peripheral edema, may be absent at hospital presentation and, even when present, are not specific to this disorder. As a result, serum B,type natriuretic peptide level is now used to rapidly and accurately detect ADHF. Multivariate analyses have identified renal dysfunction, hypotension, advanced age, hyponatremia, and comorbidities as significant and independent mortality risk factors. Based on these factors, mortality risk can be stratified from very low to very high using published algorithms that have been validated in independent populations. Evidence-based guidelines for the treatment of ADHF are available from both the European Society of Cardiology and the Heart Failure Society of America. In general, an intravenous loop diuretic, either alone or in combination with a vasodilator, is recommended as initial therapy in patients with volume overload, depending on the patient's clinical status. Use of inotropic agents should be limited to the small subset of patients with low-output syndrome and significant hypotension. In any event, frequent monitoring of clinical response is essential, with subsequent therapy determined by this response. Finally, focused patient education during hospitalization may help reduce readmissions for ADHF. Journal of Hospital Medicine 2008;3(Suppl 6):S16,S24. © 2008 Society of Hospital Medicine. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Endocrine Aspects of Sexual Dysfunction in MenTHE JOURNAL OF SEXUAL MEDICINE, Issue 1 2004Alvaro Morales MD ABSTRACT Introduction., Endocrine disorders of sex steroid hormones may adversely affect men's sexual function. Aim., To provide expert opinions/recommendations concerning state-of-the-art knowledge for the pathophysiology, diagnosis and treatment of endocrinologic sexual medicine disorders. Methods., An International Consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a scientific and debate process. Concerning the Endocrine committee, there were eight experts from seven countries. Main Outcome Measure., Expert opinions/recommendations are based on grading of evidence-based medical literature, extensive internal committee discussion over 2 years, public presentation and deliberation. Results., Hypogonadism is a clinical and biochemical syndrome characterized by a deficiency in serum androgen levels which may decrease sexual interest, quality of erections and quality of life. Biochemical investigations include testosterone and either bioavailable or calculated free testosterone; prolactin should be considered when hypogonadism has been documented. If clinically indicated, androgen therapy should maintain testosterone within the physiological range avoiding supraphysiologic values. Digital rectal examination and determination of serum prostate specific antigen values are mandatory prior to therapy and regularly thereafter. Androgen therapy is usually long-term requiring regular follow-up, frequent monitoring of blood levels and beneficial and adverse therapeutic responses. Conclusions., Safe and effective treatments for endocrinologic sexual medicine disorders examined by prospective, placebo-controlled, multi-institutional clinical trials are needed. [source] Systemic immunosuppressant therapy in childhoodCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2002David Atherton The indications for systemic immunosuppressant therapy are much the same in children as in adults. Perhaps the most important difference is the need in a child to consider more carefully the patient's likely future therapy requirements. This need reflects a justifiable anxiety concerning the longer-term toxicity associated with some of these drugs. It is obvious that special attention should be paid to the dosage regimens that are appropriate in children. However, otherwise the principles of treatment are essentially the same as in adults. This talk will focus on the use of azathioprine in atopic eczema, methotrexate in psoriasis and linear morphoea, and intravenous methylprednisolone in severe muco-cutancous erythema multiforme and toxic epidermal necrolysis. The value of azathioprine as a treatment for severe childhood eczema was greatly increased by the elucidation of the metabolic pathways for this drug, and by the development of an assay for thiopurine methyl transferase to allow detection of those at greatest risk of myelosuppression. We now treat children with normal TPMT levels with 3 mg/kg per day with gratifying therapeutic response and limited requirement for monitoring of blood counts and liver function. More recently we have successfully treated TPMTHL heterozygotes with doses of around 1.5 mg/kg per day. We now consider azathioprine as superior to cyclosporin as a systemic therapy for atopic eczema. The value of methotrexate in adults with plaque psoriasis and generalized pustular psoriasis is well established. It is equally useful in children with these disorders, and the most appropriate dosage appears to be in the region of 0.3,0.4 mg/kg as a single weekly dose. Children generally tolerate oral therapy well. Methotrexate also appears helpful in arresting the progression of linear morphoea, both in the case of coup de sabre lesions and progressive hemi-facial atrophy, and in limb lesions that are interfering with joint mobility or are causing profound lipoatrophy. Intravenous methylprednisolone appears to be of value in several acute dermatoses in childhood, but is most commonly used at Great Ormond Street Hospital in the hope of arresting progression of severe muco-cutaneous erythema multiforme and toxic epidermal necrolysis. Various dose regimens are used in children, but in our unit we use a dose of 20,30 mg/kg per day, up to a maximum of 500 mg, for 3 successive days. Each dose is given over period of 2 h with frequent monitoring of vital signs, particularly blood pressure. [source] A novel therapeutic paradigm to treat congenital hypothyroidismCLINICAL ENDOCRINOLOGY, Issue 1 2008Sarah Mathai Summary Objective, To determine the effectiveness of a novel therapeutic paradigm to treat congenital hypothyroidism (CH) incorporating variable initial doses of L-T4 based on the underlying aetiology and frequent monitoring, up to 2 years of age. Design, Retrospective cohort study. Patients, Infants with primary CH diagnosed by newborn screening. Measurements, Treatment with L-T4 suspension initiated at 10, 12 and 15 µg/kg/day for dyshormonogenesis, ectopia and athyreosis, respectively. Serum TSH and free T4 (FT4) levels monitored weekly during the first 4 weeks, at 6 weeks, thereafter monthly during the first 2 years. Dose changes were made to keep FT4 level in upper half of the normal range. Results, Sixty-nine infants; 17 had dyshormonogenesis, 35 ectopia and 17 athyreosis. Seventy-eight percent of subjects normalized FT4 levels within 7 days of treatment and 100% within 14 days. TSH levels normalized in 26% of infants within 7 days and in 92% by 21 days. Supraphysiological levels of FT4 were noted in 28% of infants, for a maximum of 2 weeks. 48% infants needed one dose adjustment and 30% needed at least two in the first month. In 52 infants over the first 2 years, mean FT4 levels were consistently in the upper half of the normal range. Two or more dose adjustments every 3 months were made 57 times in the first year as compared to 19 times in the second year. Conclusions, A variable initial dose paradigm based on aetiology with frequent testing and using T4 suspension rapidly normalizes FT4 levels without producing persistent hyperthyroxinaemia. [source] Cytomegalovirus in transplantation , challenging the status quoCLINICAL TRANSPLANTATION, Issue 2 2007Jay A Fishman Abstract:, Background:, Cytomegalovirus (CMV) infection of solid organ transplant (SOT) recipients causes both ,,direct'' and ,,indirect'' effects including allograft rejection, decreased graft and patient survival, and predisposition to opportunistic infections and malignancies. Options for CMV prevention include pre-emptive therapy, whereby anti-CMV agents are administered based on sensitive viral assays, or universal prophylaxis of all at-risk patients. Each approach has advantages and disadvantages in terms of efficacy, costs, and side effects. Standards of care for prophylaxis have not been established. Methods:, A committee of international experts was convened to review the available data regarding CMV prophylaxis and to compare preventative strategies for CMV after transplantation from seropositive donors or in seropositive recipients. Results:, Pre-emptive therapy requires frequent monitoring with subsequent treatment of disease and associated costs, while universal prophylaxis results in greater exposure to potential toxicities and costs of drugs. The advantages of prophylaxis include suppressing asymptomatic viremia and prevention of both direct and indirect effects of CMV infection. Meta analyses reveal decreased in mortality for patients receiving CMV prophylaxis. Costs associated with prophylaxis are less than for routine monitoring and pre-emptive therapy. The optimal duration of antiviral prophylaxis remains undefined. Extended prophylaxis may improve clinical outcomes in the highest-risk patient populations including donor-seropositive/recipient-seronegative renal transplants and in CMV-infected lung and heart transplantation. Conclusions:, Prophylaxis is beneficial in preventing direct and indirect effects of CMV infection in transplant recipients, affecting both allograft and patient survival. More studies are necessary to define optimal prophylaxis regimens. [source] Review of select transplant subpopulations at high risk of failure from standard immunosuppressive therapyCLINICAL TRANSPLANTATION, Issue 5 2000Mark H Deierhoi Despite improvements in short-term graft and patient survival rates for solid organ transplants, certain subgroups of transplant recipients experience poorer clinical outcome compared to the general population. Groups including pediatrics, African-Americans, diabetics, cystic fibrosis patients, and pregnant women require special considerations when designing immunosuppressive regimens that optimize transplant outcomes. Problems specific to pediatric transplant recipients include altered pharmacokinetics of immunosuppressive drugs, such as cyclosporine (CsA) and tacrolimus (poor absorption, increased metabolism, rapid clearance), the need to restore growth post-transplantation, and a high incidence of drug-related adverse effects. African-Americans have decreased drug absorption and bioavailability, high immunologic responsiveness, and a high incidence of post-transplant diabetes mellitus. Diabetics and cystic fibrosis patients exhibit poor absorption of immunosuppressive agents, which may lead to underimmunosuppression and subsequent graft rejection. Pregnant women undergo physiologic changes that can alter the pharmacokinetics of immunosuppressives, thus requiring careful clinical management to minimize the risks of either under- or overimmunosuppression to mother and child. To achieve an optimal post-transplant outcome in these high-risk patients, the problems specific to each group must be addressed, and immunosuppressive therapy individualized accordingly. Drug formulation greatly impacts upon pharmacokinetics and the resultant level of immunosuppression. Thus, a formulation with improved absorption (e.g., CsA for microemulsion), higher bioavailability, and less pharmacokinetic variability may facilitate patient management and lead to more favorable outcomes, especially in groups demonstrating low and variable bioavailability. Other strategies aimed at improving transplant outcome include the use of higher immunosuppressive doses, different combinations of immunosuppressive agents, more frequent monitoring, and management of concurrent disease states. [source] | ||||||||||