Early Drug Therapy Research Articles

Vector of glycated hemoglobin in the formation of dysglycemia in postmenopause: Emphasis on early diagnosis and therapy

Introduction. The close relationship of postmenopause with insulin resistance (IR) and metabolic syndrome (MetS) marks a high cardiometabolic risk of dysglycemia, determining the need for its early diagnosis and therapy. Pathogenetically substantiated criteria for the diagnosis of prediabetes and the nature of early drug therapy for type 2 diabetes mellitus (T2DM) are debated. Information on the relationship between glucose homeostasis parameters and menopausal MetS is fragmentary.Aim. To evaluate the associations of glycated hemoglobin (HbA1c) levels with indices of IR, β-cell function and MetS character- istics in a cohort of postmenopausal women with different carbohydrate metabolic states.Materials and methods. In 94 Caucasian postmenopausal women 58.0 (53.0; 63.0) years old the following were determined: HbA1c, fasting glycemia (FG), TyG and HOMA2 indices, C-peptid, BMI, waist circumference (WC), blood pressure (BP), triglycerides (TG), HDL-C levels. When classifying women by HbA1c (ADA criteria), 15 had normoglycemia, 24 prediabetes, 55 T2DM. ME (25–75%) was assessed using SPSS (version 17); intergroup differences according to the Mann – Whitney test; Spearman and partial correlation analysis were performed.Results. HbA1c age independently correlated with IR parameters: TyG (R = 0.590; p < 0.001), HOMA2-IR (R = 0.318; p < 0.05) and beta cell function: HOMA2-B (R = -0.355; p < 0.001); with lipid markers of MetS (TG, HDL-C, respectively R = 0.382; -0.448; p < 0.001), anthropometric and blood pressure levels.Conclusion. Associations of HbA1c in postmenopausal women with a spectrum of glucose homeostasis parameters and MetS mark it as a vector of formation and progression of dysglycemia due to a close connection with the functional state of β-cells and the importance of lipoglucotoxicity in the dynamics of postmenopausal IR. The obtained data pathogenetically determine the use of HbA1c in the verification of dysglycemia and the early administration of combined antihyperglycemic therapy aimed at preserving β-cell function. The potential of dipeptidyl peptidase-4 inhibitors in slowing the progression of type 2 diabetes mellitus is considered

Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis

ObjectiveTo perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA).MethodsThe...

Natural course of treated epilepsy and medico-social outcomes. Turku studies. Part II

SummaryIntroduction. Population-based data on the prognosis of childhood-onset epilepsy were almost nonexistent in the 1960s. This prompted me to start an epidemiological prospective study on children with epilepsy.Aim. To study the medical and social outcome of children with epilepsy.Methods. The most important personal data on the natural course and outcome were reviewed and compared with the relevant data of other investigators.Results and discussion. The natural course of treated epilepsy is remitting, uninterrupted by relapse (in 48%); a remitting-relapsing course (interrupted by relapses, in terminal remission) (19%); worsening course (early or late remission followed by drug-resistant epilepsy) (14%); and never in ≥5-year remission (drug resistance) (19%) The medical and social outcomes based on my unique, five decades followed cohort show that most subjects are in 10-year remission without medications, which is the definition of resolved epilepsy. Normal or subnormal IQ, non-symptomatic etiology, and low seizure frequency both in the first year of AED treatment and prior to medication appear to be clinical predictors of cure in childhood-onset epilepsy. Subjects with 1-year remission during the first five years form onset of treatment have more than 10-fold chance for entering 5-year terminal remission vs those who have no 1-year remission during the first five years. Even about one fourth of difficult-to-treat subjects become seizure free on medication and more than half of them enter one or more 5-year remissions. Epilepsy has a substantial impact on quality of life even in those who are seizure free off medication for many years and particularly those not in remission or in remission but still on medication.Conclusions. The prognosis is excellent for medical and social outcome. The successful outcome is confirmed by several longitudinal studies from recent decades. Good response to early drug therapy does not necessarily guarantee a favorable seizure outcome, and even a late good response may still predict a successful prognosis. Our life-cycle study is being continued and targets to answer the question whether or not childhood-onset epilepsy is a risk factor for premature and/or increased incidence of mental impairment and dementia.

Acne inversa (Hidradenitis suppurativa): A review with a focus on pathogenesis and treatment

Acne inversa (AI) is a disabilitating chronic inflammatory disease with major negative impact on quality of life and significant co-morbidities. This is an important link to insights into immune dysfunction, which stimulated therapeutic approaches like tumor necrosis-α inhibitor therapy. This new off-label drug treatment is particularly beneficial when used in combination with wide excision of inflamed skin and subcutaneous tissue. Retinoids have been reported to be helpful in secondary prevention. The standard of therapy in advanced cases is surgery with wide excisions and healing by secondary intention. This treatment results in significant reduction of complaints and achieves satisfactory body contouring.

Clinical analysis of 183 cases with infectious keratitis

Objective To analyse the pathogenesis,treatment and result of 183 in-patient with infectious keratitis form January 2004 to December 2009. Methods Clinical manifestations, pathogenesis results was used to clear different corneal infections. Operations and drugs were used to treat these diseases.and results were observed during whole in-patient period. Results All infectious eyes were seen in 179 cases with one eye affected and 4 cases with both eyes affected,the age between 1～80 years,mean age 52. 75 years;male 117 cases( 119 eyes) and female 66 cases(68 eyes). 84 eyes with fungal infection,28 eyes with bacterial infection, 14 eyes with viral infection,5 eyes with mixed infection and 56 eyes with unknown infection;118 eyes received drug treatment (63. 10% ) ,24 eyes received local debridement combined with conjunctival flap microsurgery (12. 83% ), 17 eyes received local debridement combined with amniotic membrane transplantation and conjunctival flap microsurgery (9. 09% ) , 18 eyes received keratoplasty (9. 63% )(16 eyes with penetrating keratoplasty. 2 eyes with lamellar keratoplasty) , 5 eyes received dacryocystorhinostomy (2. 67% ) and 5 eyes with enucleation (2. 67% ). Conclusion Fungal keratitis is the main cause for infectious keratitis; early diagnosis and early drug therapy are effective in most patients, however, some patients need surgery. Key words: keratitis; infectious; keratoplasty; drug therapy

Prehypertension: the Rationale for Early Drug Therapy

Blood pressure within prehypertensive levels confers higher cardiovascular risk by two means. At first, these levels are associated with higher risk for cardiovascular events, starting at BP values as low as 115/75 mmHg, and doubling at each 20 mmHg for systolic or 10 mmHg for diastolic BP. Prehypertension is also an intermediate stage for full hypertension, which develops in an annual rate of 7 out 100 individuals with 40-50 years of age. The precocious drug intervention in patients with prehypertension is therefore appealing. In individuals with previous cardiovascular disease or diabetes the use of BP-lowering agents is compulsory, since the 18-42% reduction of major cardiovascular events demonstrated in randomized clinical trials translates in palpable clinical benefit. In the absence of higher baseline risk, the absolute benefit of treatment is presumably small and was not demonstrated to date. These individuals could be candidate to treatment with the aim to prevent the development of full hypertension. The long-lasting effectiveness of non-drug therapies is low outside the controlled conditions of randomized clinical trials, and there are evidences that the use of BP-lowering drugs reduces the incidence of hypertension in individuals with prehypertension by more than 60%. Clinical trials testing the efficacy and safety of BP agents to prevent hypertension in a population-based perspective are required. In the meantime, it is worthy to present the option to start low doses of BP agents for individuals with prehypertension without co-morbidities who do not respond to the prescription of lifestyle modification.

Residual Urinary Volume and Urinary Tract Infection—When are They Linked?

Large post-void residual urinary volume may be related to the development of urinary tract infection. However, the maximum post-void residual volume that predisposes patients to a higher risk of urinary tract infection is not known. In this prospective study we determined the cutoff value for post-void residual volume that places adult men at risk for bacteriuria. Data were obtained from 196 consecutive healthy adult men (median age 62 years) who came for prostate evaluation without symptoms of acute urinary tract infection. Right after spontaneous voiding, bladder catheterization was performed under normal aseptic conditions, and the post-void residual volume measured. Urine samples were collected for culture from each patient and the results were compared to the various post-void residual volume. Overall 27% of the patients presented with a positive urine culture. The mean post-void residual volume in this group was 257 ml (range 150 to 560) compared to 133 ml (range 10 to 340) for the group with negative culture (p <0.001). The post-void residual volume value of 180 ml was determined to have the best specificity and sensitivity. The positive predictive value for bacterial growth at a post-void residual volume of 180 ml or greater was 87.0% and the negative predictive value was 94.7%. Clinically asymptomatic adult men with a post-void residual volume of 180 ml are at a high risk for bacteriuria. Such cases require close medical attention since it may be necessary to introduce early drug therapy or surgical intervention to improve the bladder emptying.

Thiazolidinediones: The case for early use

Editor’s note: This commentary was originally solicited as part of a Point-Counterpoint feature, but the author of the Counterpoint failed to provide the promised manuscript. Thiazolidinediones (TZDs), or “glitazones,” were first introduced for the treatment of type 2 diabetes in 1996, when troglitazone (Rezulin; Parke-Davis/Warner-Lambert) was approved by the Food and Drug Administration. Since the introduction of this unique class of compounds, many clinicians have embraced their use, whereas others have debated the role of insulin-sensitizing therapy for the management of type 2 diabetes. While troglitazone was withdrawn from the market in 2000 due to idiosyncratic hepatoxicity, two other glitazones, pioglitazone (Actos; Takeda Chemical Industries) and rosiglitazone (Avandia; GlaxoSmithKline), continue to be widely used by clinicians. Before the introduction of glitazones, conventional management of type 2 diabetes involved stepwise addition of medical nutrition therapy, sulfonylureas, and metformin. Despite broader use of early drug therapy, many patients do not achieve adequate blood glucose control (1). Even in those who do achieve treatment targets, a gradual deterioration in blood glucose control is often seen (2). These observations have prompted clinicians to use newer therapies, such as the glitazones, and have increased the use of early combination therapy to achieve glycemic targets Glitazones uniquely target insulin resistance—a core physiologic defect in those with type 2 diabetes—and by so doing significantly improve glucose control. Glitazones improve insulin action in muscle, adipose, and hepatic tissue by acting as agonists of peroxisome proliferator–activated receptor-γ (PPAR-γ) nuclear receptors. Activation of PPAR-γ results in a myriad of both metabolic and vascular effects by upregulating and downregulating expression of numerous genes, including genes known to regulate lipid and glucose metabolism, vascular function, thrombotic function, and the inflammatory response. Glitazones increase nonoxidative glucose disposal, increase triglyceride synthesis, and improve free fatty acid (FFA) metabolism (3). Glitazones also lower blood pressure, …

Thiazolidinediones

Editor’s note: This commentary was originally solicited as part of a Point-Counterpoint feature, but the author of the Counterpoint failed to provide the promised manuscript. Thiazolidinediones (TZDs), or “glitazones,” were first introduced for the treatment of type 2 diabetes in 1996, when troglitazone (Rezulin; Parke-Davis/Warner-Lambert) was approved by the Food and Drug Administration. Since the introduction of this unique class of compounds, many clinicians have embraced their use, whereas others have debated the role of insulin-sensitizing therapy for the management of type 2 diabetes. While troglitazone was withdrawn from the market in 2000 due to idiosyncratic hepatoxicity, two other glitazones, pioglitazone (Actos; Takeda Chemical Industries) and rosiglitazone (Avandia; GlaxoSmithKline), continue to be widely used by clinicians. Before the introduction of glitazones, conventional management of type 2 diabetes involved stepwise addition of medical nutrition therapy, sulfonylureas, and metformin. Despite broader use of early drug therapy, many patients do not achieve adequate blood glucose control (1). Even in those who do achieve treatment targets, a gradual deterioration in blood glucose control is often seen (2). These observations have prompted clinicians to use newer therapies, such as the glitazones, and have increased the use of early combination therapy to achieve glycemic targets Glitazones uniquely target insulin resistance—a core physiologic defect in those with type 2 diabetes—and by so doing significantly improve glucose control. Glitazones improve insulin action in muscle, adipose, and hepatic tissue by acting as agonists of peroxisome proliferator–activated receptor-γ (PPAR-γ) nuclear receptors. Activation of PPAR-γ results in a myriad of both metabolic and vascular effects by upregulating and downregulating expression of numerous genes, including genes known to regulate lipid and glucose metabolism, vascular function, thrombotic function, and the inflammatory response. Glitazones increase nonoxidative glucose disposal, increase triglyceride synthesis, and improve free fatty acid (FFA) metabolism (3). Glitazones also lower blood pressure, …

Early Drug Therapy and In-Hospital Mortality following Acute Myocardial Infarction

Background: Early drug therapy in patients with ST-elevation infarction is essential for improved short- and long-term outcomes. Most of the drugs used currently have been extensively studied in the era prior to reperfusion therapies, and thus it is important to assess the value of these drugs in today’s clinical practice and compare the results with those of randomized trials. Objectives: The study assessed the effects of age, gender, risk factors, reperfusion therapy and early drug therapy in patients with acute myocardial infarction with ST elevation or new left bundle-branch block on in-hospital mortality. Methods: The analysis of drug administration and in-hospital mortality is based on the AMIS Plus project, a registry of acute coronary syndromes in Switzerland since 1997. Data from 7,279 patients admitted to participating hospitals between 1997 and 2002 were analyzed, and the effect of factors and drug therapies on in-hospital mortality was assessed by logistic regression analysis. Results: Age and diabetes were identified as factors associated with a higher likelihood of in-hospital mortality, while a significant and important reduction of in-hospital mortality was due to the use of thrombolytic therapy or primary percutaneous coronary intervention (PCI) [relative risk reduction (RRR) of 31%, odds ratio (OR) and 95% confidence interval: 0.69; 0.54–0.87; p = 0.002 for thrombolysis, RRR of 34%; OR 0.66; 0.44–0.99; p = 0.044 for PCI]. Early administration of aspirin or ADP antagonists is associated with a risk reduction of in-hospital mortality by 36% (OR 0.63; 0.45–0.89; p = 0.009) and 50% (OR 0.49; 0.35–0.70; p < 0.001), respectively. The use of unfractionated heparin did not reduce in-hospital mortality. Administration of ACE inhibitors, nitrates or beta-blockers reduced the relative risk of in-hospital death by 40% (OR 0.60; 0.49–0.75; p = 0.009), 42% (OR 0.58; 0.46–0.72; p < 0.001) and 54% (OR 0.46; 0.37–0.57; p < 0.001), respectively. Less frequent use of reperfusion therapies and beta-blockers was documented for older patients. Gender was not a determining factor for in-hospital survival. Conclusion: Early administration of aspirin or ADP inhibition with ticlopidine or clopidogrel as well as the early use of beta-blockers, nitrates and ACE inhibitors had a beneficial effect on in-hospital mortality in the reperfusion era with either thrombolytics or PCI. The association of a beneficial effect of ADP inhibition was more pronounced than that found in randomized trials for non-ST-elevation infarction. However, it cannot be excluded that patients with a lower risk for in-hospital death who were selected for early invasive assessment received more frequently ADP inhibitors and that this influenced this beneficial effect. Diabetes and age had negative effects on in-hospital mortality, and both reperfusion therapy and beta-blockers were much less frequently used in elderly patients.

Cross-classification of JNC VI blood pressure stages and risk groups in the Framingham Heart Study.

The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are stratified into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (> or =1 associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). To examine the prevalence of risk groups and blood pressure stages in a community-based sample. We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group A, 59.3% were in group B, and 38.2% were in group C. In the high-normal or hypertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. These results provide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice.

Cross-classification of blood pressure stages and risk groups in the framingham heart study

Background: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are stratified into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B ($1 associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). Objective: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. Methods: We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. Results: In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with highnormal blood pressure or hypertension, only 2.4% (all women) were in risk group A, 59.3% were in group B, and 38.2% were in group C. In the high-normal or hypertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. Conclusions: These results provide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice. Arch Intern Med. 1999;159:2206-2212

Patterns of neuroendocrine activation at rest and during exercise following acute myocardial infarction.

Previous studies of neurohumoral activation following myocardial infarction have concentrated on the within-hospital phase and have only made measurements at rest. The objectives of this study were to measure neuroendocrine activity in the early convalescent phase of myocardial infarction at rest and during symptom-limited maximal exercise and to study the effects of early drug therapy. We studied 75 patients, mean age 57 (range 37-74) without evidence of overt heart failure, following Q-wave myocardial infarction. Patients were studied a mean of 17 days following myocardial infarction and compared with 11 age-matched control subjects. Plasma noradrenaline, adrenaline, atrial natriuretic peptide and plasma renin activity were measured at rest, at submaximal and symptom-limited maximal treadmill exercise. At the time of study 40 patients were taking beta-blockers, 19 diuretics and 16 no treatment. Atrial natriuretic peptide levels were higher at rest (P = 0.0001) and at symptom-limited exercise (P = 0.002) in the patient group than in the control subjects. Although there were no significant resting differences between the patient subgroups, at symptom-limited exercise plasma atrial natriuretic peptide levels were significantly higher in the patients taking beta-blockers than in the other patient groups (P = 0.001). Plasma renin activity was no different between the patients and the control subjects at rest or during exercise. Those patients taking diuretics had higher values at rest (P = 0.001) and during exercise (P = 0.005) compared with the remaining patients. There were no significant differences in resting or maximal exercise levels of plasma noradrenaline and adrenaline between the patients and the control subjects (all P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Filariasis

Filariasis is found in many tropical and subtropical countries. Approximately 10% of patients with filariasis enter the end stage of the disease known as elephantiasis. The obstruction of the lymphatic system leads to massive swelling and ulceration, especially of the legs, causing deformity and difficulty in movement and function. The condition is preventable with control of the vector and early drug therapy.

Emergency Department Management of Life-Threatening Arrhythmias

Emergency treatment of life-threatening arrhythmias is related to appreciation of their hemodynamic consequences. In all case, attention should be paid to treating the patient and not merely the electrical rhythm. Emergency cardioversion or defibrillation should be performed in tachyarrhythmias with associated significant end-organ hypoperfusion. Early drug therapy, stabilization, and referral for definitive therapy may be appropriate when tachyarrhythmias do not produce significant hemodynamic consequences. Asymptomatic bradycardia should not be treated emergently but referred for definitive care in those circumstances in which it is necessary. Bradycardia associated with end-organ hypoperfusion should be treated with trials of atropine, or isoproterenol, or emergency pacemaker insertion, and the stabilized patient referred to the cardiac procedure laboratory or cardiac care unit as appropriate. This same approach to bradyarrhythmias applies regardless of the anatomic and electrophysiologic etiology of the decreased heart rate. Attention to these few management principles clearly stresses the primary importance of the hemodynamic effects of any arrhythmia other than the arrhythmia itself.