Changes In Laboratory Test Results Research Articles

Parameters of Complete Blood Count and Blood Chemistry during Treatment of Patients with MDR/XDR Pulmonary Tuberculosis with a Short-Course Regimen Containing Bedaquiline, Pretomanid, and Linezolid

The objective: assessment of changes in the parameters of complete blood count, clinical urine tests, and blood chemistry during chemotherapy of patients with MDR/XDR pulmonary tuberculosis receiving the short-course regimen containing bedaquiline, pretomanid, and linezolid (B-Pa-L).Subjects and Methods. 18 patients with MDR/pre-XDR/XDR pulmonary tuberculosis were enrolled into the study. They all received treatment at Central Tuberculosis Research Institute from 2015 to 2022.Results. In the course of chemotherapy of these patients, changes in laboratory test results were noted at different times. Abnormal changes in complete blood count were detected in 10/18 (55,6%) patients during chemotherapy for the 1st time. Hemoglobin levels, erythrocyte and leukocyte counts decreased. Hematuria and bacteriuria were detected by clinical urine test. Proteinuria was observed in almost in half of the patients. Elevated serum potassium level was frequently noted. Blood chemistry demonstrated elevated levels of ALT and AST, which is typical of cytolytic effect on hepatocytes of drugs within chemotherapy. In most cases, all above abnormalities were degree 1 of toxicity and resolved within 2-4 weeks after they were detected. Abnormalities in grade 2-3 of toxicity were mainly observed in patients receiving linezolid at the dose of 1200 mg/day. In most cases, the above abnormalities were detected during the first 4 weeks of chemotherapy.

Results of the observational program “NOSTALGIA” (new strategies for the treatment of algic syndromes in the lower back in patients with post-COVID syndrome)

Introduction. Allergic syndromes occur in 85.7% of COVID-19 survivors, according to recent statistics. However, there is no clear understanding of the pathogenesis of post-COVID pain syndrome and no therapy algorithms have been developed.Aim. To study the efficacy and safety of Alflutop (the bioactive concentrate from small sea fish (BCSSF)) in COVID-19 survivors with pain syndromes in the lower back (lumbosacral dorsopathy (LSD)) and osteoarthritis (OA)), who were previously treated with other chondroitin sulphate (CS) drugs.Materials and methods. The study group included 50 patients with persistent pain in the lower back according to VAS scale (6.6 ± 1.5 scores) without chronic diseases, pain lasted for more than 1 month. The average age was 55.7 ± 3.5 years, 30 men and 20 women, who had mild or moderate COVID-19 in the period of 40 to 90 days before the study. Some patients had been previously diagnosed with LSD before they contracted COVID-19 and had exacerbations 1-2 times a year. Most of the patients also suffered from large-joint OA. Of all patients, 10 were primary patients (before COVID-19 was diagnosed) and received therapy with non-steroidal anti-inflammatory drugs and CS prior to enrolment in the study. The clinical examination provided to all patients included recording of complaints, medical history, a standard examination of the neurological status at visit 1, 2 (day 14–15), 3 (completion of therapy, 30 days after initiation of therapy) and 4 (2 months after visit 1). The pain was assessed according to VAS, and depression symptoms were measured according to the Hospital Anxiety and Depression Scale. At visit 3, the patients were assessed according to the Clinical Global Impression scale. The standard laboratory test results were analysed.Results. After administration of BCSSF, a pronounced relief of pain and high anxiety was observed in all patients by Day 14. 80% of patients had no pain syndrome without changes in laboratory test results by visit 4. The majority of patients evaluated their condition as good according to the Clinical Global Impression scale.Conclusions. Early administration of BCSSF is topical in the therapy of post-COVID allergic syndromes.

Safety and Efficacy of Paxlovid Against Omicron Variants of Coronavirus Disease 2019 in Elderly Patients.

Elderly patients are the most affected and vulnerable to COVID-19 and effective therapeutic interventions are urgently required. We clarified the safety and efficacy of Paxlovid in the treatment of elderly patients with coronavirus disease 2019 (COVID-19). Patients aged over 60years and with mild to moderate COVID-19 were admitted to the Zhongshan Hospital MinHang MeiLong Branch, Fudan University and received either Paxlovid treatment or only conventional therapy, between April1 and May31, 2022. Viral shedding time, duration of hospital stay, disease progression, and adverse events were analyzed, and multivariate Cox regression analysis was performed to detect the independent high-risk factors for COVID-19 progression in the patients. A total of 163 (82 and 81 in the treatment and control groups, respectively) patients had a median age of 82 (71-89) years, and 89.0% had at least one concomitant disease. The duration of hospitalization reduced from 15 to 13days, and viral shedding time reduced from 20 to 16.5days after Paxlovid treatment. The differences of these two variables between the groups were significant (p < 0.01). Moreover, no serious adverse events or obvious changes in laboratory test results were observed in patients treated with Paxlovid. One patient (1.2%) treated with Paxlovid experienced rebound 56days after negative measurement. Multivariate analysis showed that Paxlovid therapy, age, hemoglobin, and nucleic acid Ct values at admission were independent risk factors for hospitalization within 14days, and the differences were significant (p < 0.01). The use of Paxlovid in elderly patients may promote recovery from COVID-19 and reduce the viral load without adverse events. www. gov , ID: ChiCTR2200066990.

Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A.

AimsDysregulation of histone methylation epigenetic marks may result in intellectual and developmental disability, as seen in Kabuki syndrome. Animal data suggest that increasing histone methylation by inhibiting lysine‐specific demethylase 1A (LSD1) may improve cognitive outcomes in a model of Kabuki syndrome. TAK‐418 is a novel LSD1 inhibitor, developed as a potential therapeutic agent for central nervous system disorders such as Kabuki syndrome. Here, we report safety, tolerability, pharmacokinetic and pharmacodynamic profiles of single and multiple doses of TAK‐418 (ClinicalTrials.gov: NCT03228433, NCT03501069).MethodsTwo randomized, double‐blind, placebo‐controlled, phase 1 studies of oral TAK‐418 were performed, a first‐in‐human single‐rising‐dose (SRD) study (5–60 mg) in healthy adult male and female volunteers (placebo, n = 10; TAK‐418, n = 30), and an SRD (120–160 mg) and multiple‐rising‐dose (MRD) study (20–160 mg once daily for 10 days) in healthy female volunteers (placebo, n = 2 [SRD] and n = 6 [MRD]; TAK‐418, n = 6 [SRD] and n = 18 [MRD]).ResultsTAK‐418 was well tolerated. No clinically significant changes in laboratory test results or vital signs were observed and no serious adverse events were reported. TAK‐418 had a nearly linear pharmacokinetic profile, with rapid absorption and short terminal half‐life across the evaluated dose range. No obvious accumulation was observed after daily administration for 10 days. Administration with food delayed peak plasma concentrations but overall exposure was unaffected. TAK‐418 rapidly crossed the blood–brain barrier and generally showed a dose‐dependent response in the peripheral pharmacodynamic biomarker formyl‐flavin adenine dinucleotide.ConclusionThe brain‐penetrant LSD1 inhibitor TAK‐418 was well tolerated, with pharmacokinetic and pharmacodynamic effects that support further investigation.

Short-Term Variations in Neutrophil-to-Lymphocyte and Urea-to-Creatinine Ratios Anticipate Intensive Care Unit Admission of COVID-19 Patients in the Emergency Department.

Background: Timely assessment of COVID-19 severity is crucial for the rapid provision of appropriate treatments. Definitive criteria for the early identification of severe COVID-19 cases that require intensive care unit admission are lacking.Methods: This was a single-center, retrospective case-control study of 95 consecutive adults admitted to the intensive care unit (cases) or a medical ward (controls) for laboratory-confirmed COVID-19. Clinical data were collected and changes in laboratory test results were calculated between presentation at the emergency department and admission. Univariate and multivariable logistic regression was performed to calculate odds ratios for intensive care unit admission according to changes in laboratory variables.Results: Of the 95 adults with COVID-19, 25 were admitted to intensive care and 70 to a medical ward after a median 6 h stay in the emergency department. During this interval, neutrophil counts increased in cases and decreased in controls (median, 934 vs. −295 × 106/L; P = 0.006), while lymphocyte counts decreased in cases and increased in controls (median, −184 vs. 109 × 106/L; P < 0.001). In cases, the neutrophil-to-lymphocyte ratio increased 6-fold and the urea-to-creatinine ratio increased 20-fold during the emergency department stay, but these ratios did not change in controls (P < 0.001 for both comparisons). By multivariable logistic regression, short-term increases in the neutrophil-to-lymphocyte ratio (OR = 1.43; 95% CI, 1.16–1.76) and urea-to-creatinine ratio (OR = 1.72; 95% CI, 1.20–2.66) were independent predictors of intensive care unit admission.Conclusion: Short-time changes in neutrophil-to-lymphocyte ratio and urea-to-creatinine ratio emerged as stand-alone parameters able to identify patients with aggressive disease at an early stage.

Heart of the World's Top Ultramarathon Runner-Not Necessarily Much Different from Normal.

The impact of ultramarathon (UM) runs on the organs of competitors, especially elite individuals, is poorly understood. We tested a 36-year-old UM runner before, 1–2 days after, and 10–11 days after winning a 24-h UM as a part of the Polish Championships (258.228 km). During each testing session, we performed an electrocardiogram (ECG), transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (MRI), cardiac 31P magnetic resonance spectroscopy (31P MRS), and blood tests. Initially, increased cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were identified. The day after the UM, increased levels of white blood cells, neutrophils, fibrinogen, alanine aminotransferase, aspartate aminotransferase, creatine kinase, C-reactive protein, and N-terminal type B natriuretic propeptide were observed. Additionally, decreases in hemoglobin, hematocrit, cholesterol, LDL-C, and hyponatremia were observed. On day 10, all measurements returned to normal levels, and cholesterol and LDL-C returned to their baseline abnormal values. ECG, TTE, MRI, and 31P MRS remained within the normal ranges, demonstrating physiological adaptation to exercise. The transient changes in laboratory test results were typical for the extreme efforts of the athlete and most likely reflected transient but massive striated muscle damage, liver cell damage, activation of inflammatory processes, effects on the coagulation system, exercise-associated hyponatremia, and cytoprotective or growth-regulatory effects. These results indicated that many years of intensive endurance training and numerous UMs (including the last 24-h UM) did not have a permanent adverse effect on this world-class UM runner’s body and heart. Transient post-competition anomalies in laboratory test results were typical of those commonly observed after UM efforts.

Role of biochemical parameters in predicting histopathological changes at 24 and 48 hours from acute pancreatitis induction

The aim of the study was to assess the relationships between the degree of changes in concentrations of the biochemical indicators in serum such as: creatinine, uric acid, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), lipase, amylase, glucose, iron and magnesium, and histopathological lesions occurring in the pancreas within 24 and 48 hours from the induction of acute pancreatitis (AP). An attempt was made to assess the relation between the changes in concentrations of biochemical indicators and the enhancement of histological lesions in the pancreas based on Spormann score. In the experimental model, the laboratory and histological changes in the 24th hour from administration of taurocholan correspond to the seventh day of the disease in humans. Experiments were conducted on 55 male Wistar rats weighing from 250 g to 300 g. The animals were divided into three groups: Z – a group serving to establish the ranges of studied factors and histological structure; K – a group of animals operated on which were injected with 0.9% NaCl into the biliary-pancreatic duct; E – a group of animals operated on in which acute pancreatitis was induced by an injection of 5% sodium taurocholate into the biliary-pancreatic duct. The material for biochemical and histological examinations was collected after 24 and 48 hours from the induction of AP. Whole pancreases were dissected for histological examinations and the samples were dyed with hematoxylin and saturated alcoholic eosin solution. The degree of pancreatic lesions was assessed according to the Spormann score. Quantitative variables were characterised by arithmetic mean, standard deviation, median, minimum and maximum value and 95% CI. After administration of 0.9% NaCl in the K group, foci of purulent inflammation in the fatty tissue of the pancreas and minor foci of Balser’s necrosis appeared. In the E group, after injection of 5% sodium taurocholate into the biliary-pancreatic duct, more intense lesions were observed: foci of fatty tissue necrosis, hemorrhagic necrosis, multifocal fatty tissue necrosis and inflammatory infiltration. The model was developed in order to assess histological lesions, indicating the character of AP, taking into account edema, inflammatory infiltration, fatty tissue necrosis, glandular necrosis, and ecchymoses. In the period of 24 hours, statistically significant differences between the K group and E group were observed for creatinine, total bilirubin, ALT, lipase, amylase, iron and magnesium, while in the period of 48 hours, statistically significant differences were observed for total bilirubin and ALT. In the group E, in the period of 24 hours concentrations of creatinine, total bilirubin, ALT, lipase, amylase and magnesium were significantly higher than in the group K, but concentrations of iron were significantly lower. In the period of 48 hours, in the E group total bilirubin was significantly lower and ALT was significantly higher than in the K group. In the E group, the intensity of pancreatitis increased together with an increase in ALT concentration in the period of 24 hours; in the period of 48 hours, the intensity of pancreatitis increased together with a decrease in ALT in the E group. In the K group, in the period of 48 hours, intensity of fatty tissue necrosis increased together with a decrease in ALT level. In the period of 48 hours, in the E group intensity of glandular necrosis increased together with a decrease in total bilirubin and AST concentration. In the E group, in the period of 24 hours intensity of edema increased together with an increase in magnesium level. In the period of 48 hours, in the E group intensity of glandular necrosis increased together with a decrease in magnesium or AST level, and the intensity of lesions in the form of ecchymoses increased together with an increase in glucose level. Histopathological lesions occurred prior to changes in laboratory test results, whereas significant correlations with the Spormann score concerned changes in: total bilirubin, AST, ALT, glucose and magnesium. The use of regression analysis with the Spormann score shows statistically significant differences for most of the biochemical parameters in the period of 24 hours correspond to the seventh day of the disease in humans. The presented study results confirm the fact that diagnostics of acute pancreatitis is very difficult and requires monitoring of many laboratory parameters. A search is still going on for an ideal marker of AP which would enable an early prognosis of the progress of the disease and the confirmation of its etiology. A discovery of a simple marker which is cheap to use may turn out to be useful if it is confirmed in prospective studies. The current state of knowledge based on scientific and clinical findings makes it possible to apply interdisciplinary clinical procedures based on matching appropriate laboratory and radiological tests, and on implementing therapeutic procedures...

Risk Factors Affecting Adverse Effects of Cyclosporine A in a Real-World Psoriasis Treatment.

BackgroundNo study to date has focused on the changes in laboratory test results and related risk factors in patients with psoriasis treated with prolonged Cyclosporine A (CsA) therapy.ObjectiveThe objective of this study was to investigate the changes of laboratory values and related risk factors in patients with psoriasis treated with CsA in a real-world setting.MethodsRecords of patients with psoriasis treated with CsA at an outpatient clinic were collected, and a Cox proportional hazards regression model was used.ResultsOf the 128 patients included in this study, 28 patients (21.9%) showed laboratory test abnormalities over a mean medication period of 11.6 months. Older age (hazard ratio [HR], 1.174; 95% confidence interval [CI], 1.068~1.370; p=0.007) and pre-existing kidney disease (HR, 0.008; 95% CI, 0~0.205; p=0.001) significantly increased the risk of renal dysfunction. Male sex was the only significant risk factor for liver enzyme elevation (HR, 0.284; 95% CI, 0.081~0.784; p=0.026) and uric acid abnormality (HR, 0.048; 95% CI, 0~0.372; p=0.046).ConclusionThis is an in-depth analysis of laboratory changes and related risk factors in patients with psoriasis treated with CsA. Liver is the most commonly affected organ of CsA toxicity. Older age, male sex, and presence of kidney disease were risk factors associated with laboratory abnormality during CsA treatment.

Prediction of acute pancreatitis in the earliest stages - role of biochemical parameters and histopathological changes.

To assess the relationship between the extent of change in the concentration of 10 selected biochemical indicators: amylase, lipase, total bilirubin, creatinine, uric acid, aspartate transaminase, alanine transaminase, glucose, magnesium, and iron and histopathological lesions in the pancreas within 2 and 6 hours since induction of AP. The selected time periods correspond to the first and the second day of the disease in people, respectively. The experiments were conducted in 110 male Wistar rats weighing from 250 to 300 g. Experimental animals were divided into three groups: Z - a group in which the ranges of the studied factors and histological structure were established; K - a group of animals operated on which were injected with 0.9% NaCl into the biliary-pancreatic duct; E - a group of animals operated on in which acute pancreatitis was induced by an injection of 5% sodium taurocholate into the biliary-pancreatic duct. Animals from the K and E groups were randomly assigned to one of five subgroups from which the material for biochemical and histological examinations was collected at 2 h and 6 h since the induction of AP. Whole pancreases were dissected for histological examinations, and the samples were dyed with hematoxylin and saturated alcoholic eosin solution. The degree of pancreatic lesions was assessed according to the Spormann score. Quantitative variables were characterized by arithmetic means, standard deviations, medians, minimum and maximum values, and 95% CIs. In histological preparations from rats from the E group, after 2 hours, edematous lesions, neutrophilic infiltrations in the pancreatic parenchyma, together with single petechiae started to appear and were observed. After 6 hours, the lesions became more intense, and minor foci of coagulation necrosis and minor foci of purulent inflammation in the fatty tissue appeared. Within 2 hours, statistically significant differences in the amount of four markers: creatinine, ALT, amylase, and magnesium were observed. After six hours, statistically significant differences in the amount of two markers: AST and glucose were seen. The correlations between histological assessments according to the Spormann scale and biochemical indicators were investigated, and it was observed that within 2 hours the intensity of pancreatitis increased together with an increase in AST. In group K, within 6 hours, the intensity of inflammatory infiltration increased together with an increase in creatinine concentration (correlation coefficient 0.95; p=0.0138). In group E, in the period of 2 hours, lesion intensity in the form of inflammatory infiltration increased together with an increase in the AST level (correlation coefficient 0.90; p=0.0063) and an increase in the iron level (correlation coefficient 0.78; p=0.0399). In the same group and in the same period, an increase in the AST level (correlation coefficient 0.79; p=0.0343) was associated with an increase in lesion intensity in the form of ecchymoses. Inflammatory infiltration increased (correlation coefficient -0.87; p=0.0117) within 6 hours, whereas the creatinine level decreased. Interesting results were obtained with the use of regression analysis - forward stepwise regression. In the period of 2 hours, if the creatinine level increased by 1, the intensity of lesions in acute pancreatitis decreased by 9.02, according to the Spormann score, while the other variables remained at a stable level. However, if ALT level increased by 1, the intensity of lesions in acute pancreatitis increased by 0.02, according to the Spormann score; and if the amylase level increased by 1, the intensity of lesions in acute pancreatitis increased by 0.01, according to the Spormann score, while the other variables remained at a stable level. Histopathological lesions occurred prior to changes in laboratory test results, whereas significant correlations with Spormann scores were seen in the case of changes in AST and creatinine levels. The study results confirm the fact that diagnostics in acute pancreatitis is very difficult and requires monitoring of many laboratory parameters.

Review of a New Multimodal Antidepressant Vortioxetine

Abstract Vortioxetine is a novel antidepressant with two mechanisms of action – direct effect on several serotonin receptors and serotonin re-uptake inhibition. It shows antidepressant, anxiolytic and cognitive effects during the treatment of major depressive disorder (MDD). The aim of this article was to summarize the use of vortioxetine in clinical studies and assess the efficacy and tolerability. Most of the studies reported a statistically significant efficacy for vortioxetine versus placebo. In addition, vortioxetine showed efficacy in patients with an inadequate response to selective serotonin re-uptake inhibitors (SSRI) or serotonin-noradrenaline re-uptake inhibitors (SNRI) monotherapy and improved cognitive function in patients with MDD. In these studies, vortioxetine was well tolerated – most common observed adverse effect was nausea – and it was not associated with clinically important changes in laboratory test results or vital signs. Vortioxetine showed a relatively low incidence of sexual dysfunction.

Human Herpesvirus Type 8-positive Multicentric Castleman Disease.

Castleman disease (CD) is rare lymphoproliferative disorder with local lesionsor with multiple lessions (multicentric CD [MCD]-usually with plasma cell or mix cell morphology). Patients with human herpesvirus (HHV) type 8-positive MCD were included in a separate group owing to its extremely aggressive course and the high risk of transformation into HHV8(+) plasmablastic lymphoma. At our hematologic center, from 1996 to the present, the clinical and morphologic features of 87 patients with CD were analyzed. Immunohistochemical examination revealed DNA HHV8(+) lymph node tissue in patients with plasma cell and mixed cell morphology. In 45 patients, plasma cell or mixed cell variant CD was diagnosed. In 21 patients (8%), the manifestation of CD was local and in 29 (9%), it was multicentric. HHV8 was identified in only 6 cases (23.1%) of MCD (5 men and 1 woman, with a median age of 48.2 years; range, 36-77 years). The median follow-up point was 39.2 months. In 4 patients, the mixed cell variant was diagnosed and in 2, the plasma cell variant was diagnosed. In all the patients, constitutional symptoms, generalized lymphadenopathy, and hepatosplenomegaly were detected. Various laboratory changes were observed, but the most significant were anemia, thrombocytopenia, hypergammaglobulinemia, M-component, increased erythrocyte sedimentation rate, and circulating immune complexes. In 2 cases of HHV8(+) CD, MCD was combined with autoimmune hemolytic anemia and in 2 cases with non-Hodgkin lymphoma. At the last follow-up point, 2 patients were still alive after CHOP (cyclophosphamide, prednisone, Adriamycin, vincristine) and R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], prednisone) therapy with rituximab maintenance. HHV8(+) MCD results in aggressive multiorgan lesions and pronounced changes in laboratory test results. It is characterized by an unfavorable prognosis with a high risk of transformation to plasmablastic lymphoma and a lethal outcome. Timely chemotherapy for patients with HHV8(+) MCD can result in remission and prolong life.

Evaluation of menstrual cycle-related changes in 85 clinical laboratory analytes.

The menstrual cycle-related changes in clinical laboratory values were analysed by use of data obtained in the Asian multicentre study aimed at derivation of common reference intervals for 85 major clinical laboratory tests. Among 1876 healthy female volunteers, 893 had regular menstruation. They were classified into five groups according to dates between sample collection and the start of the last menstrual cycle: early follicular phase (1-6 days), late follicular phase (7-12 days), ovulatory phase (13-16 days), early luteal phase (17-22 days), and late luteal phase (23-31 days). Multiple linear regression analysis was performed to evaluate the menstrual cycle-related changes in test results. The magnitude was expressed as a standard deviation ratio of between-phase standard deviation to between-individual standard deviation based on nested ANOVA. Aside from obvious changes for four sex hormones (oestradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone), we observed statistically significant menstrual cycle-related changes in the following tests (standard deviation ratio >0.15): Na, Cl, creatine kinase, C-reactive protein, serum amyloid A, carbohydrate antigen 125, and parathyroid hormone were higher during the early follicular phase, while insulin, total cholesterol, and white blood cell were higher during the luteal phase. Significant associations of those test items with the four sex hormones were revealed. The menstrual cycle-related changes in laboratory test results were revealed in some commonly tested items other than sex hormones. The findings are of interest in understanding female physiology in relation to hormonal changes, but the magnitude of changes is rather small and not very relevant in interpreting test results.

Using Clinically-Enhanced Claims Data to Discern Current Patterns of Inpatient Care and Identify Opportunities for Improvement

Background: The rapid evolution of electronic medical records presents an opportunity to integrate laboratory and pharmacy order data with administrative claims data to yield an enhanced database. This enhanced database would relate drug administration to admission diagnostic information and changes in laboratory test results. Methods: Administrative claims for 2010-2012 from 16 Minnesota hospitals were enhanced by the electronic pharmacy order and laboratory data. A total of 539 patients admitted for congestive heart failure were grouped by admission creatinine, blood urea nitrogen, and brain natriuretic peptide levels. Descriptive equations were derived relating admission laboratory profiles to two-day administration of furosemide and to corresponding drug administration to 361 patients with good therapeutic responses. Results: Statistically-significant, clinically-plausible relationships between furosemide administration, admission laboratory test results, and therapeutic responses were established. Patients with high admission creatinine levels but lower than threshold BUN-to-creatinine and BNP levels often were receiving suboptimal two-day doses of furosemide. Conclusions: High-quality hospital claims databases enhanced with laboratory and pharmacy order data can be used to characterize current inpatient drug therapy and guide efforts to improve clinical effectiveness.

Protocolo diagnóstico del síndrome de malabsorción intestinal

The optimal diagnostic strategy of malabsorption syndrome is not set. The choice should be individualized and the order of execution of different tests available depending on the suspected etiology. The presentation may vary considerably from steatorrhea and severe weight loss to subtle changes in laboratory test results. As specific tests for suspected global malabsorption, d-xylose guides to the existence of a diffuse intestinal disease. The capital diagnostic test in suspected bacterial overgrowth is the hydrogen breath test after glucose administration. In case of suspected intolerance to carbohydrates, the diagnostic test is lactose tolerance test or hydrogen after administration of lactose.

Randomized, single‐blind, trial of sertraline and buspirone for treatment of elderly patients with generalized anxiety disorder

Generalized anxiety disorder (GAD) in elderly people is common, but few systematic studies regarding the best treatments have been performed. The aim of the present study was to evaluate the efficacy and safety of sertraline and buspirone in the treatment of elderly patients with GAD. Based on selection criteria, 46 patients were recruited who met DSM-IV criteria for GAD. Patients were randomly assigned to sertraline (50-100 mg/day) or buspirone (10-15 mg/day) for 8 weeks in a single-blind trial. The primary outcome measure used in the present study was the Hamilton Rating Scale for Anxiety (HRSA). Both sertraline and buspirone had significant anxiolytic efficacy. A steady decrease in the total HRSA scores for both groups was observed throughout the study period. After 2 and 4 weeks, buspirone was found to be significantly superior to sertraline (P < 0.001), but at the end of study period this difference did not reach statistical significance (P = 0.16). The mean HRSA score after 8 weeks significantly decreased in subjects treated with sertraline (P < 0.001), and buspirone (P < 0.001). No clinically adverse events or changes in laboratory test results were observed during the study period. Both sertraline and buspirone appear to be efficacious and well tolerated in the treatment of GAD in elderly patients. Further studies with larger sample size, evaluating the effect of medical illness, cognitive impairment, depression, and combined therapy with support and psychotherapy are needed.

The Efficacy and Safety of Blonanserin Compared with Haloperidol in Acute-Phase Schizophrenia

Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents. To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia. This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables. All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%). Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.

Effect of Ramelteon, a selective MT1/MT2-receptor agonist, on respiration during sleep in mild to moderate COPD

Ramelteon, a selective MT(1)/MT(2) melatonin receptor agonist, was evaluated in subjects with mild to moderate chronic obstructive pulmonary disease (COPD) to determine whether it would have a negative effect on measures of safety and respiration. This randomized, double-blind, crossover study in 26 subjects with mild to moderate COPD compared the effects of a single bedtime dose of ramelteon 16 mg and placebo on sleep, oxygenation, and sleep-related abnormal breathing events. Compared with placebo, ramelteon had no statistically significant effect on mean arterial oxygen percent saturation (SaO(2)) for the entire night (92.9 vs 92.9%; 95% confidence interval [CI], -0.6 to 0.6; P = 0.972), for each of the 8 h of the night, for each sleep stage (awake, rapid eye movement, nonrapid eye movement) or for the percentage of the night that SaO(2) was less than 85 and 90%. The mean apnea-hypopnea index was similar between ramelteon and placebo groups (9.0 vs 8.3; 95% CI, -1.5 to 3.0; P = 0.515). Polysomnography documented a significant increase in total sleep time (380.6 vs 353.6, P = 0.015), sleep efficiency (79.3 vs 73.7, P = 0.017), and number of awakenings (11.1 vs 9.5, P = 0.036) with ramelteon vs placebo. Other polysomnography and subject-reported sleep measures were comparable between groups. Only one adverse event was reported; it was not considered treatment related. No clinically meaningful changes in laboratory test results, vital signs, electrocardiogram, and physical examination were observed. In this study, ramelteon 16 mg (two times the recommended therapeutic dose) showed no clinically meaningful or statistically significant effects on oxygenation or abnormal breathing events, was well tolerated, and improved sleep duration and efficiency in subjects with mild to moderate COPD.

Clinical Evaluation of Recombinant Factor VIII Preparation (Kogenate) in Previously Treated Patients with Hemophilia A: Descriptive Meta-Analysis of Post-Marketing Study Data

The safety and efficacy of Kogenate, a recombinant factor VIII (rFVIII) preparation for the treatment of bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of Kogenate were evaluated for FVIII inhibitor antibodies, antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11 PTPs investigated (PTP-I) developed antibodies against baby hamster kidney protein and mouse immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855 bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that Kogenate is safe and very effective for the treatment of bleeding in PTPs with hemophilia A.

Safety features of budesonide inhalation suspension in the long-term treatment of asthma in young children

Early inhaled corticosteroid treatment improves symptom control and pulmonary function in children with asthma; however, long-term safety data are limited in infants and young children. This study assessed the long-term safety of budesonide inhalation suspension (BIS) in young children with persistent asthma. To continue to provide BIS to children who needed it-prior to US Food and Drug Administration approval-children 8 years of age or younger with mild, moderate, or severe persistent asthma who previously completed a 52-week open-label study of BIS were enrolled in an additional multicenter, open-label study that was to be concluded upon BIS approval. Patients already receiving BIS continued their current regimens. Patients younger than 4 years and those 4 years of age or older not receiving BIS at baseline started with total daily doses of 0.5 and 1.0 mg, respectively. BIS doses were adjusted throughout the study based on individual response. Adverse events and changes in laboratory parameters, vital signs, and physical examination findings were assessed. Of 198 enrolled patients, 152 (76.8%), 68 (34.3%), and 31 (15.7%) completed 1, 2, and 3 years of BIS treatment (mean daily dose 0.62+/-0.32 mg), respectively. One hundred sixty-six (83.8%) patients experienced an adverse event, of which 8.6% were considered by the investigator to be drug related. Adverse events were those typically occurring in a pediatric asthma population, with respiratory infection (49.0%) and sinusitis (25.3%) occurring at the greatest incidence. Only 2 patients withdrew due to adverse events. Mean changes in laboratory test results and physical examination findings were not clinically important throughout the study. Long-term BIS treatment is well tolerated in young children with persistent asthma, with a safety profile similar to that of short-term administration.

Topical alprostadil cream for the treatment of erectile dysfunction: a combined analysis of the phase II program

Objectives To present a meta-analysis of the efficacy and safety data of two recently completed Phase II studies examining a novel alprostadil topical cream for the treatment of erectile dysfunction (ED). Methods Patients (n = 303) with ED of at least 3 months’ duration were randomized to receive placebo or 50, 100, 200, or 300 μg alprostadil in two nearly identical 11-dose, multicenter, at-home studies of a novel topical cream containing alprostadil and a proprietary skin permeation enhancer. The primary efficacy endpoint was the change in erectile function domain score from baseline to the final visit. Secondary endpoints included changes in scores for questions 3 and 4 of the International Index of Erectile Function and standard diary analyses. Safety was assessed by analysis of adverse events, changes in laboratory test results, and physical examination findings. Results The mean baseline parameters for the erectile function score, ED history, and secondary diagnoses suggested no significant differences among the treatment groups. The changes from baseline to the final visit erectile function scores were 0.98 ± 0.84, 3.4 ± 1.3, 3.4 ± 0.88 ( P <0.05), 5.3 ± 0.92 ( P <0.001), and 9.4 ± 1.43 ( P <0.001) for the ascending dose groups. Most secondary efficacy endpoints were significant for the 200 and 300-μg dose groups. Dose-related trends in efficacy were observed. Adverse events were localized to the application site, were of mild or moderate intensity, and were of short duration. Conclusions These results suggest topical alprostadil cream, when combined with a novel dermal permeation-enhancer, to be a potentially useful agent for the treatment of ED.