Epidemiological survey of hyperuricemia as an adverse reaction to antituberculous therapy with pyrazinamide

PURPOSE: Pyrazinamide is an antituberculous drug that is administered as a two-month course during treatment of pulmonary tuberculosis. Adverse reactions to pyrazinamide have been reported to include hyperuricemia. We performed a retrospective multicenter epidemiological survey to assess the relationship between various patient characteristics and the uric acid level, the changes of uric acid during pyrazinamide administration, and the use of medications for uric acid control as well as attacks of gout or arthralgia at the onset of hyperuricemia. A total of 226 patients who were admitted to four hospitals with pulmonary tuberculosis between January and December 2006 and received short-term intensive pyrazinamide therapy were studied. RESULTS: There were 172 men and 54 women with an average age of 59.5 years and an average body mass index of 19.8 kg/m2. The average serum uric acid concentration before pyrazinamide treatment was 4.73 +/- 1.78 mg/dl, while the average uric acid level after pyrazinamide treatment was 10.63 +/- 2.67 mg/dl, which was significantly higher than the pretreatment level (p<0.0001). During treatment, hyperuricemia (Serum uric acid > or = 8 mg/dl) was reported in 84.5% of patients and arthralgia developed in 4.42%. Although the therapy instituted in 51 patients (22.57%) had to be interrupted or discontinued due to liver dysfunction and skin rashes, which were probably caused by isoniazid and rifampicin, no patient ceased taking pyrazinamide due to an increase of uric acid. Drugs for uric acid control were administered to 21 patients (9.29%). Pyrazinamide is an important agent for intensive short-term antituberculous therapy. Hyperuricemia due to this drug can be managed by observation and does not require interruption of administration.     

A retrospective study evaluating the tolerability and effectiveness of adjunctive antihypertensive drugs in patients with inadequate response to initial treatment

Real‐world tolerability and effectiveness of nebivolol as first add‐on therapy were compared with hydrochlorothiazide, metoprolol, and amlodipine. Medical records of hypertensive adults initiating nebivolol, hydrochlorothiazide, metoprolol, or amlodipine as first add‐on therapy between December 16, 2010 and July 21, 2011 were retrospectively abstracted (N = 1600; 400/treatment). Outcomes included medication‐related side‐effect rates and blood pressure (BP) reduction and control. Compared with nebivolol, metoprolol and amlodipine had significantly higher side‐effect rates (incidence rate ratio [95% CI]: 1.82 [1.14‐2.92] and 2.67 [1.69‐4.21]), respectively); the hydrochlorothiazide‐nebivolol rate ratio was not significant (1.61 [0.95‐2.71]). All treatments reduced BP at 2 months. Metoprolol, amlodipine, and hydrochlorothiazide were associated with significantly lower odds of achieving 2‐month BP control than nebivolol (odds ratios [95% CI]: 0.34 [0.23‐0.51], 0.51 [0.35‐0.75] and 0.66 [0.44‐0.99], respectively). In a real‐world setting, nebivolol as first add‐on therapy was associated with fewer side effects than metoprolol or amlodipine and with a higher BP control rate than hydrochlorothiazide, metoprolol, or amlodipine.     

Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation

Objectives

The purpose of the current study was to assess the effect of angiotensin-converting enzyme inhibitor (ACEI) therapy in facilitating cardioversion from persistent atrial fibrillation (AF) and maintaining sinus rhythm.

Background

Pharmacologic therapy and electrical cardioversion for AF are often unsuccessful in maintaining long-term sinus rhythm.

Methods

The current study, a 1-year, prospective follow-up, comprised 47 patients with persistent AF undergoing electrical cardioversion. Patients receiving ACEI were compared with those receiving other medications. The study end point was the number of defibrillation attempts required for atrial defibrillation and the number of hospital admissions. A secondary end point was change in signal-averaged P-wave duration (SAPD) 1 year after successful electrical cardioversion.

Results

Of those admitted and requiring electrical defibrillation, the number of defibrillation attempts required for successful cardioversion was significantly less in the ACEI group (P < .001). The incidence rate ratio for admissions comparing recipients of ACEI with others was 0.14 (P = .03). Patients receiving ACEI therapy had significantly lower SAPD at 1 year when compared with the no-ACEI group (135 ms ± 3 vs 150 ms ± 2, P = .002).

Conclusions

The use of long-term ACEI therapy facilitated electrical defibrillation in patients with persistent AF. ACEI therapy also reduced SAPD, suggesting amelioration of the arrhythmogenic substrate. Furthermore, we confirmed that SAPD is prolonged in patients with persistent AF.     

老年肺结核合并糖尿病对抗结核药物耐受性的探讨

目的 探讨老年患者对抗结核药物的耐受性和用药原则。方法 对96例老年肺结核中糖尿病组47例与对照组49例使用抗结核药物后出现的副反应进行对比分析。结果 两组男性抗结核药物副反应发生率均高于女性,血糖水平的高低与总的抗结核药物副反应的发生无明显相关性,但糖尿病组第八对颅神经损伤率明显高于对照组。两组抗结核药物副反应均以胃肠反应及肝损为主,其次为第八对颅神经损伤。结论 老年患者抗结核药物剂量应适当减少,慎用或不用氨基糖苷类药物,尤其是合并糖尿病者使用氨基糖苷类药物更易出现第八对颅神经损伤,使用时应严密观察。     

Prediction for effectiveness of steroid pulse therapy by MRI in Graves' ophthalmopathy]

Fifteen patients with Graves' ophthalmopathy (GO) were treated with intravenous methylprednisolone (steroid pulse therapy, 1g daily for 3 days a week, 2-4 times) and followed up by ophthalmological assessment and magnetic resonance imaging (MRI). The signal intensity of enlarged eye muscle and retrobulbar fat was examined with MRI at 0.5T with short inversion time inversion recovery (STIR) sequences. The signal intensity of eye muscle and retrobulbar fat tissue in STIR was evaluated as the ratio to cerebral substantia alba (signal intensity ratio). The thickness of enlarged eye muscle was measured by T1-weighted coronal images. The signal intensity ratios of enlarged eye muscle of GO patients were significantly higher than those of eight normal subjects. Although the signal intensity ratios of muscle and retrobulbar fat before therapy were not related to the severity of clinical findings of GO assessed by ophthalmopathy index, the initial signal intensity ratios of eye muscle and retrobulbar fat of ten patients with improved clinical findings of GO after steroid pulse therapy tended to be higher than those of five patients without improvement by the therapy. After the therapy the signal intensity ratios of muscle and retrobulbar fat were significantly decreased in ten patients with favorable response. Our data suggested that high signal intensity in STIR may reflect edema caused by acute inflammation associated with GO. In conclusion, MRI may be a useful tool for determining the indication and prognosis of steroid pulse therapy. We strongly recommend measuring the signal intensity of eye muscle as well as muscle thickness in MRI to evaluate the activity of GO.     

Efficacy of combination of intravenous cyclosporin A and steroid therapy versus prolonged intravenous steroid therapy alone in patients with severe ulcerative colitis refractory to initial intravenous steroid therapy]

BACKGROUND/AIMS: Maximal duration of intravenous (IV) corticosteroid (CS) treatment and efficacy of cyclosporin A (CsA) have not been clarified for patients with severe ulcerative colitis. We aimed to evaluate and compare the effectiveness of CS and CsA combination therapy with prolonged CS therapy alone in patients with severe UC refractory to initial CS therapy. METHODS: We retrospectively reviewed the medical records of 84 episodes of severe UC in 59 patients between April 1999 and May 2005. RESULTS: Among 84 episodes with IV CS therapy, 45 (53.6%) experienced an early response, while 39 (46.4%) did not respond within 2 weeks. The remaining 36 episodes excluding 3 which underwent colectomy were assigned to either combination therapy of IV CS and CsA or prolonged IV CS treatment alone for additional 2 weeks. Twelve of 16 episodes (75.0%) responded to therapy with combinations of IV CsA and CS, and 16 of 20 episodes (80.0%) to prolonged IV CS treatment alone. There was no statistical difference in response and colectomy rate after 4 weeks between CsA-use group and CsA-non-use group (p=1.00). CONCLUSIONS: These results suggest that CS and CsA combination has no additional benefit over prolonged CS therapy alone in terms of short-term response and that CS can be safely prolonged even after the first 14 days of treatment for severe UC.     

TSH receptor antibody in hyperthyroid patients due to Graves' disease treated with antithyroid drugs]

As an immunologic process, TSH receptor antibody (TRab) may be synthesized by the lymphocytes within the thyroid gland. Two techniques were devised to express this TRap activity: a) thyroid stimulating immunoglobulin (TSI) expressed as thyroid c AMP synthesis and b) TSH binding inhibiting immunoglobulin (TBII) expressed as TSH displacement. In general, serum TSI and TBII activity correlated well with each other in hyperthyroid patients. Measurement of TSI and TBII is useful to assess improvement of immunologic abnormality induced by antithyroid drugs. The data so far gathered indicated that TRab disappears from the blood in about 70-80% of hyperthyroid patients in response to antithyroid drugs. However, this does not indicate that intrathyroidal TRab synthesis has ceased, since thyroglobulin is still secreted supernormally and T3 fails to suppress the thyroid in some patients. On the other hand, normalization of thyroglobulin and absence of TRab in the blood indicated complete normalization in the patients as evidenced by positive T3 suppressibility. By using a number of new drugs, further efforts must be made to completely normalize immunologic abnormality in 100% of patients. Recurrence of hyperthyroidism of Graves' disease is generally associated with re-appearance of TRab in the blood in most of the recurrent patients after discontinuation of antithyroid drugs.     

New trends in patient management: risk-based therapy for febrile patients with neutropenia.

Standard management of febrile neutropenia includes the prompt administration of empirical, broad-spectrum, parenteral antibiotic therapy. This is generally done in a hospital-based setting. Although effective (overall survival of >90%), such therapy leads to prolonged hospitalization, excessive resource utilization, and increased costs. Recently, risk-assessment models have been developed that reliably differentiate febrile patients with neutropenia that are at low risk for morbidity and/or mortality. This has enabled clinicians to administer risk-based treatment to such patients. High-risk patients still receive standard, hospital-based, parenteral treatment. Many patients, however, defervesce promptly and can be discharged home with parenteral or oral antibiotics. Low-risk patients need not be hospitalized at all and can be safely treated with parenteral or oral antibiotics in the outpatient or home setting. Careful risk assessment and patient selection, appropriate antimicrobial regimen(s), and meticulous monitoring for response or the development of complications or toxicity are essential for the success of risk-based therapy.     

The effectiveness of psychorelaxation therapy in patients with hypertension

A study of 117 patients with labile essential hypertension before as well as 6 weeks and 12 months after psychorelaxation treatment (PRT), making use of autogenous training, biological feedback or respiratory relaxation training techniques (the main group), and the control patients, exposed to no psychological effects and those on the so-called psychological placebo, demonstrated a significantly greater fall of systolic and diastolic arterial blood pressure, total peripheral resistance and hypertensive response to emotional stress, as well as better psychological adaptation, quality of life and working capacity in the main-group patients, as compared to the controls, by the end of the study.     

The effectiveness of ustekinumab and vedolizumab as third-line biologic therapy in patients with Crohn's disease

BackgroundThe effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear.AimsWe performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD.MethodsData of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).Results143 patients (UST: n = 113; VDZ: n = 30) were included. At the end of induction, the rates of clinical response (CR) were 61.9% for UST and 60.0% for VDZ (p = 1.00), with steroid-free clinical remission (SFCR) achieved in 38.1% of patients in the UST group and 43.3% of patients in the VDZ group (p = 0.75). After 52 weeks of observation, the rates of CR were 65.9% for UST and 71.4% for VDZ (p = 0.77), while the rates of SFCR were 51.8% for UST and 57.1% for VDZ (p = 0.78). At multiple Cox proportional hazard regression model, age (HR 0.98; p = 0.04) and need for systemic steroids at baseline (HR 3.29; p = 0.003) were found to be independent predictors of treatment discontinuation.ConclusionsBoth VDZ and UST showed high effectiveness as third-line biologic therapy in CD, without significant differences between them.     

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND--Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS--A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS--The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS--Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.     

Pharmacodynamics and pharmacokinetics of antibacterial drugs in the management of febrile neutropenia

We review experimental and clinical data on the pharmacokinetics and pharmacodynamics of antibacterial drugs in febrile neutropenic hosts. Since major pharmacokinetic changes have been reported for various classes of antibiotics in these patients, we advocate the need for adequate initial dosing regimens in all cases. Monitoring drug serum concentrations is mandatory for aminoglycosides and glycopeptides, and special attention should be paid to the dosing frequency of the short half-life beta-lactams to optimise the management of febrile neutropenia, especially in patients with severe sepsis.     

Safety and efficacy of molgramostim as an adjunctive therapy in critically ill patients with severe sepsis

The aim of this uncontrolled, prospective, clinical study was to investigate the efficacy and safety of molgramostim administration in patients with severe sepsis. The subjects were 20 critically ill, mechanically ventilated patients with severe sepsis in a university intensive care unit (ICU). Molgramostim 300 microg s.c. was given every 12 h for 3 d. Treatment for severe sepsis was also administered as medically indicated. No adverse events (clinical or serum chemistry) were considered as drug related. Temperature (p = 0.334) and PaO2/FiO2 index (arterial oxygen tension/inspiratory oxygen fraction) (p = 0.178) were not significantly changed. Total leukocyte and neutrophil count increased significantly (p < 0.001) during drug administration. Simplified Acute Physiology Score II (SAPS II) was not significantly increased (p = 0.955), but there was a statistically significant decrease (p = 0.006) in Sepsis-related Organ Failure Assessment (SOFA) score. Death probability was not statistically different compared with mortality rate on day 28 and overall mortality (p = 0.238 and 0.700, respectively). There were statistically significant decreases (p < 0.01) in serum tumor necrosis factor-alpha (TNF-alpha), TNF-RII and interleukin-2 (IL-2), and an increase in TNF-RI levels between study entry and day 3. Mean ICU stay was 40.2 +/- 7.7 d. In conclusion, molgramostim administration may not affect serum chemistry and PaO2/FiO2 index, may decrease SOFA score but does not produce significant clinical benefit in terms of patients' outcome compared with death probability. It may also influence TNF-alpha, TNF-RI and TNF-RII serum complex levels. These changes may be attributed to the natural clinical course of sepsis or therapy applied.