Correction to: Efficacy and safety of ixekizumab in patients with active psoriatic arthritis with and without concomitant conventional disease-modifying antirheumatic drugs: SPIRIT-P1 and SPIRIT-P2 3-year results

Clinical Rheumatology -     

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.     

Beta blocker overdose with propranolol and with atenolol

During a one-month period, two cases of beta-adrenergic blocker overdose were treated by the emergency staff at our hospital. One case of propranolol intoxication demonstrated profound cardiovascular collapse and generalized tonic-clonic seizures. The condition failed to respond to high-dose intravenous pressor agents, but did improve significantly with IV glucagon infusion. The second overdose involved atenolol. Although the blood levels reported were very high, the patient showed no cardiovascular compromise and required only inhaled bronchodilators for an exacerbation of her asthma.     

Safer colonoscopy with patient-controlled analgesia and sedation with propofol and alfentanil.

BACKGROUND: The aim of this study was to assess the efficacy of patient-controlled analgesia and sedation with propofol/alfentanil for colonoscopy compared with continuous drug infusion and conventional nurse-administered medication. METHODS: One hundred fifty patients undergoing colonoscopy on an outpatient basis were randomly assigned to 1 of 3 medication regimens. To maintain blinding, all patients were connected to an infusion pump. Group I patients could self-administer boluses of 4.8 mg propofol and 125 microg alfentanil without restriction. Group II patients received a continuous infusion with 0.048 mg/kg propofol and 0.12 microg/kg alfentanil per minute. Group III patients received intravenous premedication with 0.035 mg/kg midazolam and 0.35 mg/kg meperidine. RESULTS: There were no differences between the groups with respect to pain (visual analogue scale) and procedure time. Patient-controlled analgesia and sedation with propofol/alfentanil (group I) resulted in less of an increase in the transcutaneous partial pressure of carbon dioxide (p = 0.0004) during colonoscopy and less of a decrease in mean arterial blood pressure (p = 0.0021) during recovery, as well as more complete recovery (p = 0.0019) after 45 minutes compared with conventional administration of midazolam/meperidine. Furthermore, patient-controlled analgesia and sedation yielded a higher degree of patient satisfaction than continuous infusion of propofol/alfentanil (p = 0.0033) or nurse-administered midazolam/meperidine (p = 0.0094). CONCLUSIONS: Patient-controlled administration of propofol and alfentanil for colonoscopy may provide a better margin of safety than conventional administration of midazolam and meperidine and results in a higher level of patient satisfaction and shorter recovery.     

Refractory anemia with ring sideroblasts and RARS with thrombocytosis

Disease Overview : Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS‐T). Diagnosis : RARS is a lower risk myelodysplastic syndrome (MDS) with dysplasia limited to the erythroid lineage, <5% bone marrow (BM) blasts and ≥15% BM RS. RARS‐T is a provisional entity in the MDS/MPN (myeloproliferative neoplasm) overlap syndromes, with diagnostic features of RARS, along with a platelet count ≥450 × 10(9)/L and large atypical megakaryocytes similar to those observed in BCR‐ABL1 negative MPN. Mutations and Karyotype : Mutations in the SF3B1 gene are seen in ≥80% of patients with RARS and RARS‐T, and strongly correlate with the presence of BM RS; RARS‐T patients have additional mutations such as, JAK2V617F (～60%), MPL (<5%), and CALR (<5%). Cytogenetic abnormalities are uncommon in both RARS and RARS‐T. Risk stratification : Most patients with RARS are stratified into lower risk groups by the International Prognostic Scoring System (IPSS) for MDS and the revised IPSS. Disease outcome in RARS‐T is better than that of RARS, but worse than that of essential thrombocytosis. Both RARS and RARS‐T have a low risk of leukemic transformation. Treatment : Anemia and iron overload are complications in both diseases and are managed similar to lower risk MDS. Aspirin therapy is reasonable in RARS‐T, especially in the presence of JAK2V617F, but the value of platelet‐lowering drugs is uncertain. Case reports of RARS‐T therapy with lenalidomide warrant additional studies. Am. J. Hematol. 90:550–559, 2015. © 2015 Wiley Periodicals, Inc.     

Experience with the treatment of patients with hypertrophic cardiomyopathy with obsidan and isoptin

Forty-five patients with hypertrophic cardiomyopathy were examined clinically and echocardiographically. The results of their treatment with obsidan and isoptin in relation to various types of central hemodynamic disorders are presented. The data have been obtained making it possible to treat patients differentially with regard to the form of the disease. The treatment of this category of patients requires the echocardiographic monitoring of the parameters of the central hemodynamics and myocardial contractility.     

Life Events and Stress in Patients with Functional Dyspepsia Compared with Patients with Duodenal Ulcer and Healthy Controls

Background: Life events and stress may be important for functional dyspepsia and duodenal ulcer. Methods: The perception of life events in the preceding 6 months was recorded in 100 patients with functional dyspepsia, 100 patients with duodenal ulcer, and 100 healthy controls. In addition, psychologic and social factors were assessed. Results: Patients with functional dyspepsia experienced significantly more life events than patients with duodenal ulcer and healthy controls. The difference in life events between the groups was due to the difference in stressful life events. The patients with functional dyspepsia had higher levels of state-trait anxiety, general psychopathology, and depression than patients with duodenal ulcer and healthy controls. Conclusion: Patients with functional dyspepsia had higher scores on negative life events than patients with duodenal ulcer and healthy controls. This may be causally related to the higher levels of anxiety, depression, and general psychopathology in these patients.     

Myocarditis and pericarditis with tamponade associated with disseminated tuberculosis

Tuberculous involvement of the myocardium is relatively rare. Tuberculous pericarditis with tamponade and myocarditis in a young woman with no evidence of immunosuppression and disseminated tuberculosis is described. Three distinct forms of myocardial involvement are recognized: nodular tubercles (tuberculomas) of the myocardium; miliary tubercles of the myocardium; and an uncommon diffuse infiltrative type. The myocardium is involved by a hematogenous route, by lymphatic spread or contiguously from the pericardium. The diagnosis can be made by endomyocardial biopsy if clinical suspicion is strong and echocardiographic findings are suggestive. Antituberculosis drugs may be curative. With an increasing prevalence of tuberculosis, the possibility of potentially lethal myocardial tuberculosis is important to consider.     

Multi-system Infection with Nocardia farcinica-therapy with linezolid and minocycline

We describe a case of disseminated infection with a multiple-resistant strain of Nocardia farcinica, probably resulting from direct inoculation during a road traffic accident. Initial presentation was with pulmonary symptoms, with subsequent development of cutaneous, renal, soft tissue and cerebral involvement. Precise microbiological diagnosis was delayed. Once sensitivity test results were available, the patient was stabilised on linezolid and minocycline. Premature withdrawal of therapy at one month resulted in recrudescence of infection, requiring re-institution of treatment. Linezolid was discontinued after a total of 4 months, because of evidence of myelosuppression and visual impairment, which subsequently improved. Monotherapy with minocycline was continued for a total of 12 months. The patient now remains well.     

Prophylaxis with ofloxacin in patients with cancer and neutropenia

Summary The suppression of potentially pathogenic microorganisms using prophylactic antibacterial treatment could eventually protect the patient from infection. Oral absorbable and non-absorbable antibacterial agents have been used with variable results. In the present study, 47 patients with cancer and neutropenia received oral ofloxacin 200 mg twice daily prophylactically. All patients were previously treated with antineoplastic chemotherapy. Septicemia developed in ten patients (21%). The number of infections was higher in patients with a level of granulocytopenia under 0.5×10⁹/l. Infection was caused in almost all patients by gram-positive organisms. Prophylaxis with ofloxacin provided efficacious protection against gram-negative bacteria and was well tolerated.

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Prophylaxe mit Ofloxacin bei neutropenischen Patienten mit Krebs

Zusammenfassung Die Unterdrückung potentiell pathogener Mikroorganismen durch antibakterielle Prophylaxe kann den Patienten möglicherweise vor einer Infektion schützen. Oral absorbierbare und nicht absorbierbare antibakterielle Substanzen wurden mit wechselnden Ergebnissen eingesetzt. In der vorliegenden Studie wurden 47 Krebspatienten in der neutropenischen Phase 200 mg Ofloxacin zweimal täglich oral verabreicht. Alle Patienten hatten vorher eine antitumorale Chemotherapie erhalten. Bei zehn Patienten (21%) entwickelte sich eine Sepsis. Bei Patienten mit Granulozytenzahlen unter 0,5×10⁹/l traten Infektionen häufiger auf. Bei fast allen Patienten wurden die Infektionen durch grampositive Erreger verursacht. Die Prophylaxe mit Ofloxacin bot einen wirksamen Schutz gegen gramnegative Infektionen und wurde gut vertragen.

     

Hypocalcemia and hypercalcemia in patients with rhabdomyolysis with and without acute renal failure

Patients with rhabdomyolysis (RBD) and acute renal failure (ARF) are hypocalcemic during the oliguric phase of ARF and over 30% develop hypercalcemia during the diuretic phase. The present study examined the factors underlying these derangements in calcium metabolism in 15 patients: 7 with RBD and ARF, 4 with RBD only, and 4 with ARF only. All patients had hypocalcemia on admission and the hypocalcemia was more pronounced in those with RBD and ARF. All patients with RBD independent of the presence or absence of ARF had calcium deposition in soft tissues as documented by technetium-99 scan. In 4 patients with RBD and ARF, hypercalcemia developed during the diuretic phase at a time when Serum PTH levels were undetectable. Only patients with RBD and ARF had a significant increase in serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D [1,25(OH)2D] during the diuretic phase and both the increments in and the levels of 1,25(OH)2D were significantly greater in those who were hypercalcemic. The data indicate that 1) hypocalcemia occurs in RBD independent of ARF and is most likely related to calcium deposition in injured tissues, and 2) elevation in serum levels of 1,25(OH)2D plays an important role in the genesis of hypercalcemia during the diuretic phase of patients with RBD and ARF. Our observations suggest that extrarenal production of 1,25(OH)2D may occur in these patients, and/or that the renal production of 1,25(OH)2D may not be so tightly controlled as it is in normal subjects.     

Prolonged responses in patients with MDS and CMML treated with azacitidine and etanercept

Combination therapy with azacitidine and etanercept was hypothesized to lead to improved responses in myelodysplastic syndrome (MDS) patients. Thirty‐two patients with MDS/chronic myelomonocytic leukaemia were treated with azacitidine + etanercept; 30 completed at least three therapy cycles. At 3 months, nine patients had achieved complete response (CR), two had partial response, 10 had marrow CRs, seven had stable disease, two patients had haematological improvement without marrow response and two patients had disease progression. The overall response rate was 72%; median duration of response was not reached at 2 years. Marrow response rates and duration were improved with azacitidine + etanercept compared to azacitidine alone.     

Women with gout: efficacy and safety of urate-lowering with febuxostat and allopurinol

Objective

To compare the characteristics of female versus male gout patients and assess urate‐lowering efficacy and safety of febuxostat or allopurinol treatment in women with gout.

Methods

This was a retrospective analysis of 4,101 hyperuricemic (serum urate [sUA] level ≥8.0 mg/dl) gout subjects enrolled in 3 phase III comparative trials and randomized to receive placebo, febuxostat (40 mg, 80 mg, 120 mg, or 240 mg daily), or allopurinol (100 mg, 200 mg, or 300 mg daily, based on renal function). Baseline demographics and characteristics were summarized and compared between female and male subjects. Urate‐lowering efficacy, which was defined as the proportion of subjects with sUA levels <6.0 mg/dl at final visit, was assessed for all subjects and, among women, according to baseline renal function.

Results

Female gout subjects (n = 226) were older with significantly higher rates of obesity and metabolic and cardiovascular comorbidities than their male counterparts. The percentage of female subjects with sUA levels <6.0 mg/dl at final visit was 0% in the placebo group, 54.3%, 85.1%, 81.0%, and 100.0% in the febuxostat 40 mg, 80 mg, 120 mg, and 240 mg groups, respectively, and 45.9% in the allopurinol group. Similar patterns of urate‐lowering efficacy rates were observed when stratified by renal function. Among all the female subjects, febuxostat 80 mg was significantly more efficacious than allopurinol (P < 0.001). Rates of adverse events (AEs) were low. The most frequently reported AEs were upper respiratory tract infections, musculoskeletal/connective tissue disorders, and diarrhea.

Conclusion

These data suggest that febuxostat 80 mg may be more efficacious than commonly prescribed doses of allopurinol in female gout subjects with high rates of comorbidities.     

Treatment of metastatic renal cancer with ifosfamide and mesnum with and without irradiation

Ifosfamide (50-60 mg/kg of body weight, Days 1-5) and mesnum (10-12 mg/kg of body weight, Days 1-5) were given to 15 patients with measurable metastatic renal cancer. This treatment was repeated on Day 29. In addition, six of these 15 patients received irradiation to some of the metastatic areas. There was one partial remission among 11 evaluable patients after two ifosfamide courses. The partial remission was seen in a metastatic area treated with low-dose irradiation prior to the first ifosfamide course. Two cases of early death and two cases of toxic death (urotoxicity) were observed. The main hematologic complication was moderate to severe leukopenia. Previously reported high response rates to ifosfamide treatment of renal cancer could not be confirmed.     

Mapping quantitative traits with random and with ascertained sibships

Use of a robust score statistic based on a variance components model to map quantitative trait loci in randomly sampled pedigrees is reviewed. Sibships ascertained through a single proband are discussed. Under a standard assumption of multivariate normality, two suggested methods of ascertainment correction are shown to be asymptotically equivalent when the number of sibships is large.