Negative effect of lockdown on juvenile idiopathic arthritis patients

Clinical Rheumatology - The aim of this study is to evaluate a possible negative action of lockdown, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, in the...     

The use of MALDI-TOF ICMS as an alternative tool for Trichophyton rubrum identification and typing

Aims

In this study, the potential of matrix-assisted laser desorption/ionization time-of-flight intact cell mass spectrometry (MALDI-TOF ICMS) was investigated for the identification of clinical isolates. The isolates were analyzed at the species and strain level.

Methods

Spectral identification by MALDI-TOF ICMS was performed for all strains, and compared with the results of sequencing of the internal transcribed spacers (ITS1 and ITS2), and the 5.8S rDNA region. PCR fingerprinting analysis using primers M13, (GACA)₄, and (AC)₁₀ was performed in order to assess the intra-specific variability of Trichophyton rubrum strains.

Results

The identification of strains at species level by MALDI-TOF ICMS was in agreement with the previously performed morphological and biochemical analysis. Sequence data confirmed spectral mass identification at species level. Intra-specific variability was assessed. Within the T. rubrum cluster, strains were distributed into smaller highly related sub-groups with a similarity values above 85%.

Conclusions

MALDI-TOF ICMS was shown to be a rapid, low-cost and accurate alternative tool for the identification and strain typing of T. rubrum.     

Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy

BACKGROUND: Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy. METHODS: Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study. RESULTS: Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups. CONCLUSIONS: Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.     

A novel RNASEH2B splice site mutation responsible for Aicardi–Goutieres syndrome in the Faroe Islands

Aim: The aim of the study was to identify the genetic background for Aicardi–Goutieres syndrome (AGS) in the Faroe Islands. Methods: Four patients with AGS were identified. The patients had a variable phenotype, from a severe prenatal form with intrauterine foetal death to a milder phenotype, albeit still with an early onset, within the first 2–3 months. Results: A genome‐wide search for homozygosity revealed one single 15.6 Mb region of homozygosity on chromosome 13, which included RNASEH2B, where a splice site mutation c.322‐3C>G was identified. Screening of 170 anonymous Faroese controls revealed a carrier frequency of approximately 1.8%, corresponding to an incidence of AGS in the Faroe Islands of around 1 in 12 300. Conclusion: The previously identified RNASEH2B mutations comprise altogether 20 mutations (missense, nonsense and splice site) with all patients harbouring at least one missense mutation. The severe phenotype of the Faroese patients compared with the previously reported patients with RNASEH2B mutations may be caused by the presence of two null alleles (although some residual normal splicing cannot be ruled out), whereas patients with one or two missense mutations may have some, albeit abnormal, RNASEH2B proteins, and hence some residual activity of RNASEH2B, explaining their milder phenotype.     

A Comprehensive Map of CNS Transduction by Eight Recombinant Adeno-associated Virus Serotypes Upon Cerebrospinal Fluid Administration in Pigs

Cerebrospinal fluid administration of recombinant adeno-associated viral (rAAV) vectors has been demonstrated to be effective in delivering therapeutic genes to the central nervous system (CNS) in different disease animal models. However, a quantitative and qualitative analysis of transduction patterns of the most promising rAAV serotypes for brain targeting in large animal models is missing. Here, we characterize distribution, transduction efficiency, and cellular targeting of rAAV serotypes 1, 2, 5, 7, 9, rh.10, rh.39, and rh.43 delivered into the cisterna magna of wild-type pigs. rAAV9 showed the highest transduction efficiency and the widest distribution capability among the vectors tested. Moreover, rAAV9 robustly transduced both glia and neurons, including the motor neurons of the spinal cord. Relevant cell transduction specificity of the glia was observed after rAAV1 and rAAV7 delivery. rAAV7 also displayed a specific tropism to Purkinje cells. Evaluation of biochemical and hematological markers suggested that all rAAV serotypes tested were well tolerated. This study provides a comprehensive CNS transduction map in a useful preclinical large animal model enabling the selection of potentially clinically transferable rAAV serotypes based on disease specificity. Therefore, our data are instrumental for the clinical evaluation of these rAAV vectors in human neurodegenerative diseases.     

Reactivation of overt and occult hepatitis B infection in various immunosuppressive settings

The aim of the study was to evaluate clinical and virological differences in HBV reactivation between patients with overt and occult HBV infection. Twenty-three consecutive patients with symptomatic HBV reactivation occurring during or after immunosuppressive therapy were enrolled in a retrospective study: 10 with reactivation of overt HBV infection (overt group) and 13 of occult HBV infection (occult group). Twenty-one patients were treated with nucleot(s)ide analogues after HBV reactivation. Regimens including rituximab or fludarabine were administered more frequently in the occult group (61% vs. 31%, respectively). HBV reactivation was severe frequently in the overt (40%) and occult groups (38.4%). Patients in the overt group showed higher HBV-DNA titers (1.1 × 10(8) ± 1.4 × 10(8) vs. 5.1 × 10(5) ± 6.8 × 10(5) IU; P < 0.005). Seven patients died during HBV reactivation, two in the overt and five in the occult group. Of these seven patients, two remained untreated and five had been treated with Lamivudine; of the 16 patients showing remission of HBV reactivation, four had been treated with Lamivudine, four with Entecavir, two with Telbivudine, and six with Lamivudine plus Adefovir. It is concluded that HBV reactivation is life-threatening in patients with diseases inhibiting the immune response and/or receiving immunosuppressive drugs. Supportive therapy without antiviral drugs or Lamivudine monotherapy may not be effective for treating patients with HBV reactivation.     

Pharmacovigilance implementation and operational conditions in the pharmaceutical industry in São Paulo State, Brazil

The development of new drugs and limitations of clinical trials have increased the likelihood of adverse drug events. Pharmacovigilance is essential to detect and evaluate adverse drug events, thereby reducing risks and avoiding excessive public health costs. This study focused on the pharmacovigilance programs in the pharmaceutical industry in S?o Paulo State, Brazil. Data were collected through questionnaires sent electronically to 105 companies, 41.9% of which responded. The main reason for implementing pharmacovigilance programs was to comply with legal requirements, while the main justification for its absence was production limited to herbal remedies, officinal products, and supplements. The article discusses the obstacles to program implementation, resources used, and characteristics of several such programs. Conclusions: (a) standardization is the reason for the increasing number of programs and reports, but more specific guidelines are needed; (b) results depend on multi-sector involvement; (c) customer service centers are an important source of reports; and (d) operation of the service requires only modest human and material resources.     

Generic drug policy implementation in Brazil

A generic drug policy has been implemented in Brazil since 1999. Several political and administrative stages transpired between enactment of the legislation and the actual marketing and consumption of these drugs. This article describes the policy implementation process and examines the country's generic drug legislation, approved from 1999 to 2002. To contextualize these measures, the study compares articles published by two national periodicals and interviews with a government representative involved in drafting the legislation and a representative from the pharmaceutical industry. Generic drugs quickly gained considerable space in the Brazilian pharmaceutical market. Ongoing adaptation of the legislation, media support, and the government's involvement in spreading the policy were key success factors. The population's access to medicines did not increase significantly, but people can now purchase medicines at more affordable prices and with quality assurance and interchangeability.