Eficiencia del estudio alergológico en el diagnóstico de reacciones a beta-lactámicos / Efficiency of the allergological study in the diagnosis of allergic reactions to beta-lactams

Objetivos Valorar qué proporción de pacientes etiquetados como alérgicos β-lactámicos siguen teniendo dicha etiqueta en su historial médico tras realizarles un estudio alergológico, a qué proporción de los no alérgicos se les volvió a recetar uno de estos antibióticos y si el estudio alergológico es rentable. Métodos Est udio retrospectivo entre 2019 y 2021 en el que valoramos los pacientes por sospecha de alergia a β-lactámicos (n=688). A través del estudio alergológico se aclaró si tenían dicha alergia. Posteriormente, se revisó si continuaba constando la etiqueta de alérgico en el historial médico. A través de la prescripción digital en la tarjeta sanitaria se ha observado si se les volvió a recetar dicho antibiótico tras el estudio y si lo retiraron de la farmacia. Resultados Un 11,3% de pacientes presentaban hipersensibilidad a β-lactámicos. Sin embargo, en un 33,1% de pacientes continuaban presentando la etiqueta de alérgicos en su historial médico a pesar de no serlo. En un 32% de pacientes en los que se había confirmado la alergia tenían la etiqueta de alérgicos en su historial sin revisar por su médico de atención primaria y en un 32,8% se les había recetado de nuevo un β-lactámico. Conclusiones Es igual de importante descartar la alergia a dichos antibióticos como modificar la etiqueta de alérgico en su historial médico tras el estudio. Una proporción de no alérgicos siguen constando como alérgicos tras el estudio. Estar etiquetado como alérgicos a los β-lactámicos tiene consecuencias a corto y largo plazo tanto para el propio paciente como para el gasto sanitario. (AU)

Aims Assessing the rate of β-lactams-allergic patients who are still labelled as such in their medical records after being performed an allergic test; as well as the rate of no allergic patients who were prescribed one of these antibiotics; and pondering whether the allergic test is hence cost-effective. Methods This is a retrospective study developed from 2019 to 2021 focusing on patients suspected of β-lactams allergy (n=688). By means of an allergy test, it was cleared out if they were actually allergic. Later, we checked if the patient was still labelled as allergic in their medical record. Tracking through the digital health services card, we followed up if the antibiotic was ever prescribed again, and if the drug was then dispensed to the patient. Results 11.3% of the patients showed hypersensitivity to β-lactams. Nonetheless, 33.1% of the patients were still considered allergic to these antibiotics in their medical record even though not being such. 32% of the patients – who had their allergy confirmed – had been labelled without the general practitioner's acknowledgment, and 32.8% had even been prescribed a β-lactam again. Conclusions Discarding any allergy to β-lactams is as important as registering the allergy on medical records after testing the patient. A remarkable quantity of non-allergic patients is still addressed as actual allergic, in spite not being such. Labelling patients as β-lactams allergic may have consequences, short-term and long-term, for the patient but also for the health service budget. (AU)

[Efficiency of the allergological study in the diagnosis of allergic reactions to beta-lactams]. / Eficiencia del estudio alergológico en el diagnóstico de reacciones a ß-lactámicos.

AIMS: Assessing the rate of ß-lactams-allergic patients who are still labelled as such in their medical records after being performed an allergic test; as well as the rate of no allergic patients who were prescribed one of these antibiotics; and pondering whether the allergic test is hence cost-effective. METHODS: This is a retrospective study developed from 2019 to 2021 focusing on patients suspected of ß-lactams allergy (n=688). By means of an allergy test, it was cleared out if they were actually allergic. Later, we checked if the patient was still labelled as allergic in their medical record. Tracking through the digital health services card, we followed up if the antibiotic was ever prescribed again, and if the drug was then dispensed to the patient. RESULTS: 11.3% of the patients showed hypersensitivity to ß-lactams. Nonetheless, 33.1% of the patients were still considered allergic to these antibiotics in their medical record even though not being such. 32% of the patients - who had their allergy confirmed - had been labelled without the general practitioner's acknowledgment, and 32.8% had even been prescribed a ß-lactam again. CONCLUSIONS: Discarding any allergy to ß-lactams is as important as registering the allergy on medical records after testing the patient. A remarkable quantity of non-allergic patients is still addressed as actual allergic, in spite not being such. Labelling patients as ß-lactams allergic may have consequences, short-term and long-term, for the patient but also for the health service budget.

Use of whole blood over plasma enhances the detection of dengue virus RNA: possible utility in dengue vaccine trials.

In the present study, the utility of viral RNA isolated from whole blood over plasma for detection of dengue virus (DENV) was investigated in 80 samples referred for serotyping by DENV serotype-specific one-step real-time RT-PCR. DENV RNA was detected in 71.25% of the whole blood samples compared to 46.25% in the corresponding plasma samples. In secondary infections, DENV RNA was detected in 83.3% of whole blood samples, while it was detected in 40.5% of plasma samples (P = 0.0001). Non-structural protein 1 (NS1) antigen was detected in only 54.8% of the secondary infections. The detection rate of DENV RNA in whole blood is higher than in plasma. We suggest that one-step real-time RT-PCR using RNA from whole blood combined with an NS1 ELISA should be the choice for dengue diagnosis in dengue vaccine trials.

Spatio-temporal distribution analysis of circulating genotypes of dengue virus type 1 in western and southern states of India by a one-step real-time RT-PCR assay.

Dengue virus type 1 (DENV-1) Asian and American/African (AM/AF) genotypes were reported to be co-circulating in southern and western states of India based on envelope (E) gene sequencing of few representative samples. The objective of the present study was to develop a one-step real-time RT-PCR to discriminate between Asian and AM/AF genotypes of DENV-1 and investigate the spatio-temporal distribution of the DENV-1 genotypes in southern and western states of India. A one-step real-time RT-PCR to discriminate the Asian and AM/AF genotypes of DENV-1 was developed and validated using 40 samples (17 Asian and 23 AM/AF), for which the envelope (E) gene sequence data was available. DENV-2, DENV-3 and DENV-4 isolates, one each and DENV negative samples (n = 17) were also tested by the assay. Additional 296 samples positive for DENV-1 from selected Southern and Western states of India were genotyped using the real-time RT-PCR assay. Among the samples used for validation, the genotyping results were concordant with sequencing results for 39 samples. In the one discordant sample which was positive for AM/AF by sequencing, the genotyping assay tested positive for both Asian and AM/AF genotype. DENV-2, DENV-3 and DENV-4 isolates were not reactive in the assay. None of the DENV negative samples were positive (sensitivity 100% and specificity 98.2%). A total of 336 samples (40 samples with sequence data and 296 samples without sequence data) were used for spatio-temporal distribution analysis. The results revealed that the Asian genotype was the predominant genotype in Tamil Nadu and Kerala, the southern states. The AM/AF genotype was the predominant genotype in Maharashtra, a western state of India. In Nashik district of Maharashtra, Asian genotype was observed in 32.6% of DENV-1 samples during 2017 while the same decreased to 7.3% during 2018. In Pune district, Asian genotype was observed in 40.0% of DENV-1 samples during 2018 only. To conclude, a one step real-time RT-PCR has been developed for discriminating Asian and AM/AF genotypes of DENV-1. This assay can act as a complement to sequencing but not a substitute and can be utilized in resource limited settings for molecular surveillance of DENV-1. DENV-1 Asian genotype was the dominant genotype in South India while, AM/AF genotype was dominant in Western India.

An exploratory study of the effect of regular aquatic exercise on the function of neutrophils from women with fibromyalgia: role of IL-8 and noradrenaline.

Fibromyalgia (FM) syndrome is associated with elevated systemic inflammatory and stress biomarkers, and an elevated innate cellular response mediated by monocytes and neutrophils. Exercise is accepted as a good non-pharmacological therapy for FM. We have previously found that regular aquatic exercise decreases the release of inflammatory cytokines by monocytes from FM patients. However, its effects on the functional capacity of neutrophils have not been studied. The aim of the present exploratory study was to evaluate, in 10 women diagnosed with FM, the effect of an aquatic exercise program (8months, 2sessions/week, 60min/session) on their neutrophils' function (phagocytic process), and on IL-8 and NA as potential inflammatory and stress mediators, respectively. A control group of 10 inactive FM patients was included in the study. After 4months of the exercise program, no significant changes were observed in neutrophil function (chemotaxis, phagocytosis, or fungicidal capacity) or in IL-8 and NA. However, at the end of the exercise program (8months), a neuro-immuno-endocrine adaptation was observed, manifested by a significant decrease to values below those in the basal state in neutrophil chemotaxis, IL-8, and NA. No significant seasonal changes in these parameters were observed during the same period in the group of non-exercised FM patients. After the 8months of the exercise program, the FM patients had lower concentrations of IL-8 and NA together with reduced chemotaxis of neutrophils compared with the values determined in the same month in the control group of non-exercised FM women. These results suggest that "anti-inflammatory" and "anti-stress" adaptations may be contributing to the symptomatic benefits that have been attributed to regular aquatic exercise in FM syndrome, as was corroborated in the present study by the scores on the Fibromyalgia Impact Questionnaire.

Intraoperative radiotherapy with electrons: fundamentals, results, and innovation.

RATIONALE AND OBJECTIVES: To analyse the programme activity and clinical innovation and/or technology developed over a period of 17 years with regard to the introduction and the use of intraoperative radiotherapy (IORT) as a therapeutic component in a medical-surgical multidisciplinary cancer hospital. MATERIAL AND METHODS: To standardise and record this procedure, the Radiation Oncology service has an institutional programme and protocols that must be completed by the different specialists involved. For 17 years, IORT procedures were recorded on a specific database that includes 23 variables with information recorded on institutional protocols. As part of the development and innovation activity, two technological tools were implemented (RADIANCE and MEDTING) in line with the standardisation of this modality in clinical practice. RESULTS: During the 17 years studied, 1,004 patients were treated through 1,036 IORT procedures. The state of the disease at the time of IORT was 77% primary and 23% recurrent. The origin and distribution of cancers were 62% gastrointestinal, 18% sarcomas, 5% pancreatic, 2% paediatric, 3% breast, 7% less common locations, and 2% others. The research and development projects have generated a patent on virtual planning (RADIANCE) and proof of concept to explore as a professional social network (MEDTING). During 2012, there were 69 IORT procedures. There was defined treatment volume (target or target region) in all of them, and 43 were conducted by the virtual planning RADIANCE system. Eighteen have been registered on the platform MEDTING as clinical cases. CONCLUSION: The IORT programme, developed in a university hospital with an academic tradition, and interdisciplinary surgical oncology, is a feasible care initiative, able to generate the necessary intense clinical activity for tending to the cancer patient. Moreover, it is a competitive source for research, development, and scientific innovation.

Effects of habitual exercise on the eHsp72-induced release of inflammatory cytokines by macrophages from obese Zucker rats.

Regular exercise is a good non-pharmacological treatment of metabolic syndrome in that it improves obesity, diabetes, and inflammation. The 72 kDa extracellular heat shock protein (eHsp72) is released during exercise, thus stimulating the inflammatory responses. The aim of the present work was to evaluate the effect of regular exercise on the eHsp72-induced release of IL-1ß, IL-6, and TNFα by macrophages from genetically obese Zucker rats (fa/fa) (ObZ), using lean Zucker (LZ) rats (Fa/fa) to provide reference values. ObZ presented a higher plasma concentration of eHsp72 than LZ, and exercise increased that concentration. In response to eHsp72, the macrophages from ObZ released less IL-1ß and TNFα, but more IL-6, than macrophages from LZ. While eHsp72 stimulated the release of IL-1ß, TNFα, and IL-6 in the macrophages from healthy LZ (with respect to the constitutive release), it inhibited the release of IL-1ß and IL-6 in macrophages from ObZ. The habitual exercise improved the release of inflammatory cytokines by macrophages from ObZ in response to eHsp72 (it increased IL-1ß and TNFα, and decreased IL-6), tending to values closer to those determined in healthy LZ. A deregulated macrophage inflammatory and stress response induced by eHsp72 underlies MS, and this is improved by habitual exercise.

Aquatic exercise improves the monocyte pro- and anti-inflammatory cytokine production balance in fibromyalgia patients.

Current hypotheses of the etiology of fibromyalgia (FM) include inflammatory disorders. We evaluated the effect of a pool-aquatic exercise program (8 months, two weekly 60-min sessions) on the inflammatory cytokine production by isolated monocytes, and on the serum concentration of C-reactive protein (CRP), in a group of female FM patients. Monocytes from FM patients released more IL-1ß, TNFα, IL-6, and IL-10 than those from an age-matched control group of healthy women (HW). This inflammatory disorder in FM women was also manifested by high circulating concentrations of CRP. Increased IL-6 with a concomitant decreased TNFα spontaneous release was found after 4 months (midway through) of the exercise program. At the end of the program (8 months), monocytes from FM patients showed diminished spontaneous production of pro-/anti-inflammatory cytokines, with a similar spontaneous release of IL-1ß and IL-6 to that of HW, but a lower production of TNFα and higher of IL-10. Lipopolysaccharide-induced production of IL-1ß, TNFα, IL-6, and IL-10 also decreased at the end of the exercise program, although IL-10 remained higher than HW. The anti-inflammatory effect of the exercise program was also corroborated by a decrease in the circulating CRP concentration. Exercise also improved the health-related quality of life of FM patients.

Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances.

Fibromyalgia (FM) is characterised by chronic widespread pain and allodynia (pain from stimuli which are not normally painful with pain that may occur other than in the area stimulated) of more than 3 months duration. The current hypothesis of the aetiology of FM includes inflammatory and neuroendocrine disorders. The biophysiology of this syndrome, however; remains still widely elusive, and there are no formally approved therapies. Non-pharmacological interventions in FM patients include habitual exercise programs which improve physical function and quality of life of patients and may even reduce pain. However the mechanisms through which exercise benefits FM symptoms needs to be elucidated. In this article we firstly review the main topics and characteristics of the FM syndrome, while focusing our attention on the inflammatory hypothesis of FM, as well as on the beneficial effects of habitual exercise as a co-therapy for FM patients. In this context, the latest developments in research on anti-inflammatory effects of exercise are also reviewed and discussed. To find out what is known about the connection between benefits of exercise for FM and anti-inflammatory effects of exercise, we carried out a PubMed search using the term "fibromyalgia" and "exercise" together with "inflammation", and no more than ten published articles were found (six of them reviews), which are also discussed. In the second part of the article we present a pilot investigation on a group of 14 female FM patients with a diagnosis of FM by a rheumatologist. They took part in a pool-aquatic program in warm water over a period of fourth months (three weekly 60-min sessions). Circulating inflammatory (IL-1beta, IL-2, IFNgamma, TNFalpha, IL-8, IL-6, IL-4, IL-10 and CRP) and neuroendocrine (NA and cortisol) markers were determined. FM patients showed higher circulating levels of IL-8, IFNgamma and CRP as well as cortisol and NA than age-matched healthy control women. After the exercise program, a significant decrease in IL-8, IFNgamma, and CRP were found, in parallel with a decrease in circulating concentrations of cortisol and increased levels of NA. The results confirm an elevated "inflammatory status" in the FM syndrome and strengthen the hypothesis that the benefits of exercise in FM patients are mediated, at least in part, by its anti-inflammatory effects. A better regulation of the cytokine-HPA axis feedback may be also involved.

Quality assurance in radiation therapy: systematic evaluation of errors during the treatment execution.

A method to control the quality of the radiotherapy treatment during its execution has been developed. The method is based on a wide use of verification films in the practical routine of a centre together with a statistical analysis of the data obtained from them. The stepwise multiple regression analysis is applied in order to assess the influence, on the quality of the treatment, of a set of chosen factors with a certain clinical or technical significance. A test of the method is presented and the results are discussed.