Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Clinical, Radiological, and Outcome Characteristics of Acute Pulmonary Embolism: A 5-year Experience from an Academic Tertiary Center.

BACKGROUND: Acute pulmonary embolism (PE) is a common and potentially life-threatening condition. This comprehensive study from a Gulf Cooperation Council (GCC) country aimed to evaluate the clinical, radiological, and outcome characteristics associated with acute PE. METHODS: This retrospective observational study analyzed data of patients with confirmed acute PE who were admitted to the largest academic tertiary center in the State of Qatar from January 1, 2014, to December 31, 2018. Data on the clinical presentation, radiologic, and echocardiographic findings, as well as outcomes were collected. RESULTS: A total of 436 patients were diagnosed with acute PE during the study period (male, 53%). Approximately 56% of the patients were < 50 years old at presentation, with a median age of 47 years. In approximately 69% of cases, the PE occurred outside the hospital. The main associated comorbidities were obesity (34.6%), hypertension (29.4%), and diabetes (25%). Immobilization (25.9%) and recent surgery (20.6%) were the most common risk factors. The most frequent presenting symptom was dyspnea (39.5%), and the most frequent signs were tachycardia (49.8%) and tachypnea (45%). Cardiac arrest was the initial presentation in 2.2% of cases. Chest X-ray findings were normal in 41%. On computed tomography pulmonary angiography (CTPA), 41.3% of the patients had segmental PE, 37.1% had central PE, and 64.1% had bilateral PE. The main electrocardiographic (ECG) abnormality was sinus tachycardia (98%). In patients who underwent echocardiography, right ventricular (RV) enlargement was the main echocardiographic finding (36.4%). Low-, intermediate-, and high-risk PE constituted 49.8%, 31.4%, and 18.8% of the cases, respectively. Thrombolysis was prescribed in 8.3% of the total and 24.4% of the high-risk PE cases. Complications of PE and its treatment (from admission up to 6 months post-discharge) included minor bleeding (14%), major bleeding (5%), PE recurrence (4.8%), and chronic thromboembolic pulmonary hypertension (CTEPH) (5%). A total of 15 (3.4%) patients died from PE. CONCLUSIONS: Acute PE can manifest with complex and variable clinical and radiological syndromes. Striking findings in this study are the younger age of acute PE occurrence and the low PE-related mortality rate.

Saddle versus non-saddle pulmonary embolism: differences in the clinical, echocardiographic, and outcome characteristics.

The central location, the size, and instability of saddle pulmonary embolism (PE) have raised considerable concerns regarding its hemodynamic consequences and the optimal management approach. Sparse and conflicting reports have addressed these concerns in the past. We aimed to evaluate the clinical presentation, hemodynamic and echocardiographic effects, as well as the outcomes of saddle PE, and compare the results with those of non-saddle type. This was a retrospective study of 432 adult patients with saddle and non-saddle PE. Overall, 432 patients were diagnosed with PE by computed tomography pulmonary angiography (CTPA). Seventy-three (16.9%) had saddle PE, and 359 had non-saddle PE. Compared to those with non-saddle PE, patients with saddle PE presented more frequently with tachycardia (68.5% vs. 46.2%, P= .001), and tachypnea (58.9% vs. 42.1%, P= .009) on admission, required more frequent intensive care unit (ICU) admissions (45.8% vs. 26.6%, P= .001) and thrombolysis/thrombectomy use (19.1% vs. 6.7%, P= .001), and were at more risk of developing decompensation and cardiac arrest after their initial admission (15.3% vs. 5.9%, P= .006). On echocardiography, right ventricular (RV) enlargement (60% vs. 31.1%, P= .000), RV dysfunction (45.8% vs. 22%, P= .000), and RV systolic pressure (RVSP) of greater than 40 mmHg (61.5% vs. 39.2%, P= .003) were significantly more observed with saddle PE. The two groups did not differ concerning the rates of hypotension (17.8% vs. 18.7%, P= .864) and hypoxemia (41.1% vs. 34.3%, P= .336) on admission and mortality rates. A logistic regression model indicated that the use of oral contraceptive pills (OCP), RVSP > 40 mmHg, and development of hypotension and decompensation following admission were associated with an increased likelihood of having saddle embolus. Saddle PE accounts for a higher proportion among all PE cases than previously reported. Patients with saddle PE tend to present more frequently with adverse hemodynamic and echocardiographic changes and decompensate after their initial presentation. OCP use, development of hypotension, and decompensation following admission and RVSP > 40 mmHg are significant predictors of saddle PE. These characteristics should not be overlooked when managing patients with saddle PE.

Recommendations by the Spanish Society of Rheumatology on the management of patients with fibromyalgia. Part II.

OBJECTIVE: To prevent the deterioration of patients with fibromyalgia due to potentially avoidable harmful actions in clinical practice. METHODS: A multidisciplinary panel of experts identified key areas, analysed the scientific evidence and formulated recommendations based on this evidence and qualitative techniques of "formal assessment" or "reasoned judgement". RESULTS: Thirty-nine recommendations were made on diagnosis, ineffective and unsafe treatments, patient education and practitioner training. This part II shows the 12 recommendations, referring to the latter two areas. CONCLUSIONS: Good knowledge of fibromyalgia on the part of patients improves their coping and acceptance of the disease and reduces the severity of some clinical manifestations. Healthcare professionals treating patients with fibromyalgia should be well trained in this disease to improve treatment outcomes and patient relationships.

Recommendations by the Spanish Society of Rheumatology on Fibromyalgia. Part 1: Diagnosis and treatment.

OBJECTIVE: To prevent the impairment of fibromyalgia patients due to harmful actions in daily clinical practice that are potentially avoidable. METHODS: A multidisciplinary team identified the main areas of interest and carried out an analysis of scientific evidence and established recommendations based on the evidence and "formal evaluation" or "reasoned judgment" qualitative analysis techniques. RESULTS: A total of 39 recommendations address diagnosis, unsafe or ineffective treatment interventions and patient and healthcare workers' education. This part I shows the first 27 recommendations on the first 2 areas. CONCLUSIONS: Establishing a diagnosis improves the patient's coping with the disease and reduces healthcare costs. NSAIDs, strong opioids and benzodiazepines should be avoided due to side effects. There is no good evidence to justify the association of several drugs. There is also no good evidence to recommend any complementary medicine. Surgeries show a greater number of complications and a lower degree of patient satisfaction and therefore should be avoided if the surgical indication is not clearly established.

Recommendations by the Spanish Society of Rheumatology on the Management of Patients with Fibromyalgia. Part II. / Recomendaciones SER sobre el manejo de los pacientes con fibromialgia. Parte II.

OBJECTIVE: To prevent the deterioration of patients with fibromyalgia due to potentially avoidable harmful actions in clinical practice. METHODS: A multidisciplinary panel of experts identified key areas, analysed the scientific evidence and formulated recommendations based on this evidence and qualitative techniques of «formal assessment¼ or «reasoned judgement¼. RESULTS: Thirty-nine recommendations were made on diagnosis, ineffective and unsafe treatments, patient education and practitioner training. This partII shows the 12 recommendations, referring to the latter two areas. CONCLUSIONS: Good knowledge of fibromyalgia on the part of patients improves their coping and acceptance of the disease and reduces the severity of some clinical manifestations. Healthcare professionals treating patients with fibromyalgia should be well trained in this disease to improve treatment outcomes and patient relationships.

Recommendations by the Spanish Society of Rheumatology on Fibromyalgia. Part 1: Diagnosis and Treatment. / Recomendaciones SER sobre el manejo de los pacientes con fibromialgia. Parte I: diagnóstico y tratamiento.

OBJECTIVE: To prevent the impairment of fibromyalgia patients due to harmful actions in daily clinical practice that are potentially avoidable. METHODS: A multidisciplinary team identified the main areas of interest and carried out an analysis of scientific evidence and established recommendations based on the evidence and "formal evaluation" or "reasoned judgment" qualitative analysis techniques. RESULTS: A total of 39 recommendations address diagnosis, unsafe or ineffective treatment interventions and patient and healthcare workers' education. This part I shows the first 27 recommendations on the first 2 areas. CONCLUSIONS: Establishing a diagnosis improves the patient's coping with the disease and reduces healthcare costs. NSAIDs, strong opioids and benzodiazepines should be avoided due to side effects. There is no good evidence to justify the association of several drugs. There is also no good evidence to recommend any complementary medicine. Surgeries show a greater number of complications and a lower degree of patient satisfaction and therefore should be avoided if the surgical indication is not clearly established.

Effect of continuous feeding of CO2 and pH in cell concentration and product titers in hIFNγ producing HEK293 cells: Induced metabolic shift for concomitant consumption of glucose and lactate.

Although pH control at physiological levels is generally considered as the optimal culture condition, in some cases other strategies should be taken into account for their beneficial effects on process performance. pH and CO2 levels are chemical variables that have a major impact in cell growth and product titers in cell culture since their effect on key metabolic routes. HEK293 cells expressing recombinant hIFNγ showed different metabolic behavior when cultured in shake flask compared to pH-controlled bioreactors, in which a decrease in cell density and product titer were observed. This yield loss observed in bioreactor cultures could be reverted by adding 1% CO2 to air inlet flow in a non-controlled pH bioprocess. With this strategy, a significant outcome of 4-fold increase in terms of maximum cell density and 2-fold increase in volumetric concentration of recombinant protein (hIFNγ) when compared to the pH-controlled culture in bioreactor (standard culture conditions) has been obtained. Results evidenced the importance of pH and CO2 concentration in this case, in order to reproduce the behavior observed in optimization experiments performed in shake flasks. Thus, it was demonstrated that not always constant controlled variable setpoint (like pH or CO2 addition) becomes the best bioprocess performance strategy.

Variable Inter-assay Estimation of Sperm DNA Fragmentation In Stallions Classified as Good and Bad Semen Freezers.

BACKGROUND: Semen cryopreservation causes DNA damage, thus requiring continuous monitoring. OBJECTIVE: To compare two assays for sperm DNA fragmentation (SDF) from stallions with contrasting semen freezability. MATERIALS AND METHODS: Thirteen stallions were classified as good semen freezers (GSF) or bad semen freezers (BSF). Ejaculates were cryopreserved with three diluents. Semen was subject to SDF evaluation using the sperm chromatin structure assay (SCSA) and Halomax after thawing (0 h) and after a 4 h thermoresistance test. RESULTS: On semen of BSF, analysis by SCSA was similar between evaluations, but Halomax showed increased SDF at 4 h. The GSF group was similar between time points in both assays. Diluents did not affect SDF, irrespective of the assay. Halomax showed differences for BSF between time points, differently from SCSA. Linear regression did not show any correlation between assays. CONCLUSION: The use of Halomax should be encouraged for sperm DNA fragmentation analysis in horse frozen-thawed semen, particularly under field conditions.

Is the performance of MRI in preoperative staging of breast cancer independent of clinical and histological factors? A subgroup analysis.

OBJECTIVE: To determine whether preoperative breast MRI is more useful in patients according to their breast density, age, menopausal status, and biopsy findings of carcinoma in situ. MATERIAL AND METHODS: We retrospectively studied 264 patients treated for breast cancer who had undergone mammography, ultrasonography, and MRI. We compared the size of the tumor on the three techniques and the sensitivity of the techniques for detecting additional lesions both in the overall group and in subgroups of patients classified according to their breast density, age, menopausal status, and histological findings of intraductal carcinoma. The definitive histological diagnosis was used as the gold standard. RESULTS: MRI was the technique that was most concordant with the histological findings for the size of the lesion, and it was also the technique that detected the most additional lesions. With MRI, we observed no differences in lesion size between the overall group and the subgroups in which MRI provided added value. Likewise, we observed no differences in the number of additional lesions detected in the overall group except for multicentric lesions, which was larger in older patients (P=.02). In the subgroup of patients in which MRI provided added value, the sensitivity for bilateral lesions was higher in patients with fatty breasts (P=.04). Multifocal lesions were detected significantly better in premenopausal patients (P=.03). CONCLUSIONS: MRI is better than mammography and better than ultrasonography for establishing the size of the tumor and for detecting additional lesions. Our results did not identify any subgroups in which the technique was more useful.

[The computerized repeat prescription. The follow-up of drug consumption and of authorized medication cards over the first 3 years]. / Prescripción repetida informatizada. Seguimiento del consumo de fármacos y de las tarjetas de medicación autorizada los 3 primeros años.

OBJECTIVE: To find the characteristics of the quantitative data and their evolution from June 1993 to June 1996 concerning our system of computerised repeat prescriptions (CRP). DESIGN: A population-based, longitudinal and observational study. SETTING: Raval Nord Primary Care District, Barcelona. PARTICIPANTS: All the authorized medication cards (AMC) from the first, second and third years, collected in dBASE-IV. MEASUREMENTS AND MAIN RESULTS: Overall number of AMC, for pensioners and workers, total number of medicines, mean medicines per AMC, mean attendance of patients by days and mean counterfoils per doctor per month. Sex and age in 1996. The overall number of AMC fell from 3,432 to 3,129. Users attended the CRP service every 68.44 days, which did not change. Overall medicines fell from 12,392 to 11,108. Mean medicines per AMC fell from 3.61 to 3.55. Mean counterfoils per doctor per month fell for pensioners from 18.20 to 14.45, and for workers from 2.00 to 1.63. CONCLUSIONS: There was a steady fall in all the indicators under study. The profile of the user with an AMC is a woman, pensioner, 65 or over, using the CRP service every two months, with 3.5 authorized medicines per year and receiving steadily less prescriptions.