Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency and performance. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% sodium chloride (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to normal saline, to see if the evidence establishes whether one is better than the other. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus normal saline. We excluded studies on infants and children from this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were occlusion of CVCs and duration of catheter patency. Our secondary outcomes were CVC-related bloodstream infections and CVC-related colonisation, mortality, haemorrhage, heparin-induced thrombocytopaenia, CVC-related thrombosis, number of additional CVC insertions, abnormality of coagulation profile and allergic reactions to heparin. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified one new RCT with 30 participants for this update. We included a total of 12 RCTs with 2422 participants. Data for meta-analysis were available from all RCTs. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Five studies included ICU (intensive care unit) patients, two studies included oncology patients, and the remaining studies included miscellaneous patients (chronic kidney disease, haemodialysis, home care patients, etc.). Primary outcomes Overall, combined results may show fewer occlusions with heparin compared to normal saline but this is uncertain (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; 10 studies; 1672 participants; low-certainty evidence). We pooled studies that used participant or catheter as the unit of analysis. We carried out subgroup analysis by unit of analysis. No clear differences were detected after testing for subgroup differences (P = 0.23). We found no clear evidence of a difference in the duration of catheter patency with heparin compared to normal saline (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; 6 studies; 1788 participants; low-certainty evidence). Secondary outcomes We found no clear evidence of a difference in the following outcomes: CVC-related bloodstream infections (RR 0.66, 95% CI 0.08 to 5.80; 3 studies; 1127 participants; very low-certainty evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; 3 studies; 1100 participants; very low-certainty evidence); haemorrhage (RR 1.54, 95% CI 0.41 to 5.74; 3 studies; 1197 participants; very low-certainty evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; 3 studies; 443 participants; very low-certainty evidence). The main reasons for downgrading the certainty of evidence for the primary and secondary outcomes were unclear allocation concealment, suspicion of publication bias, imprecision and inconsistency. AUTHORS' CONCLUSIONS: Given the low-certainty evidence, we are uncertain whether intermittent locking with heparin results in fewer central venous catheter occlusions than intermittent locking with normal saline in adults. Low-certainty evidence suggests that heparin may have little or no effect on catheter patency duration. Although we found no evidence of differences in safety (CVC-related bloodstream infections, mortality, or haemorrhage), the combined studies were not powered to detect rare adverse events such as heparin-induced thrombocytopaenia. Further research conducted over longer periods would reduce the current uncertainties.

Analysis of chemical contamination by hazardous drugs with BD HD Check® system in a tertiary hospital.

The presence of contamination in the healthcare work environment by one of the types of hazardous drugs, cytostatics, has been found in multiple international studies. Recent studies and guidelines recommend surface monitoring for risk assessment of healthcare professionals' exposure. The availability of detection techniques is critical to successfully carry out this type of monitoring. The use of new semi-quantitative techniques allows quicker results. The main objective of this study was to determine the existence of hazardous drugs on the working surfaces in different locations of a tertiary hospital using the BD HD Check® semi-quantitative device. The presence of methotrexate, doxorubicin and cyclophosphamide was analysed at 80, 89 and 82 locations in 10, 13 and 11 clinical units, respectively. A total of 251 samples were analysed. The monitoring results were positive for 13.1% of the analysed samples, with 36.3% of the methotrexate samples, 0% of the doxorubicin samples and 4.9% of the cyclophosphamide samples. Mapping the presence of HD in our hospital has allowed us to evaluate the effectiveness of controls established in the hospital to minimise the exposure of healthcare professionals to hazardous drugs. The speed in obtaining results has enabled immediate corrective actions in cases where contaminated surfaces were detected.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain.

AIM: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use. DESIGN: Systematic review. DATABASES: Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021. SELECTION CRITERIA: Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain). DATA TREATMENT: The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence. RESULTS: Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability. CONCLUSIONS: This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Clinical characteristics of admission for mental illness in a Regional Psychiatric Hospitalization Unit. Descriptive study 2008-2018 / Características clínicas del ingreso por enfermedad mental en una Unidad de Hospitalización Psiquiátrica Comarcal. Estudio descriptivo 2008-2018.

Objective: To describe the admissions of patients diagnosed with severe mental illness (SMI) and anxiety disorder in a regional hospital; to explore factors related to the patient's referrer upon admission and prolonged stay. Materials and methods: Cross-sectional study of episodes of admission to the regional Psychiatric Hospitalization Unit over a period of 11 years with ICD-10 diagnostic codesF20-29, F30-39, F60-69 and F40-48. The data was extracted through the Admissions Unit and the information from the electronic medical record. For the statistical treatment, descriptive or inferential tests were used with a confidence level of 95%. Results: 961 patients were included (2,324 total discharges), aged 40.8±14.0 years. The most frequent reasons for admission were: positive symptoms (agitation, delusions and hallucinations), followed by suicidal ideation and attempt. The main remitting agent of the patients was the family itself. Approximately 1/5 of the cases were referred by the health system itself, and » of those admitted had self-excluded themselves from specialized supervision for more than a year. Conclusions: The problems that caused the admission and its origin, as well as its lack of follow-up, can be considered as a clear opportunity for improvement in the follow-up of patients with severe mental illness. An orientation towards proactivity, acting before the decompensation, would contribute to improving the care and quality of life of patients with severe mental illness and their environment.

Objetivo: Describir los ingresos de pacientes diagnosticados de enfermedad mental grave y trastorno de ansiedad en un hospital comarcal; explorar los factores relacionados con la derivación del paciente al ingreso y con estancia prolongada. Materiales y métodos: Estudio de corte transversal de los episodios de ingreso en la Unidad de Hospitalización Psiquiátrica comarcal en un periodo de 11 años con los códigos diagnósticos CIE-10 F20-29, F30-39, F60-69 y F40-48. Se extrajeron los datos a través de la Unidad de Admisión y la información de la historia clínica electrónica. Para el tratamiento estadístico se usaron pruebas descriptivas o inferenciales con nivel de confianza del 95%. Resultados: Se incluyeron 961 pacientes (2.324 altas totales), con edad de 40,8±14,0 años. Los motivos más frecuentes de ingreso fueron: síntomas positivos (agitación, delirios y alucinaciones), seguidos de ideación e intento de suicidio. El principal agente remisor de los pacientes fue la propia familia. Aproximadamente 1/5 de casos fue derivado por el propio sistema sanitario, y » de los ingresados se había autoexcluido de la supervisión especializada durante más de un año. Conclusiones: Los problemas causantes del ingreso y su procedencia, así como su falta de seguimiento, pueden considerarse como una oportunidad clara de mejora en el seguimiento del paciente con enfermedad mental grave. Una orientación hacia la proactividad, actuando antes de la descompensación, contribuiría a mejorar la asistencia y calidad de vida de los pacientes con enfermedad mental grave y su entorno.

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% NaCl (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9% NaCl to see if the evidence establishes whether one is better than the other. This work is an update of a review first published in 2014. OBJECTIVES: To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline (NS) in adults to prevent occlusion. SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 11 June 2018) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5). Searches were also carried out in MEDLINE, Embase, CINAHL, and clinical trials databases (11 June 2018). SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus NS. We applied no restriction on language. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality, and extracted data. We contacted trial authors to retrieve additional information, when necessary. We carried out statistical analysis using Review Manager 5 and assessed the overall quality of the evidence supporting assessed outcomes using GRADE. We carried out prespecified subgroup analysis. MAIN RESULTS: We identified five new studies for this update (six prior studies were included in the original review), bringing the number of eligible studies to 11, with a total of 2392 participants. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access).Combined results from these studies showed fewer occlusions with heparin than with NS (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%) and provided very low-quality evidence.We carried out subgroup analysis by unit of analysis (testing for subgroup differences (P = 0.23; I² = 30.3%). When the unit of analysis was the participant, results show no clear differences in all occlusions between heparin and NS (RR 0.79, 95% CI 0.58 to 1.08; P = 0.15; 1672 participants; seven studies). Subgroup analysis using the catheter as the unit of analysis shows fewer occlusions with heparin use (RR 0.53, 95% CI 0.29 to 0.95; P = 0.03; 1025 catheters; three studies). When the unit of analysis was line access, results show no clear differences in occlusions between heparin and NS (RR 1.08, 95% CI 0.84 to 1.40; 770 line accesses; one study).We found no clear differences in the duration of catheter patency (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; P = 0.11; 1036 participants; 752 catheters; six studies; low-quality evidence).We found no clear evidence of a difference in the following: CVC-related sepsis (RR 0.74, 95% CI 0.03 to 19.54; P = 0.86; 1097 participants; two studies; low-quality evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; P = 0.33; 1100 participants; three studies; low-quality evidence); haemorrhage at any site (RR 1.32, 95% CI 0.57 to 3.07; P = 0.52; 1245 participants; four studies; moderate-quality evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; P = 0.31; 443 participants; three studies; low-quality evidence).The main reasons for downgrading the quality of evidence were unclear allocation concealment, imprecision, and suspicion of publication bias. AUTHORS' CONCLUSIONS: Given the very low quality of the evidence, we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS. Low-quality evidence suggests that heparin may have little or no effect on catheter patency. Although we found no evidence of differences in safety (sepsis, mortality, or haemorrhage), the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia.

Pre and post intervention study of antiblastic drugs contamination surface levels at a Pharmacy Department Compounding Area using a closed system drug transfer device and a decontamination process.

Assuring healthcare workers security on Hazardous Drugs (HD) compounding is critical in healthcare settings. Our study aims to demonstrate that the use of a Close System drug Transfer Device (CSTD) PhaSeal™ added to a decontamination process reduces antiblastic surface contamination levels in the Compounding Area (CA) of our Pharmacy Department (PD). We selected cyclophosphamide, 5-fluorouracil and iphosphamide to be evaluated. Testing was carried out with a wipe kit and quantified by an independent laboratory. We defined four sampling times: baseline; just after a decontamination procedure, which was repeated weekly during the study; four months after introduction of CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil compounding; and after eight months using CSTD PhaSeal™ for cyclophosphamide and 5-fluorouracil and one month for iphosphamide compounding. There was a decrease at the number of positive samples at the beginning/end of the study for all the drugs tested: 28/15 for cyclophosphide, 29/23 for iphosphamide and 7/1 for 5-fluorouracile. Comparing to the baseline, median cyclophosphamide levels significantly decreased (p-value <0.001) at 4 and 8 months sampling time (baseline: 1.01 ng/cm2 to 0.06 ng/cm2 and 0.01 ng/cm2), and median iphosphamide levels significantly decreased (p < 0.001) at 8 months sampling time (baseline: 3.02 ng/cm2 to 0.06 ng/cm2). 5-Fluorouracil did not show significant differences between the sampling times (baseline: 0.09 ng/cm2 to 0.09 ng/cm2). We saw a significant increase at iphosphamide levels at 4 months sampling point, contrary to cyclophosphamide, which levels had decreased. The use of CSTD PhaSeal™ for iphosphamide compounding the last month was implemented for ethical reasons after this intermediate results review. Our study suggests that the use of CSTD PhaSeal™, adding to decontaminating procedures, significantly reduces antiblastic drug surface levels at the CA of our PD.

Early experience with compassionate use of 2 hydroxypropyl-beta-cyclodextrin for Niemann-Pick type C disease: review of initial published cases.

Niemann-Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-ß-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-ß-CD was 14 years (range 2-49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-ß-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-ß-CD in NP-C.

Heparin versus 0.9% sodium chloride intermittent flushing for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Heparin intermittent flushing is a standard practice in the maintenance of patency in central venous catheters. However, we could find no systematic review examining its effectiveness and safety. OBJECTIVES: To assess the effectiveness of intermittent flushing with heparin versus 0.9% sodium chloride (normal saline) solution in adults with central venous catheters in terms of prevention of occlusion and overall benefits versus harms. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched December 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11). Searches were also carried out in MEDLINE, EMBASE, CINAHL and clinical trials databases (December 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) in adults 18 years of age and older with a central venous catheter (CVC) in which intermittent flushing with heparin (any dose with or without other drugs) was compared with 0.9% normal saline were included. No restriction on language was applied. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data. Trial authors were contacted to retrieve additional information, when necessary. MAIN RESULTS: Six eligible studies with a total of 1433 participants were included. The heparin concentrations used in these studies were very different (10-5000 IU/mL), and follow-up varied from 20 days to 180 days. The overall risk of bias in the studies was low. The quality of the evidence ranged from very low to moderate for the main outcomes (occlusion of CVC, duration of catheter patency, CVC-related sepsis, mortality and haemorrhage at any site).Combined findings from three trials in which the unit of analysis was the catheter suggest that heparin was associated with reduced CVC occlusion rates (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.29 to 0.94). However, no clear evidence of a similar effect was found when the results of two studies in which the unit of analysis was the participant were combined (RR 0.21, 95% CI 0.03 to 1.70), nor when findings were derived from one study, which considered total line accesses (RR 1.08, 95% CI 0.84 to 1.40). Furthermore, results for other estimated effects were found to be imprecise and compatible with benefit and harm: catheter duration in days (mean difference (MD) 0.41, 95% CI -1.29 to 2.12), CVC-related thrombosis (RR 1.22, 95% CI 0.74 to 1.99), CVC-related sepsis (RR 1.02, 95% CI 0.34 to 3.03), mortality (RR 0.77, 95% CI 0.45 to 1.32) and haemorrhage at any site (RR 1.37, 95% CI 0.49 to 3.85). AUTHORS' CONCLUSIONS: We found no conclusive evidence of important differences when heparin intermittent flushing was compared with 0.9% normal saline flushing for central venous catheter maintenance in terms of efficacy or safety. As heparin is more expensive than normal saline, our findings challenge its continued use in CVC flushing outside the context of clinical trials.

Real world effectiveness and safety of nivolumab in patients with relapsed or refractory classical hodgkin lymphoma. / Efectividad y seguridad en vida real de nivolumab en pacientes con linfoma de hodgkin clásico en recaída o refractario.

OBJECTIVE: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy. METHOD: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival and overall survival. Safety was measured as percentage of patients with adverse effects and severity. RESULTS: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2.0-4.5), including autologous hematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3.0-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%) and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95%CI: 0-49.1), median overall survival was not reached. At the study cutoff date, five patients had died (38.5%), four were in complete remission without active treatment (30.8%) and four were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, two suffered treatment delays (thrombocytopenia and hypertransaminemia) and one changed the regimen to monthly (pulmonary toxicity). CONCLUSIONS: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed in the study sample favorable effectiveness data, expressed as objective response rate of 46.2% and clinical benefit of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature.

Onasemnogene Abeparvovec Administration via Peripherally Inserted Central Catheter: A Case Report.

Onasemnogene abeparvovec (OA) is the approved intravenous gene therapy for the treatment of spinal muscular atrophy (SMA). A functional copy of the human SMN1 gene was inserted into the target motor neuron cells via a viral vector, AAV9. In clinical trials, OA was infused through a peripheral venous catheter, and no data are available on central catheter use. Recently, we had a case where OA was administered directly into the right atrium via a peripherally inserted central catheter (PICC) instead of a peripheral line, as recommended. The patient was a female child aged 4 months, diagnosed as SMA type I. For practical reasons, a dose of OA according to the weight of the patient (1.1 × 1014 vectorial genomes/kg) was administered via PICC in 1 h, as the product information recommends. The drug was well tolerated, with no hypersensitivity reactions or initial elevation of transaminases or other adverse effects. To our knowledge, this is the first case reported where OA was administered via a central line. This type of administration is not contraindicated, but it is not specifically contemplated or recommended. It is unknown whether central line administration could have any implications for transduction efficiency and immunogenicity. Future studies should clarify these aspects, as each gene therapy has a specific optimal dose recorded that depends on the site and route of administration of the drug, the AAV variant and the transgene.

Megestrol acetate for treatment of anorexia-cachexia syndrome.

BACKGROUND: This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH METHODS: We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. SELECTION CRITERIA: Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. DATA COLLECTION AND ANALYSIS: Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. MAIN RESULTS: We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied. AUTHORS' CONCLUSIONS: This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Selective ophthalmic intra-arterial melphalan therapy for advanced retinoblastoma: implementation and outcomes of a new chemotherapy protocol.

Retinoblastoma is a relatively uncommon childhood tumor. If untreated, RB grows to fill the eye and destroys the ocular globe's internal architecture. Metastatic spread usually begins after the first 6 months, and death occurs within a matter of years. When treated, overall survival rounds 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localized treatment. In our hospital, pediatric oncologists asked the Pharmacy Department for assessment in order to implement a new chemotherapy protocol for the treatment of advanced intraocular elegible retinoblastoma cases using melphalan administered directly through the ophthalmic artery. In this paper, we describe the protocol implementation carried out by our collaborative interdisciplinary team as well as the clinical outcomes of five cases treated with ophthalmic intra-arterial melphalan therapy. Oncology pharmacists can contribute with their knowledge to the implementation process of new collaborative practice protocols recommending doses, predicting possible adverse effects and assessing about drug stability and elaboration, packaging and administration methods.

Patient benefit as a goal of humanization.

Patient empowerment is one of the main pillars of humanisation. Therefore, consideration of patients' preferences and expectations should be  taken into account during the practice of any healthcare professional.  Improving overall survival and quality of life are the main wishes of patients.  Indeed, the recent emergence of Patient Reported Outcomes has become an important focus for healthcare providers. The hospital pharmacist  specialised in drug evaluation is a professional who evaluates the efficacy,  safety, appropriateness and efficiency of treatments prescribed by physicians, and decision-making must be based on both technical factors and  the four principles of bioethics. The correct application of evidence-based  clinical practice allows to provide patients with increases in survival and/or quality of life, adapting the convenience and costs to the current  situation. With this in mind, it could be said that the evaluation of medicines  involves a strong commitment to humanisation. On the other hand,  rganisations that promote the rigorous evaluation and selection of medicines  stand as allies of patients, as they have a direct impact on them and an  indirect impact on society. Regulatory agencies in charge of approving and  financing medicines in healthcare systems play a key role in the process of humanising clinical decision-making and empowering patients. If  these agencies approve the use of new medicines based on data that do not measure quality of life or survival of patients when there are already other therapeutic alternatives for these pathologies, they are indirectly failing  to meet patients' expectations and are infringing bioethical principles. This can  have a considerable influence on the benefit-risk ratio of drugs, and  patients  may be treated with regimens that do not provide benefit, or may even harm  them. Therefore, where should the process of humanisation be oriented? It  seems reasonable that the benefit of the patient should be the fundamental  objective of the process of humanisation of healthcare, evidently.

El empoderamiento del paciente supone uno de los principales pilares de la  humanización. Por ello, la consideración de las preferencias y expectativas de  los pacientes debería ser tenida en cuenta durante el ejercicio de cualquiera de  los profesionales de la salud. Mejorar la supervivencia global y la calidad de  vida son los deseos principales de los pacientes. De hecho, la reciente  aparición de los llamados Patient Reported Outcomes ha supuesto un  importante foco para los agentes involucrados en la asistencia sanitaria. El  farmacéutico hospitalario especializado en la evaluación de medicamentos es  un profesional que evalúa la eficacia, seguridad, adecuación y eficiencia de los  tratamientos prescritos por facultativos, y debe basar la toma de decisiones  tanto en factores técnicos como en los cuatro principios bioéticos. La correcta  aplicación de la práctica clínica basada en la evidencia permite proveer a los  pacientes de incrementos de supervivencia y/o calidad de vida, adecuando la  conveniencia y costes a la situación actual. Teniendo en cuenta esto, podría  decirse que la evaluación de medicamentos supone un fuerte compromiso con  la humanización. Por otra parte, las organizaciones que promueven la  evaluación y selección de medicamentos rigurosamente se erigen como aliados  de los pacientes, ya que repercuten de forma directa en éstos y de  forma indirecta en la sociedad. Las agencias reguladoras encargadas de la  aprobación y financiación de medicamentos en los sistemas sanitarios  protagonizan un papel fundamental en el proceso de humanización de la toma  de decisiones clínicas y empoderamiento de pacientes, ya que si aprueban el  uso de nuevos medicamentos según datos que no miden la calidad de vida o  supervivencia de los pacientes cuando ya existen otras alternativas  terapéuticas para estas patologías, indirectamente no estarán dando respuesta a las expectativas de los pacientes y conculcarán los principios bioéticos. Esto puede tener una considerable influencia en la relación beneficio-riesgo de los  fármacos, pudiendo tratar a pacientes con esquemas que no aportan beneficio,  o incluso podrían perjudicarles. Por tanto, ¿hacia dónde debiera ir  orientado el proceso de humanización? Parece razonable que el beneficio del  paciente sea el objetivo fundamental del proceso de humanización de la  asistencia sanitaria, evidentemente.

Baricitinib against severe COVID-19: effectiveness and safety in hospitalised pretreated patients.

OBJECTIVES: To analyse the effectiveness and safety of baricitinib for severe COVID-19 in cytokine storm syndrome based on its potential role as an anti-inflammatory immunomodulator and inhibitor of viral endocytosis. METHODS: This was an observational retrospective study of hospitalised patients treated with baricitinib for severe COVID-19. Outcomes were clinical improvement on an ordinal scale of 1-8 on day 1 of baricitinib compared with day 14 (where 8=death and 1=not hospitalised with no limitations of activities), overall survival, time to recovery since baricitinib treatment started (days until hospital discharge) and laboratory parameters related to COVID-19 poor prognosis. Adverse events related to baricitinib during the admission period were also reported. RESULTS: Forty-three patients (70% men, mean age 70 years (IQR 54-79)) treated with baricitinib daily for 6 days (IQR 5-7) were included. Thirty-six patients were treated with corticosteroids (84%). Clinical improvement was 3 points (IQR 1-4) in patients on an ordinal scale of 4-6, overall survival was 100% at day 30 and day 60 with a mean time to recovery of 12 days (IQR 9-25) from start of baricitinib treatment. No adverse events of interest were found and all poor prognosis risk factors improved at day 14: interleukin-6, C-reactive protein, ferritin, lymphocytes, platelets and D-dimers. CONCLUSIONS: Patients treated with baricitinib for severe COVID-19 showed improvements in clinical and analytical values without relevant adverse events and 100% overall survival. Clinical randomised trials are needed to confirm the clinical benefit of baricitinib.

Healthcare Resource Utilization among Patients between 60-75 Years with Secondary Acute Myeloid Leukemia Receiving Intensive Chemotherapy Induction: A Spanish Retrospective Observational Study.

BACKGROUND: Information regarding the impact on healthcare systems of secondary acute myeloid leukemia (sAML) is scarce. METHODS: A retrospective review of medical charts identified patients aged 60-75 years with sAML between 2010 and 2019. Patient information was collected from diagnosis to death or last follow-up. Outpatient resource use, reimbursement, frequency and duration of hospitalization, and transfusion burden were assessed. Forty-six patients with a median age of 64 years were included. Anthracycline plus cytarabine regimens were the most common induction treatment (39 patients, 85%). The ratio of the total days hospitalized between the total follow-up was 29%, with a sum of 204 hospitalizations (average four/patient; average duration 21 days). The total average reimbursement was EUR 90,008 per patient, with the majority (EUR 77,827) related to hospital admissions (EUR 17,403/hospitalization). Most hospitalizations (163, mean 22 days) occurred in the period before the first allogeneic hematopoietic stem cell transplant (alloHSCT), costing EUR 59,698 per patient and EUR 15,857 per hospitalization. The period after alloHSCT (in only 10 patients) had 41 hospitalizations (mean 21 days), and a mean reimbursement cost of EUR 99,542 per patient and EUR 24,278 per hospitalization. In conclusion, there is a high consumption of economic and healthcare resources in elderly patients with sAML receiving active treatments in Spain.

Pharmacotherapeutic management of advanced therapy drugs.

Advanced therapy drugs have emerged in recent years as new pharmacotherapeutic strategies. In this context, hospital pharmacy services have had to adapt to the new challenges posed by the  inclusion of advanced therapies in their roster of services against the  background of the complex pharmacotherapeutic process patients typically go through.All the activities carried out in the hospital pharmacy services must abide by  the rules established in the Spanish legislation and ensure both the quality of  the different drugs they manage and the safety of every single patient.Advanced therapy drugs are associated certain peculiarities, including the need  to select and evaluate potential candidates to receive them; recourse to  financing mechanisms based on risk sharing; and their extreme fragility, which  means that the personnel in charge of handling them must be properly trained  to maintain their viability and that special storage conditions, involving  temperatures below 180 ºC in the case of chimeric antigen receptor T cell  therapies, must be maintained. In addition, use of advanced therapy  medications in the clinical setting has made it necessary for scientific societies  to produce consensus documents recognizing the pivotal role of hospital  pharmacists as indispensable members of the multidisciplinary healthcare team  and ensuring the same traceability, conservation, custody and  pharmacotherapeutical monitoring standards imposed on other drugs to  provide for adequate pharmaceutical care. Scientific societies have also  highlighted the importance of intensifying clinical research, an essential  requirement for the safe incorporation of new therapeutic targets. The present  document is intended to describe the challenges pharmacists may face when  using advanced therapy drugs at the different stages or processes in the  patient's clinical journey.

Los medicamentos de terapia avanzada han emergido en los últimos años  como nuevas estrategias farmacoterapéuticas. En este contexto, los servicios de farmacia hospitalaria nos hemos tenido que adaptar al nuevo reto que ha supuesto su inclusión en nuestra cartera de servicios dentro del  complejo proceso farmacoterapéutico en el que están inmersos los pacientes. Todas las actividades que se desarrollan en los servicios de farmacia hospitalaria cumplen con una base legal establecida en nuestra  legislación y garantizan la calidad y seguridad tanto de los pacientes atendidos  como de todos y cada uno de los medicamentos que se gestionan. Los  medicamentos de terapia avanzada tienen unas características especiales a  considerar que van desde las fases iniciales de selección y evaluación de los  pacientes candidatos y su modelo de financiación, basado en riesgo  compartido, hasta una fragilidad en su manipulación que requiere de una  adecuada y adaptada formación del personal implicado en la logística para  mantener su viabilidad, al necesitar unas condiciones de conservación, en  ocasiones, a temperaturas de menos 180 ºC, en el caso de las células T con  receptores quiméricos de antígenos. Además, la utilización clínica de los  medicamentos de terapia avanzada ha necesitado de documentos de consenso  de las sociedades científicas que pongan en valor el posicionamiento del  farmacéutico hospitalario, como miembro indispensable dentro del equipo  multidisciplinar asistencial, y que garanticen, como en cualquier otro  medicamento, la trazabilidad, la correcta conservación y custodia y el  seguimiento farmacoterapéutico asociado a una adecuada atención  farmacéutica de nuestros pacientes, sin olvidar la importancia de la creciente  investigación clínica, necesaria e imprescindible para una incorporación segura  de nuevas dianas terapéuticas. Por todo ello, consideramos necesario el  presente documento, en donde se ponen de manifiesto los retos o necesidades, desde el punto de vista farmacéutico, en cada una de las etapas o procesos a  considerar en la utilización de los medicamentos de terapia avanzada dentro de nuestro amplio arsenal terapéutico.

NUTRARET: Effect of 2-Year Nutraceutical Supplementation on Redox Status and Visual Function of Patients With Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Trial.

Oxidative stress plays a major role in the pathogenesis of retinitis pigmentosa (RP). The main goal of this study was to evaluate the effect of 2-year nutritional intervention with antioxidant nutraceuticals on the visual function of RP patients. Secondly, we assessed how nutritional intervention affected ocular and systemic redox status. We carried out a randomized, double-blind, placebo-controlled study. Thirty-one patients with RP participated in the study. RP patients randomly received either a mixture of nutraceuticals (NUT) containing folic acid, vitamin B6, vitamin A, zinc, copper, selenium, lutein, and zeaxanthin or placebo daily for 2 years. At baseline and after 2-year of the nutritional supplementation, visual function, dietetic-nutritional evaluations, serum concentration of nutraceuticals, plasma and aqueous humor concentration of several markers of redox status and inflammation were assessed. Retinal function and structure were assessed by multifocal electroretinogram (mfERG), spectral domain-optical coherence tomography (SD-OCT) and automated visual field (VF) tests. Nutritional status was estimated with validated questionnaires. Total antioxidant capacity, extracellular superoxide dismutase (SOD3), catalase (CAT), and glutathione peroxidase (GPx) activities, protein carbonyl adducts (CAR) content, thiobarbituric acid reactive substances (TBARS) formation (as indicator of lipid peroxidation), metabolites of the nitric oxide (NOX) and cytokine (interleukin 6 and tumor necrosis factor alpha) concentrations were assessed by biochemical and immunological techniques in aqueous humor or/and blood. Bayesian approach was performed to determine the probability of an effect. Region of practical equivalence (ROPE) was used. At baseline, Bayesian analysis revealed a high probability of an altered ocular redox status and to a lesser extent systemic redox status in RP patients compared to controls. Twenty-five patients (10 in the treated arm and 15 in the placebo arm) completed the nutritional intervention. After 2 years of supplementation, patients who received NUT presented better retinal responses (mfERG responses) compared to patients who received placebo. Besides, patients who received NUT showed better ocular antioxidant response (SOD3 activity) and lower oxidative damage (CAR) than those who received placebo. This study suggested that long-term NUT supplementation could slow down visual impairment and ameliorate ocular oxidative stress.

[Handling of drugs for administration by percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis and enteral nutrition]. / Manipulación de fármacos para su administración por gastrostomía endoscópica percutánea en pacientes con esclerosis lateral amiotrófica y nutrición enteral.

Introduction: Introduction: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Its symptoms include dysphagia that may make it necessary to place a percutaneous endoscopic gastrostomy (PEG) for feeding. The administration of drugs by PEG can obstruct it, decrease the effectiveness of treatment, and increase the risk of toxicity by altering the original pharmaceutical form. Objective: to describe and analyze the degree of adequacy of the prescription of drugs administered by PEG in patients with ALS and with enteral nutrition (EN). Material and methods: the prescription of pharmacological treatment for patients with ALS who were admitted for placement of a PEG was reviewed. The degree of adequacy of the prescribed drugs was analyzed according to criteria of loss of efficacy, toxicity, risk for handler, and compatibility with EN by consulting the available scientific evidence. Results: the medical prescriptions of the treatments of 34 patients were reviewed, with a total of 307 medications (median of 9 drugs per patient, range 2-17). Via PEG 267 oral medications (median 8 per patient, range 2-15) were prescribed; 81.65 % were solid forms, and the pharmaceutical form was modified in 43 %, due to the risk of catheter occlusion, toxicity or loss of efficacy, affecting 97 % of the patients. Conclusions: patients with ALS and PEG are at risk of presenting safety problems and loss of treatment efficacy related to alteration of the original pharmaceutical form and the interaction with EN.

Introducción: Introducción: la esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa. Entre sus síntomas destaca la disfagia, que hace necesaria la colocación de una gastrostomía endoscópica percutánea (PEG) para alimentarse. La administración de fármacos por la PEG puede obstruirla, disminuir la eficacia del tratamiento y aumentar el riesgo de toxicidad, al alterar la forma farmacéutica original. Objetivo: describir y analizar el grado de adecuación de la prescripción de fármacos administrados por PEG en pacientes con ELA y con nutrición enteral (NE). Material y métodos: se revisó la prescripción del tratamiento farmacológico de los pacientes con ELA que ingresaban para la colocación de una PEG. Se analizó el grado de adecuación de los fármacos prescritos según los criterios de pérdida de eficacia, toxicidad, riesgo para el manipulador y compatibilidad con la NE, consultando la evidencia científica disponible. Resultados: se revisaron las prescripciones médicas de los tratamientos de 34 pacientes, con un total de 307 medicamentos (mediana de 9 fármacos por paciente; rango, 2-17). Se pautaron por la PEG 267 medicamentos de administración oral (mediana de 8 por paciente; rango, 2-15). El 81,65 % fueron formas sólidas y se modificó la forma farmacéutica en el 43 % por riesgo de oclusión de la sonda, toxicidad o pérdida de eficacia, afectando al 97 % de los pacientes. Conclusiones: los pacientes con ELA y con PEG tienen riesgo de presentar problemas de seguridad y de pérdida de eficacia del tratamiento relacionados con la alteración de la forma farmacéutica original y de la interacción con la NE.

Hospital pharmacist challenges in evaluation of scientific evidence and its incorporation to pharmacotherapeutic protocols through therapeutic committees in COVID-19 times.

Type 2 coronavirus pandemics that is plaguing almost all the world has caused  qualitative and quantitative strains in health systems that have had to be responded to. The lack of known vaccines and effective treatments has generated the need to  use drugs with very little evidence for their incorporation into pharmacotherapeutic  protocols agreed by the clinical team. The hospital pharmacist, within the  multidisciplinary team, has been responsible for critically evaluating the alternatives and positioning them in these protocols. Finally, some ethical and legal questions  that should be considered in this scenario are analyzed in this article.

La pandemia por coronavirus tipo 2 que está azotando prácticamente todo el mundo ha provocado en los sistemas sanitarios tensiones cualitativas y cuantitativas a las  que ha habido que dar respuesta. La inexistencia de vacunas y de tratamientos  eficaces conocidos ha generado la necesidad de utilizar fármacos con muy escasa  evidencia para su incorporación en protocolos farmacoterapéuticos consensuados  por el equipo clínico. El farmacéutico de hospital, dentro del equipo multidisciplinar,  ha sido en muchas ocasiones el responsable de evaluar críticamente las alternativas para su posicionamiento en estos protocolos. Se analizan en el presente artículo algunas cuestiones éticas y legales que deben ser consideradas en este  escenario.