The environmental quality differences between two groups of reefs in the Veracruz Reef System were evaluated. The North group of reefs is very close to Veracruz, an urban and port zone, whereas the ...South group is more isolated, with minor anthropogenic disturbances. To prove the hypothesis that the North group is more affected by anthropogenic activities, the concentrations of hydrocarbons in liver, metals and metalloids such as Se, As, Ba, Cd, Hg and V in muscle, and PAH metabolites in bile were evaluated, and related to biomarkers (transcript abundance of cytochrome P4501A, Vitellogenin, and Glutathione-S-transferase) in two species of fish: Haemulon aurolineatum and Ocyurus chysurus. H. aurolineatum presents the highest concentrations for many pollutants, but O. chysurus shows the most significant differences in pollutant concentrations and biomarkers between the two reef groups, suggesting that this species could be used as a sentinel in future studies in the Gulf of Mexico.
Pollutant concentrations and gene expression were generally higher in the North reef group. The reefs in the North are more impacted than those in the South. Probably due to discharges from the city and port of Veracruz. O. chrysurus is proposed as a sentinel species for the Gulf of Mexico. Display omitted
•Health status of the Veracruz Reef System (Southern Gulf of Mexico) was assessed.•Two species of fish (Haemulon aurolineatum and Ocyurus chrysurus) were used as sentinel species.•Pollutants (hydrocarbons, metals and metalloids) and biomarkers were analyzed in fish.•Reefs closer to the city and port of Veracruz were most affected by pollution.•One species, O. chrisurus, is better for environmental monitoring studies in reefs.
Background and importanceInhibitors of interleukin-23 (IL-23 inhibitors) have emerged as safe and effective options for the treatment of moderate-to-severe plaque psoriasis. These drugs are ...contributing to a rising standard for psoriasis outcomes through resolution of skin lesions and joint manifestations and improvement of patient quality of lifeAim and objectivesTo evaluate the effectiveness of IL-23 inhibitors in patients with moderate–severe chronic plaque psoriasisMaterial and methodsThis was an observational study including patients with moderate-to-severe psoriasis who were treated for at least 36 weeks with IL-23 inhibitors. Data collected, obtained from digital clinical history, were: demographic characteristics and previous biological therapies. The severity of plaque psoriasis was assessed by the Psoriasis Area Severity (PASI). Efficacy was evaluated by estimating the proportion of patients achieving PASI 75, PASI 90 and PASI 100 responses at weeks 16, 24 and 36. Student’s t-test for paired samples was used to determine the significant difference in outcome of patients between PASI at baseline and PASI response at weeks 16, 24 and 36. Data were analysed using IBM SPSS Statistics v.19.0ResultsA total of 35 patients were included, 21 women (60%), mean age 50.6±13.8 years. IL-23 inhibitors used were: guselkumab (n=26, 74%) and risankizumab (n=9, 26%). All patients had chronic plaque psoriasis. Most of them had previously been treated with a biologic agent (n=33, 94%). 5 patients (14%) discontinued the anti-IL23 therapy due to inefficiency. Mean PASI at baseline was 10.1±5. IL-23 inhibitors decreased mean PASI from baseline to 3±3.3 (p=0.003), 2±3 8 (p=0.001), 1.3±2.9 (p=0.001) at 16, 24 and 36 weeks, respectively. At 16 weeks, PASI 75, 90 and 100 response was achieved in 50%, 31.8% and 22.7% of patients; at 24 weeks, PASI 75, 90 and 100 response was achieved in 86.4%, 54.5% and 40.9%, whereas at 36 weeks, PASI 75, 90 and 100 response was achieved in 100%, 77.3% and 72.7% of patients, respectively.Conclusion and relevanceIL-23 inhibitors show great results in the management of moderate-to-severe psoriasis in adults. Results of this real-life study are consistent with the pivotal trials.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and ImportanceNine drugs are currently approved for the treatment of ankylosing spondylitis (AS) in adults: adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, ixekizumab, ...secukinumab, upadacitinib and tofacitinib. Tofacitinib was the last of them to receive its approval. However, there are no direct comparisons between them.Aim and ObjectivesTo establish whether the drugs approved for AS in adults can be considered equivalent therapeutic alternatives (ATE) in efficacy in AS.Material and MethodsA search of clinical trials of these drugs in adult patients with AS was conducted, phase II or III, double-blinded, controlled with another drug or placebo.Other inclusion criteria wereEndpoint: ASAS40 (a ≥40% improvement and an absolute improvement from baseline of the Assessment in SpondyloArthritis International Society).Follow-up time: 12-16 weeks.For those drugs with more than one study, a previous meta-analysis was performed using Joaquin Primo calculator. An adjusted indirect comparison (IC) of the drugs used in AS versus tofacitinib was performed using the Bucher method, using Joaquin Primo calculator. Due to lack of data in the literature and considering that therapy failure can be recovered with second lines, half of the ASAS40 value obtained in meta-analysis was taken as delta value. ATE guide was followed in order to establish a positioning.ResultsSixteen studies were included4 adalimumab, 2 golimumab, 1 infliximab, 1 certolizumab, 2 etanercept, 1 upadacitinib, 2 tofacitinib, 1 secukinumab and 2 ixekizumab. The difference in ASAS40 of the drugs before versus tofacitinib expressed as RAR (IC 95%) was: Adalimumab 4 (-6,1; 14,1), certolizumab -7,3 (-25,1; 10,5), etanercept 2 (-11,5; 15,5), golimumab -5 (-16,3; 6,3), infliximab 8,43 (-4,8; 21,6), ixekizumab -9 (-20, 6; 2,6), secukinumab -2,7 (-18,3; 12,9), upadacitinib -1,9 (-17,8; 13,9). Adalimumab, etanercept and tofacitinib are considered ATE. Infliximab, upadacitinib, secukinumab, golimumab, certolizumab, ixekizumab and tofacitinib can also be considered ATE, being the probability of clinically relevant difference <50% (most of the 95% CI is in the equivalence range) and the failure does not involve serious/irreversible damage.Conclusion and RelevanceTofacitinib and the rest of these drugs could be considered ATE. For a definitive statement, the criteria of safety and adequacy should be considered.References and/or AcknowledgementsConflict of InterestNo conflict of interest
Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The ...antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3.
To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19.
Six different concentrations of lithium, ranging 2–12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls.
These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19′s patients.
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•Antiviral, anti-inflammatory and immune-potentiating effects of lithium salts have been described.•Lithium directly inhibits the replication of SARS-CoV-2 in Vero E6 cells in a concentration-dependent manner with an IC50 of 4 mmol/L.•Syrian hamsters treated with human therapeutic doses of lithium showed a less intense disease.
Introduction
Pembrolizumab is a monoclonal antibody approved for adult patients with advanced non–small-cell lung cancer (NSCLC). Although immune related adverse events are considered to be well ...tolerated, complications may occur and discontinuation of the treatment could be required.
Case report
A 62-year old patient diagnosed with advanced non-small cell lung cancer experienced a decline in the renal function after seven cycles with pembrolizumab.
Management & outcome: After ruling out other common causes of interstitial nephritis, pembrolizumab was attributed as a cause of interstitial nephritis. At first, toxicity was managed with corticosteroids and closely monitoring the patient, but finally pembrolizumab had to be discontinued due to the kidney function did not recover.
Discussion
Renal and urinary disorders were reported in <3% of patients treated with pembrolizumab, being interstitial nephritis the most reported toxicity. The kidney damage can be a complication to consider in patients receiving pembrolizumab. Early identification of an increase in serum creatinine levels may help with prevention by establishing an effective treatment, although it may not mean a total recovery of kidney function.
Background and importanceVenetoclax and ibrutinib are relatively new drugs and are currently elective treatments according to the guidelines for patients diagnosed with high risk chronic lymphocytic ...leukaemia (CLL).Aim and objectivesTo conduct an indirect comparison of the efficacy of venetoclax (12 cycles)+obinotuzumab (6 cycles) compared with ibrutinib (until progression)+obinotuzumab (6 cycles) and its costs.Material and methodsThe clinical trials CLL14 and ILUMINATE were reviewed, and the main outcome and similarity of the population (median age, percentage of high risk patients according to the Binet or Rai classification and percentage of patients with high risk cytogenetics) were evaluated.An indirect comparison of median progression free survival (PFS), PFS at 24 months, minimal residual disease (MRD) in peripheral blood, overall survival (OS) and complete response was conducted.Lastly, the cost of both 12 and 24 months of treatment were compared.Results CLL14 ILUMINATE Venetoclax+obinotuzumab vs clorambucil+obinotuzumab Ibrutinib+obinotuzumab vs clorambucilo+obinotuzumab No of patients 432 1:1 229 1:1 Age (years) (median) 72 70 High risk (Binet/Rai) (%) 43 52 Patient with del p17 (%) 8 14 Patients with tp53 (%) 9.5 15.5 Unmutated IGHV (%) 60 757 Indirect comparison PFS HR 0.66 (95% CI 0.36 to 1.22, p=0.18) ibrutinib favoured PFS at 24 months RR 0.64 (95% CI 0.32 to 1.08, p=0.09) ibrutinib favoured MRD peripheral blood RR 1.41 (95% CI 0.85 to 2.32, p=0.18) venetoclax favoured CR RR 0.85 (95% CI 0.39 to 1.86, p=0.69) venetoclax favoured Cost Venetoclax+obinotuzumab Ibrutinib+obinotuzumab 12 months (€) 76 374 76 786 24 months (€) 76 374 127 891 Conclusion and relevanceAlthough in advance, populations could be comparable, limitations such as time of treatment with chlorambucil exist (6 months vs 12 months).No statistically significant differences were found between:o Median PFS and 24 month PFS: Beauchemin et al1 concluded that correlations between PFS and OS exist in patients previously treated, but not in naïve patients.o MDR and CR: Langerat et al2 concluded that “MRD status is associated with PFS and OS in CLL patients, and has the potential to act as a surrogate marker”.Ibrutinib cost was superior after the first year of treatment.To conclude, it is necessary to obtain OS data to conduct an indirect comparison of greater quality.References and/or acknowledgements1. DOI: 10.1182/blood-2018-03-8396882. DOI: 10.3747/co.22.2119.No conflict of interest.
5PSQ-118 Lithium therapy on hospital admission Rodriguez Jorge, M; Montero Pérez, O; Martín Fernandez, N ...
European journal of hospital pharmacy. Science and practice,
03/2022, Letnik:
29, Številka:
Suppl 1
Journal Article
Recenzirano
Odprti dostop
Background and importanceThe narrow therapeutic window of lithium (serum concentration between 0.6 and 0.8 mmmol/L) makes it essential to monitor its plasma concentrations and to watch for possible ...interactions that may lead to changes in its pharmacokinetics. Many drugs can interact with lithium, and some are used by a high percentage of the population.Aim and objectivesThe aim of this study was to assess possible interactions of lithium with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor antagonists (ARA-II) or diuretics. To intervene when necessary, and to analyse the acceptance of such interventions by the physician on hospital admission.Material and methodsA prospective analytical study was performed in a second-level hospital for a period of 8 months (1 November–30 June 2021). Every patient admitted and on treatment with lithium was included.Concomitant treatments were analysed to detect possible interactions and whether such treatments were initiated ambulatory or during the hospital stay. When interactions were detected, the pharmacist intervened by informing the physician via ATHOS-Prisma messaging and recommending a blood test for lithemia levels, in order to reduce or increase the lithium doses if necessary.ResultsA total of 35 patients were included in the study; median age 47±15 and 20 are women, 28 had lithium prescribed at home.Possible interactions were detected in 8 patients. Of these, 6 patients had both drugs interacting prescribed ambulatory and 2 had at least one of the interacting drugs prescribed by the specialist at admission.Only the interventions in those 2 patients were accepted by the physician. Both interactions were between lithium and a drug that altered renal function (ACEi/ARA-II), increasing lithium levels above their therapeutic window.Conclusion and relevancePharmacists’ interventions were only accepted when the drug was prescribed by the specialist contacted. When the drugs were prescribed ambulatory by another physician, interventions were not effective.The fact that the patient had been taking the interacting drugs before admission does not make it less important, and in light of the results, the pharmacist should try another path to intervene, such as contacting the specialist responsible or his usual doctor at discharge.In short, pharmacists are essential for detecting potential risks of toxicity due to high serum levels, and avoiding low doses, which could lead to a loss of efficacy.References and/or acknowledgementsConflict of interestNo conflict of interest
Background and importanceHazardous drugs (HD) are those that exhibit one or more of the following six characteristics in humans or animals: carcinogenicity, teratogenicity or other developmental ...toxicity, reproductive toxicity, organ toxicity at low doses, genotoxicity, and structure and toxicity profiles of new drugs that mimic existing drugs, determined hazardous by the above criteria. Exposure to HD in the workplace could lead to serious health risks, which increase with exposure frequency. Therefore, it is crucial to limit exposure with appropriate equipment.Aim and objectivesTo identify HD used in a nursing home and to analyse the use of appropriate self-protection measures by nursing staff.Material and methodsA prospective, observational study was performed in a nursing home over a 1 month period. Direct observation was carried out about how nursing staff handled HD. These drugs were identified through the medication sent to the nursing home and were categorised according to reference documentation (NIOSH and INSST (group 1, 2 or 3). Data collected were, for the nursing staff, age, sex, staff at reproductive risk and use of personal protective equipment (PPE) during HD handling. Use or not of hazardous drug waste containment was also collected.ResultsA total of 152 drugs were sent weekly to the nursing home, of which 11 were HD: acenocoumarol, bicalutamide, carbamazepine, clonazepam, spironolactone, lamivudine, paroxetine, risperidone, tacrolimus, topiramate and valproic acid (18% group 1, 36% group 2% and 46% group 3). Nursing staff comprised 24 workers, 14 women (58.3%) and 10 men (41.7%), with a median age 41 years. Personnel at reproductive risk were 10 (66.7%): 7 women and 3 men. All staff used PPE insufficiently: they did not wear double gloves when handling HD or goggles with side shields when splashing was a possibility. Waste disposal was inadequate in 100% because of containers used were incorrect.Conclusion and relevanceMishandling of HD was widespread: nursing staff did not use PPE as recommended by the administration guidelines for HD. There was no awareness of suitable waste disposal. Pharmaceutical interventions could decrease the potential risk of occupational exposure.References and/or acknowledgementsNo conflict of interest.
Background and importanceDifferent studies in the literature have demonstrated promising efficacy of cisplatin–gemcitabine for the treatment of metastatic breast cancer. Real life studies are ...commonly performed to confirm the results.Aim and objectivesTo analyse cisplatin–gemcitabine effectiveness and safety in patients with metastatic breast cancer.Material and methodsA retrospective observational study was conducted in a university hospital. Patients treated with cisplatin–gemcitabine from January 2007 to February 2020 were included. The following variables were recorded: age, hormone receptor (HR), human epidermal growth receptor-2 (HER2) status, duration of treatment, number of cycles, number and type of previous chemotherapy regimens, progression free survival (PFS) and overall survival (OS), calculated by the Kaplan–Meier method, and adverse events (AEs). Data were obtained from the electronic clinical records and the software where the chemotherapy treatments are registered.Results56 patients were included, with a median age of 56.5 years (range 30–82). 40 patients (71%) were HR positive, 13 patients (23%) were triple negative and 6 patients (11%) were HER2 positive. At the time of data analysis, one patient was still receiving treatment with cisplatin–gemcitabine and 55 had finished treatment, with a median duration of 2.8 months (4 cycles, range 1–10). Patients had a median of two previous chemotherapy lines in metastatic stage (range 0–4). 85.7% of patients received cisplatin–gemcitabine as metastatic therapy in the secondline or later. The most common regimens used before cisplatin–gemcitabine in metastatic disease were: non-pegylated–liposomal doxorubicin (54.2%), nab–paclitaxel (37.5%), paclitaxel–bevacizumab (35.4%), eribulin (27.1%), epirubicin–docetaxel (18.8%), paclitaxel monotherapy (16.7%), docetaxel monotherapy (14.6%) and pegylated–liposomal doxorubicin (12.5%), with other regimens used less frequently. Median PFS and OS were 3.4 and 6.8 months, respectively. 51.8% of patients had any AE during treatment and the most frequent were anaemia (62%), neutropenia (31%), thrombocytopenia (24%), peripheral neuropathy (17.2%) and asthenia (10.3%). Six patients interrupted their treatment due to AEs.Conclusion and relevanceCisplatin–gemcitabine was shown to be another effective treatment option in metastatic breast cancer. However, several studies in the literature have shown better results for PFS and OS. This may be due to differences in the baseline characteristics of the patients and the use of previous chemotherapy regimens. Cisplatin–gemcitabine was well tolerated and in most cases the AEs did cause interruption of treatment.References and/or acknowledgementsConflict of interestNo conflict of interest
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