Planning and diagnostic nursing strategy in the clinical management of the patient with hyperthroidism

Hyperthyroidism is a common disease that affects 0.8% of the population in Europe. It occurs when the thyroid gland produces more thyroid hormones than your body needs. There are several types of treatment, such as antithyroid drugs, treatment with radioactive iodine (131I) and finally surgery, in addition to these treatments, reference is made to a good hygienic-dietary orientation. Objective: to assess from the nursing field the safest and most effective type of hyperthyroidism treatment, including the risk factors to take into account when carrying out these. Methodology: systematic searches were carried out in bibliographic sources of trials and articles published between 2015 and 2021. Including studies that contained data on risk factors for hyperthyroidism. Results: of 426 related articles found, 13 met the inclusion criteria. Total thyroidectomy surgery induced a 26% therapeutic failure rate and 95% radioactive iodine treatment compared to the 19.1% therapeutic failure in antithyroid drug treatment. Conclusion: Despite the verification of the efficacy of all existing hyperthyroidism treatments, antithyroid drugs have greater efficacy and safety than the rest of the treatments studied, in relation to the time and rate of remission. On the other hand, risk factors such as tobacco and female sex are evidenced, which are negative factors when carrying out treatment for hyperthyroidism.

Five-Year Long-Term Follow-Up of Selective Laser Trabeculoplasty in Open-Angle Glaucoma

Purpose Selective laser trabeculoplasty (SLT) is known as a safe laser therapy for an effective reduction in intraocular pressure (IOP). The aim of this study was to examine the therapeutic success of SLT in open-angle glaucoma (OAG) patients with a long-term follow-up of 5 years. Methods Forty-six eyes of forty OAG patients, some with previous intraocular surgery, underwent SLT (24 males, 16 females). Therapeutic success was categorized as: category (I) – IOP reduction ≤ 21 mmHg and > 20% compared to baseline IOP with additional glaucoma medication; category (II) – IOP reduction ≤ 18 mmHg and > 30% compared to baseline IOP with additional glaucoma medication; category (III) – IOP reduction ≤ 18 mmHg without any additional glaucoma medication at all follow-ups. Therapeutic failure was defined as the necessity of any further glaucoma surgery (IV). Results (1) SLT was well tolerated in all eyes, and no severe side effects or complications were recorded. (2) After 1-year follow-up, therapeutic success was 27% (I), 30% (II), and 3% (III). The therapeutic failure rate was 40% (IV). (3) After 2 years follow-up, therapeutic success was 7% (I), 10% (II), and 0% (III). The therapeutic failure rate was 83% (IV). (4) After 3 years follow-up, the therapeutic failure rate increased up to 100% (IV). Conclusion SLT seemed to be effective in lowering IOP in the first year in the present cohort, however, the long-term effect is low and additional local therapy or surgical interventions are necessary.

Dose Banding -- weighing up benefits, therapeutic failure and risks

Aim Dose banding is a commonly used method of dose individualisation in which all patients with similar characteristics are allocated to the same dosing group. Dose banding results in some patients receiving less intensive treatment with the potential for a reduction in therapeutic benefit (iatrogenic therapeutic failure). This study aims to explore the effects of dose banding on therapeutic success and failure. Methods This was a simulation study conducted using MATLAB. Virtual patients were simulated under a simple pharmacokinetic model with a predefined target steady-state average concentration (c_(ss,ave)). Clearance was correlated with a covariate used for dosing. Dose individualisation was based on: one-dose-fits-all, covariate based dosing, empirical dose banding, dose banding optimised for benefit:risk only and dose banding optimised for both benefit:risk and minimising iatrogenic therapeutic failure. Results The lowest and highest probabilities of target attainment (PrTA) were 46% for one-dose-fits-all and 72% for fully individualised covariate-based dosing. Neither dosing approach would result in iatrogenic therapeutic failure as lower dose intensities do not occur. Empirical dose banding performed better than once-dose-fits-all with 59% PTA but not as good as either optimised method (64-69% PrTA) while carrying a risk of iatrogenic therapeutic failure in 25% of patients. Optimising for benefit:risk (only) improved PrTA but carried a risk of iatrogenic therapeutic failure of up to 10%. Optimising for benefit:risk and minimising iatrogenic therapeutic failure provided the best balance. Conclusion Future application of dose banding needs to consider both the probability of benefit:risk as well the risk of causing iatrogenic therapeutic failure.

Risk prediction of clinical adverse outcomes with machine learning in a cohort of critically ill patients with atrial fibrillation

Critically ill patients affected by atrial fibrillation are at high risk of adverse events: however, the actual risk stratification models for haemorrhagic and thrombotic events are not validated in a critical care setting. With this paper we aimed to identify, adopting topological data analysis, the risk factors for therapeutic failure (in-hospital death or intensive care unit transfer), the in-hospital occurrence of stroke/TIA and major bleeding in a cohort of critically ill patients with pre-existing atrial fibrillation admitted to a stepdown unit; to engineer newer prediction models based on machine learning in the same cohort. We selected all medical patients admitted for critical illness and a history of pre-existing atrial fibrillation in the timeframe 01/01/2002–03/08/2007. All data regarding patients’ medical history, comorbidities, drugs adopted, vital parameters and outcomes (therapeutic failure, stroke/TIA and major bleeding) were acquired from electronic medical records. Risk factors for each outcome were analyzed adopting topological data analysis. Machine learning was used to generate three different predictive models. We were able to identify specific risk factors and to engineer dedicated clinical prediction models for therapeutic failure (AUC: 0.974, 95%CI: 0.934–0.975), stroke/TIA (AUC: 0.931, 95%CI: 0.896–0.940; Brier score: 0.13) and major bleeding (AUC: 0.930:0.911–0.939; Brier score: 0.09) in critically-ill patients, which were able to predict accurately their respective clinical outcomes. Topological data analysis and machine learning techniques represent a concrete viewpoint for the physician to predict the risk at the patients’ level, aiding the selection of the best therapeutic strategy in critically ill patients affected by pre-existing atrial fibrillation.

Early Experiences in Switching between Monoclonal Antibodies in Patients with Nonresponsive Migraine in Spain: A Case Series

Monoclonal antibodies targeting the calcitonin gene-related peptide have been introduced into the therapeutic arsenal of migraine prophylaxis. Clinical trials report similar efficacy between them, and there is no evidence of switching to another one after failure. We aim to describe our experience in switching from erenumab to galcanezumab after therapeutic failure. We retrospectively reviewed 30 migraine patients who received monoclonal antibodies, with 15 of them switched after failure to achieve reduction in migraine days per month ≥30%. A ≥30% reduction in migraine days per month compared to baseline was observed in 8/15 (4/15 ≥ 50%) patients after switch. Some nonresponsive patients may benefit from switching between monoclonal antibodies with different therapeutic targets.

A High Rate of Recurrent Vulvovaginal Candidiasis and Therapeutic Failure of Azole Derivatives Among Iranian Women

Recurrent vulvovaginal candidiasis (RVVC) is one of the most prevalent fungal infections in humans, especially in developing countries; however, it is underestimated and regarded as an easy-to-treat condition. RVVC may be caused by dysbiosis of the microbiome and other host-, pathogen-, and antifungal drug-related factors. Although multiple studies on host-related factors affecting the outcome have been conducted, such studies on Candida-derived factors and their association with RVVC are lacking. Thus, fluconazole-tolerant (FLZT) isolates may cause fluconazole therapeutic failure (FTF), but this concept has not been assessed in the context of Candida-associated vaginitis. Iran is among the countries with the highest burden of RVVC; however, comprehensive studies detailing the clinical and microbiological features of this complication are scarce. Therefore, we conducted a 1-year prospective study with the aim to determine the RVVC burden among women referred to a gynecology hospital in Tehran, the association of the previous exposure to clotrimazole and fluconazole with the emergence of FLZT and fluconazole-resistant (FLZR) Candida isolates, and the relevance of these phenotypes to FTF. The results indicated that about 53% of the patients (43/81) experienced RVVC. Candida albicans and C. glabrata constituted approximately 90% of the yeast isolates (72 patients). Except for one FLZT C. tropicalis isolate, FLZR and FLZT phenotypes were detected exclusively in patients with RVVC; among them, 27.9% (12/43) harbored FLZR strains. C. albicans constituted 81.2% of FLZR (13/16) and 100% of the FLZT (13/13) isolates, respectively, and both phenotypes were likely responsible for FTF, which was also observed among patients with RVVC infected with fluconazole-susceptible isolates. Thus, FTF could be due to host-, drug-, and pathogen-related characteristics. Our study indicates that FLZT and FLZR isolates may arise following the exposure to over-the-counter (OTC) topical azole (clotrimazole) and that both phenotypes can cause FTF. Therefore, the widespread use of OTC azoles can influence fluconazole therapeutic success, highlighting the necessity of controlling the use of weak topical antifungals among Iranian women.

Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.

CYP2D6 Genetic Variation and Its Implication for Vivax Malaria Treatment in Madagascar

Plasmodium vivax is one of the five human malaria parasite species, which has a wide geographical distribution and can cause severe disease and fatal outcomes. It has the ability to relapse from dormant liver stages (hypnozoites), weeks to months after clearance of the acute blood-stage infection. An 8-aminoquinoline drug primaquine (PQ) can clear the hypnozoites, and thus can be used as an anti-relapse therapeutic agent. Recently, a number of studies have found that its efficacy is compromised by polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene; decreased or absence of CYP2D6 activity contributes to PQ therapeutic failure. The present study sought to characterize CYP2D6 genetic variation in Madagascar, where populations originated from admixture between Asian and African populations, vivax malaria is endemic, and PQ can be deployed soon to achieve national malaria elimination. In a total of 211 samples collected from two health districts, CYP2D6 decreased function alleles CYP2D6*10, *17, *29, *36+*10, and *41 were observed at frequencies of 3.55–17.06%. In addition, nonfunctional alleles were observed, the most common of which were CYP2D6*4 (2.13%), *5 (1.66%), and the *4x2 gene duplication (1.42%). Given these frequencies, 34.6% of the individuals were predicted to be intermediate metabolizers (IM) with an enzyme activity score (AS) ≤ 1.0; both the IM phenotype and AS ≤ 1.0 have been found to be associated with PQ therapeutic failure. Furthermore, the allele and genotype frequency distributions add to the archaeological and genomic evidence of Malagasy populations constituting a unique, Asian-African admixed origin. The results from this exploratory study provide fresh insights about genomic characteristics that could affect the metabolism of PQ into its active state, and may enable optimization of PQ treatment across human genetic diversity, which is critical for achieving P. vivax elimination.

Interim and end-treatment 18F-Fluorocholine PET/CT and bone scan in prostate cancer patients treated with Radium 223 dichloride

To assess the predictive and prognostic aim of interim and end-treatment 18F-fluorocholine PET/CT (FCH-PET/CT) and 99mTc-methilen diphosphonate bone scintigraphy (BS) in patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with Radium 223 dichloride (223Ra). Prospective and multicentre ChoPET-Rad study including 82 patients with CRPC-BM. Baseline, after 3 (interim) and 6 doses (end-treatment) BS and FCH PET/CT were performed in patients who meet the study criteria. Clinical variables, imaging and clinical progression were obtained and their association with progression free survival (PFS), and overall survival (OS) was studied. Agreement between BS and FCH PET/CT response was assessed using Kappa (K) analysis. Median of PFS and OS was 3 and 16 months, respectively. Agreement between interim BS and FCH PET/CT was weak (K: 0.28; p = 0.004). No agreement was observed between end-treatment diagnostic studies. Interim and end-treatment FCH PET/CT were related to PFS (p = 0.011 and p < 0.001, respectively). Therapeutic failure and interim BS and FCH PET/CT showed association with OS (p < 0.001, p = 0.037 and p = 0.008, respectively). Interim and end-treatment FCH PET/CT were good predictors of biochemical progression in patients treated with 223Ra. Therapeutic failure and progression in interim BS or FCH PET/CT were adverse factors for OS.