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Direct oral anticoagulants (DOACs) represent a new generation of drugs that have been increasingly used in the prevention and treatment of thromboembolic states. According to the mechanism of anticoagulant action, DOACs are divided into two groups: direct inhibitors of thrombin (dabigatran) and direct inhibitors of activated factor X (FXa) (rivaroxaban, apixaban, edoxaban, betrixaban). Compared to the vitamin K antagonists, DOACs are superior in terms of onset of action, pharmacokinetic and pharmacodynamics properties and fixed daily dose without the need for routine coagulation monitoring. Despite these advantages, there are clinical conditions in which laboratory measurement of DOACs should be performed. Although DOACs have an impact on screening haemostasis assays (prothrombin time, PT; activated partial thromboplastin time, aPTT; and thrombin time, TT), these tests are not appropriate for quantifying drug levels. Therefore, specific quantitative methods (LC-MS/MS as a gold standard method for all DOACs, coagulometric and chromogenic assays for dabigatran, and chromogenic anti-Xa assays with drug-specific calibrators for inhibitors of FXa) should only be used for determination of DOACs concentration. The aim of this review is to present all aspects of laboratory assessment of DOACs, including pre-analytical, analytical and post-analytical factors in the overall testing process with a special accent on the available specific quantitative methods for measurement of DOACs in circulation.

A significant barrier to the usage of isotretinoin has been concerns regarding its adverse effect profile. The dose-dependent mucocutaneous side effects of isotretinoin are well recognized and easily managed, particularly if a lower dose is used. A possible association with depression has gained widespread media attention and is a source of concern for many patients and their carers, but data from prospective studies and recent meta-analyses have been reassuring. Furthermore, there has been much confusion amongst both patients and physicians regarding a possible association with inflammatory bowel disease, as well the ocular and rheumatological adverse effects of isotretinoin. We provide an update on the evidence surrounding the adverse effects of isotretinoin and discuss practical strategies to prevent and manage these adverse effects. We also discuss appropriate laboratory monitoring for patients taking isotretinoin.

Apremilast, an oral phosphodiesterase-4 inhibitor, is approved for use in the management of psoriasis and psoriatic arthritis. Although its efficacy and safety have been well established in clinical studies, in real-world settings, different practice scenarios have been reported. This review paper serves to evaluate clinical real-world scenarios and aspects of treatment for which the information in the literature was considered to be lacking or controversial. Following a literature review, a panel of five dermatologists with expertise in psoriasis considered five scenarios; namely, the positioning of apremilast in psoriasis, its use in difficult-to-treat areas, special conditions and populations, safety, dose titration and dose in maintenance therapy. These were then assessed with psoriasis experts in India using a web-based questionnaire. A total of 28 questions were discussed regarding these scenarios. According to the responses, apremilast is effective in stable mild to moderate psoriasis as monotherapy and in severe psoriasis in combination. Also, a positive response was received with regard to its effectiveness in difficult locations such as the scalp, palms and soles. To reduce adverse effects, prolonged titration therapy over 4 weeks is required and lower doses can be prescribed to maintain remission. Apremilast therapy should be continued for a minimum of 8 weeks once initiated to achieve the desired results, and the total duration of therapy should be about 24 weeks for better efficacy. It is also effective in many other cases, such as obese patients, patients with hepatitis B or C and HIV, or patients on polypharmacy. It was also reported that apremilast requires less prescreening and monitoring than other conventional and biologic systemic therapies. Overall, apremilast is an attractive option for the individualized treatment of psoriasis owing to its favorable safety profile, its ease of oral administration without the need for screening or ongoing laboratory monitoring, and its positive impact on symptoms and lesions in difficult-to-treat areas.

A cirurgia bariátrica é uma opção terapêutica no tratamento da obesidade em doentes, selecionados cuidadosamente, com perturbação psiquiátrica. Cerca de metade dos doentes referenciados para cirurgia bariátrica têm diagnosticada, pelo menos, uma perturbação mental, estando a maioria medicada com psicofármacos. Este procedimento pode alterar significativamente a biodisponibilidade dos fármacos e o lítio não é exceção. Contudo, apesar da absorção parecer diminuir na maioria dos fármacos, no caso do lítio existe um elevado risco de toxicidade. Neste artigo, descreve-se o caso de uma doente de 44 anos com um quadro de intoxicação por lítio pós-cirurgia bariátrica. Realizou-se uma revisão dos casos clínicos descritos na literatura de toxicidade ao lítio pós-cirurgia bariátrica e apresentam-se potenciais soluções clínicas preventivas. É essencial uma maior consciencialização das alterações na absorção dospsicofármacos pós-cirurgia, particularmente no caso do lítio. Recomenda-se fortemente uma monitorização, de forma mais regular, pós-cirúrgica clínica e laboratorial dos níveis séricos de lítio.

Introduction Real-world data on prophylaxis of severe haemophilia A (HA) patients treated by emicizumab are scarce. Aim To study the efficacy and safety of longitudinal emicizumab prophylaxis and assess laboratory monitoring correlations in a large patient cohort. Methods HA patients with and without FVIII inhibitors, initiating emicizumab prophylaxis, were prospectively enrolled. Bleeding, adverse events and surgeries were documented. FVIII inhibitors, emicizumab levels and thrombin generation (TG) were sequentially measured. Results A total of 107 patients, including 58 children (whose median (IQR) age was 6 (1-11) years) with severe HA, composed the study cohort. Twenty-nine per cent (31/107) of our HA patients had FVIII inhibitors. Patients were followed for a median of 67 weeks (up to 144 weeks). Fifty-three patients, whose median follow-up was 53 weeks, experienced zero bleeds. Most bleeds (94%) among children were trauma-related, whereas 61% of adults sustained spontaneous joint bleeds. Four patients experienced major bleeds, with a fatal outcome in one infant, who also presented with central venous line thrombosis. No other serious adverse events were encountered. Seven patients have decided to stop emicizumab treatment for various reasons. Emicizumab plasma levels increased after emicizumab prophylaxis initiation, and values were maintained during follow-up, in all but one patient, suspected of anti-drug antibodies. A significant reduction of FVIII inhibitor levels was noted among inhibitor patients. TG was increased and sustained yet could not prognosticate bleeding risk. Conclusion Emicizumab prophylaxis was mostly well tolerated, although 50% of patients experienced breakthrough bleeds. Routine TG monitoring is not obligatory, and further studies are warranted in selected patient populations.

Introduction. Poultry meat and eggs represent a risk of contamination with zoonotic bacterial agents. This requires permanent laboratory monitoring throughout the production chain segment. Material and methods. The research material consisted of samples retrieved from poultry carcasses and eggs for current consumption. There were examined 80 samples of eggs and 110 samples of poultry carcasses. Results. S. Gallinarum, S. Enteritidis and S. Infantins serotypes were isolated in 12.7% of samples out of 110 examined carcasses, whereas S. Gallinarum, S. Dublin și S. Typhimurium serotypes were detected in 6.25% of 80 egg samples. Conclusions. Bacteriological research on poultry carcasses and eggs showed the presence of pathogenic serotypes of Salmonella spp., which is a major risk to public health.

A raíz de la pandemia generada por el SARS-CoV-2, los sistemas de salud de los distintos países han experimentado un dramático aumento en la ocupación de las unidades de cuidado intensivo y, por ende, una alta demanda de ventiladores mecánicos. En este artículo se propone un protocolo de pruebas de ventiladores mecánicos de bajo costo en modelos porcinos, como parte del desarrollo de equipos biomédicos que pueden apoyar la crisis sanitaria suscitada por la pandemia. El protocolo aborda aspectos que incluyen la fase previa a la prueba, el manejo anestésico, de vía aérea, seguimiento de laboratorio, recuperación y seguimiento del animal. Como resultado, se presenta a la comunidad académica un protocolo de validación de prototipo de ventilador mecánico en espécimen porcino como un referente para su aplicación y revalidación por parte de grupos interesados en el desarrollo de tecnologías locales de bajo costo.

Home specimen self-collection kits with central laboratory testing may improve persistence with PrEP and enhance telehealth programs. We offered Iowa TelePrEP clients the choice of using a home kit or visiting a laboratory site for routine monitoring. Mixed-methods evaluation determined the proportion of clients who chose a kit, factors influencing choice, associations between kit use and completion of indicated laboratory monitoring, and user experience. About 46% (35/77) chose to use a kit. Compared to laboratory site use, kit use was associated with higher completion of extra-genital swabs (OR 6.33, 95% CI 1.20-33.51, for anorectal swabs), but lower completion of blood tests (OR 0.21, 95% CI 0.06-0.73 for creatinine). Factors influencing choice included self-efficacy to use kits, time/convenience, and privacy/confidentiality. Clients reported kit use was straight-forward but described challenges with finger prick blood collection. Telehealth PrEP programs should offer clients home kits and support clients with blood collection and kit completion.Los kits de pruebas caseras de auto-recolección junto con los ensayos de laboratorio central puedan mejorar la persistencia de PrEP y aumentar los programas de telesalud. Ofrecimos a los clientes de Iowa TelePrEP la opción de o utilizar un kit de pruebas caseras o visitar un sitio de laboratorio para seguimiento rutinario.La evaluación de métodos mixtos determinó la proporción de los clientes que eligieron un kit, los factores que influyen en la elección, las asociaciones entre el uso del kit y la realización del monitoreo de laboratorio indicado y la experiencia de los usuarios. Casi 46 % (35 de 77) eligió utilizar un kit. Comparado con el uso del sitio de laboratorio, el kit fue asociado con mayores tasas de terminación para los hisopos extragenitales (OR 6.33, 95% CI 1.20-33.51, para hisopos anorectales), pero menores tasas de terminación para los análisis de sangre (OR 0.21, 95% CI 0.06-0.73 para creatinina). Los factores que influyeron en la elección incluyeron la autoeficacia para usar los kits, el tiempo / la comodidad y la privacidad/ confidencialidad. Los clientes informaron que el uso del kit fue sencillo pero describieron desafíos con la recolección de sangre por un pinchazo. Los programas de PrEP de telesalud deben ofrecer a los clientes kits para el hogar y apoyarlos con la recolección de sangre y la terminación del kit.

Central diabetes insipidus (CDI) may occur in the setting of intracranial abnormalities that affect the hypothalamus-pituitary system. It occurs rarely in neonates, especially in the premature population, and represents a challenging disease process to treat pharmacologically. Little is known regarding the treatment options in premature infants, including dose and route of administration of intravenous desmopressin (DDAVP). We present a case of a late premature male infant with gastroschisis and septo-optic dysplasia who developed transient CDI. He was treated with intravenous DDAVP but required frequent laboratory monitoring and a multidisciplinary approach, and ultimately his CDI resolved. Although there are minimal guidelines regarding the appropriate formulation and dosage of DDAVP for management of CDI in infants, we initiated the lowest dose available and titrated the medication based on close monitoring of urine output and serum sodium levels in order to successfully treat his transient CDI.

Taking recent publications into account, one should consider avoiding routine use of hydroxychloroquine, especially if combined with azithromycin, for COVID-19. Such treatment may be associated with the increased risk for hospital mortality and QT prolongation, while there is no documented effectiveness regarding SARS-CoV-2 clearance and outcomes. This treatment may be considered in individual cases, provided potential benefit and risks are carefully weighted, and safety monitoring is enhanced. Hydroxychloroquine safety in outpatients with COVID-19 is poorly studied and risks are increased by challenges in monitoring QT and electrolytes, hence hydroxychloroquine cannot be considered as first line treatment in outpatient settings. Such use of hydroxychloroquine is not recommended if clinical, instrumental, and laboratory monitoring are not in place.

Purpose The results of a study to determine the difference in HIV management with clinical pharmacist input in an adult psychiatric hospitalized patient population are reported. Methods Single-center, retrospective study of patients admitted to a psychiatric hospital on antiretroviral (ARV) medication(s) from October 2016 to March 2017 (phase I: no pharmacist involvement), October 2017 to March 2018 (phase II: partial pharmacist involvement), and November 2018 to January 2019 (phase III: consistent pharmacist involvement). Patients were excluded if less than 18 years of age, pregnant, incarcerated, or taking ARV medication(s) for non-HIV indications. The primary outcome was difference in appropriateness of ARV therapy prior to and during pharmacist involvement. Secondary outcomes were appropriateness of opportunistic infection (OI) prophylaxis, laboratory testing, and comprehensive HIV management. Results Thirty-seven patients were included per phase. An increased number of appropriate ARV regimens were initiated in phase II compared to phase I (62% vs 32%; P = 0.01) and in phase III compared to phase II (84% vs 62%; P = 0.036). Increased laboratory monitoring was seen with partial and consistent pharmacist involvement. Among the patients requiring OI prophylaxis, appropriate prophylaxis was initiated in more patients in phase III (57%) than in phase II (50%) or phase I (11%). More patients had comprehensive HIV management in phase II compared to phase I (38% vs 5%; P < 0.001) and in phase III compared to phase II (46% vs 38%; P = 0.48). Conclusion Pharmacist involvement in HIV management in a psychiatric patient population increased appropriateness of ARV therapy, laboratory testing, and OI prophylaxis.

Congenital hypothyroidism is a condition resulting from a deficiency of thyroid hormone in newborns. Congenital hypothyroidism has no specific signs and symptoms at birth. It may lead to severe mental retardation and growth, and developmental disorders. Therefore, it is essential to perform newborn laboratory screening tests for prompt diagnosis and treatment to minimize the sequels. Laboratory screening tests are performed by taking prick blood from the heel of newborn and testing either TSH or T4 or both of them. Currently, the congenital hypothyroidism screening is not mandatory in Indonesia, but some multicentered screening programs have been performed. In Indonesia, a TSH level above 20 µU/mL is used as a cutoff that needs a confirmatory test using serum samples to confirm congenital hypothyroidism diagnosis. Once the diagnosis is established, prompt treatment and laboratory monitoring are needed for a better outcome.

At the present stage, carrying out laboratory monitoring of the presence and concentrations of all known harmful chemicals within the framework of socio-hygienic monitoring is technically impossible, due to their extremely large number. At the same time, for most chemical compounds and elements, the nature and degree of their impact on human health, as well as the pathologies caused by them, have been scientifically established [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. The so-called ecologically dependent diseases are most determined with environmental quality parameters [11]. The paper presents the results of the use of an inter-regional comparative analysis of the incidence of the child population by individual environmentally dependent pathologies, which makes it possible to identify priority classes of diseases and nosological forms for the region, the occurrence and development of which is caused by air pollution. Considering the nature of the incidence of these pathological conditions as an indicator of the possible presence of harmful substances in the atmospheric air, this approach can be used to compile a list of priority pollutants to be controlled in a particular region, which will increase the reliability of assessing the quality of the air environment in the framework of social and hygienic monitoring.

This article presents a retrospective analysis of the laboratory monitoring orders from the specialized clinical laboratory. It has been established that large amounts of information about rare, poorly understood diseases and special types of pathology are accumulated during the everyday activity of specialized clinical laboratory. This research indicated that the share of laboratory monitoring, with 17 % of all orders, has a tendency to increase, which may be associated with the improvement of laboratory diagnostic methods. The possibility of laboratory monitoring results using in order to facilitate diagnostic process by the means of an optimal examination algorithm compiling, as well as to study regional pathology, is discussed. Besides, the prospects of using information on laboratory monitoring in improving the organization of specialized clinical laboratory’s activity are assessed.

What is known and objective Immune checkpoint inhibitors can cause immune‐related adverse events (irAEs). Improved monitoring systems for irAEs, which include laboratory tests by a qualified multidisciplinary team, might prevent patients from irAE‐associated events. Kobe City Medical Center General Hospital developed protocol‐based pharmacist‐facilitated laboratory tests named protocol‐based pharmacotherapy management (PBPM) to aid the administration of immunotherapy to patients with lung cancer. The protocol defines the laboratory test items and times at which they should be performed. It requires pharmacists to check laboratory orders initiated by physicians and enter additional test items if the orders are incomplete. We evaluated the efficacy of PBPM in irAE monitoring and compared it with those of conventional care systems. Methods From January 2016 to March 2018, 114 patients with lung cancer received immunotherapy, which was managed by conventional care (conventional group). From April to September 2018, 62 patients were managed by PBPM (PBPM group), among those 28 patients were transited from conventional group to PBPM group. Data on whether the laboratory tests were conducted or omitted were collected retrospectively for the conventional group and prospectively for the PBPM group. Results Within the conventional group, 4604 (87.6%) out of the 5253 laboratory test items were ordered by physicians. Of the remaining 649 test items, 224 (4.3%) items were added by physicians based on recommendations by pharmacists. However, of the 1581 (86.6%, from among 1826) test items that were previously ordered by physicians, only 231 (12.7%) test items were added by pharmacists. The execution rate was found to be significantly higher in the PBPM group (99.2% vs 91.9%, P, We developed protocol‐based pharmacist‐facilitated laboratory tests named protocol‐based pharmacotherapy management (PBPM) to aid the administration of immunotherapy to patients with lung cancer. Our monitoring systems provided higher executing rate of laboratory order to monitor irAEs during immunotherapy.

Measles vaccination In Russian Federation was introduced in 1967. It was assumed that the twodose vaccination regime would lead to a decrease in the incidence and elimination of measles. A number of studies have shown that up to 10% of individuals who received two doses of measles vaccine do not develop a specific humoral immunity, or do not maintain it at a protective level. This fact may contribute to gradual accumulation of persons susceptible for measles infection in the population, thus leading to emergence of new viral outbreaks in the future. The aim of this study was to perform dynamic monitoring of the post-vaccination measles immunity. The study involved 149 people. All the examined persons were divided into 2 groups. The group of comparison included persons, aged 19 to 51 years, in whom absence of measles immunity was serologically confirmed (n = 76). This group was twice vaccinated with live measles culture vaccine (NPO “Microgen”, Russia). Determination of IgG to measles virus was carried out 1 month after vaccination and revaccination. The control group consisted of persons with documented evidence of double immunization against measles virus, with laboratory-confirmed measles immunity (n = 73), aged 19 to 53 years. The comparative dynamics of development and contents of antibodies in the comparison-control groups were considered, with respect to the WHO age classification. Basic and postvaccinal dynamic determination of IgG to measles virus in serum was performed by ELISA using the “VectoKor-IgG” test system (Vector-Best, Novosibirsk). When analyzing the results of the study, it was noted that the level of measles immunity group in older persons from control group (over 45 years old) was initially higher, than in younger subjects. Among young people, the titers of specific measles antibodies reached the values of the control group of the corresponding age after the first vaccination, whereas the level of specific measles antibodies in older age group was significantly lower compared to the control group even after revaccination. A month after the first immunization, 4 people did not reach the protective level of anti-measles IgG. However, revaccination allowed them to form anti-measles immunity. In the course of our work, a case of non-response to vaccination was identified. Thus, our study showed a sufficient interindividual variability in humoral immune responses to measles vaccination.

Monitoring factor VIII (FVIII) activity has traditionally been complicated by discrepancies between assays for the various sorts of FVIII molecules. The advent of novel nonfactor therapies (emicizumab, fitusiran, and anti-tissue factor pathway inhibitor antibodies) in hemophilia A poses a new level of difficulty on the laboratory monitoring of these patients. To use the correct assays and for a proper interpretation of their results, it is pertinent to understand the mode of action of these nonfactor agents. Furthermore, the biochemical consequences for the different types of activity assays (whether it be specific FVIII activity assays or global coagulation assays) should be taken into account as well. In this review, these aspects will be discussed. In addition, the use of various animal models to estimate FVIII-equivalence of the nonfactor therapies will be presented.

Objective: To examine laboratory testing adherence by persons initiating an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). Methods: Population-based health administrative and laboratory data were accessed in British Columbia, Canada, to identify everyone filling their first prescription for dimethyl fumarate (DMF), fingolimod or teriflunomide (2011–2015). The proportion of people adherent to each drug monograph’s recommended laboratory monitoring schedule, pre- and on-DMT, was estimated. The association between patient characteristics and adherence was examined using multivariable logistic regression. Results: A total of 1016 people were included (DMF 567, fingolimod 253 and teriflunomide 196). The proportions of people adherent to pre-DMT liver and lymphocyte tests ranged from 88% to 91% and 91% to 94%, respectively, while 77% adhered to pre-DMF urinalysis. Adherence to the first on-DMT liver test was 89% for DMF (within 6 months), 61% for fingolimod (within 3 months) and 40% for teriflunomide (within 1 month). Men were less likely than women to have pre-DMF urinalysis (adjusted odds ratio (aOR); 95% confidence interval (CI): 0.40–0.95) or on-DMF liver (aOR: 0.46; 95% CI: 0.23–0.95) or lymphocyte (aOR: 0.47; 95% CI: 0.22–0.98) tests. Conclusions: Adherence to recommended laboratory testing was high (>77%) before oral DMT initiation, but lower once on drug. There is a need to understand the long-term consequences of suboptimal laboratory monitoring and sex differences in the DMT-treated MS population.

Dimorphic endemic fungi exist as mold and yeast forms at room and body temperature within the host, respectively. Primary infection can arise from new environmental exposure and less frequently through organ transplantation. Reactivation of latent infection can occur when immunosuppression is introduced or intensified. Transplant and immunocompromised hosts (ICH) represent important populations at risk for complicated and disseminated forms of endemic mycoses (EM). Diagnosis is challenging as immunosuppression contributes to insidious clinical presentations resulting in diagnostic and treatment delays. Herein, we present updated diagnosis and prevention strategies for EM in the potential organ donor, transplant candidate and recipient, and ICH. Several EM have previously been considered as restricted to a limited geographical area; however, factors such as global warming, changing precipitation patterns, and increased travel are actively expanding the geographical distribution of endemic fungi. Serological testing, often used in the immunocompetent host, has significant limitations in transplant recipients and ICH. Fungal molecular methods have emerged as an important complementary diagnostic strategy for EM but would benefit from greater standardization and wider availability. High clinical suspicion and a multipronged diagnostic approach are recommended for timely diagnosis and prevention of complications. In ICH, combining diagnostic methods increases diagnostic yield for EM. Immunosuppression-specific risk assessment, laboratory monitoring, and targeted antifungal prophylaxis are pivotal to reduce EM burden. The use of molecular methods for early diagnosis and the role of newer azoles and immunomodulation in the management of EM require further investigation.

Medical care during the Coronavirus 2019 global pandemic required significant shifts in health care delivery systems. Telehealth was widely deployed but was of limited utility for patient populations who rely heavily on laboratory monitoring. This includes pediatric hematology and oncology patients. We report on the feasibility and successful implementation of a home phlebotomy program that has minimized disruption in care for this high-risk patient population. During the initial months of the COVID-19 outbreak, we completed 189 home phlebotomy visits for pediatric hematology and oncology patients. Patient and staff satisfaction with the program were high, and potential exposures to COVID were avoided.

Direct Oral Anticoagulants (DOACs) have shown to be at least effective and safer than anti-vitamin K (VKA) for the prophylaxis of cardioembolism during AF. These drugs do not need laboratory monitoring such as the VKA anticoagulants, but they are at risk of poor adherence and persistence as all drugs taken by mouth. Against this drawback, empathy may have an important role because it is important as a tool to be used for effective interpersonal communication. Patients like to be heard and understand that those who listen to them are immersed in their world. Empathy is part, and is a founding principle, of Narrative Medicine which today is a real discipline with many advantages because it is intrinsically therapeutic for the patient (in telling and being heard). Empathy prevents the disconnection that can intervene between the doctor and the patients. Have we ever wondered if we are sufficiently empathetic? Is it possible to measure our empathy? Yes, across Jefferson's scale. A high score on Jefferson's scale could certainly further improve the quality of the management of anticoagulated patients.

The classical oral anticoagulants are increasingly being replaced in clinical practice by new antithrombotic drugs, which act by enabling direct inhibition of coagulation factor IIa (FIIa) or factor Xa (FXa). These drugs have multiple acronyms, including NOACs (new, non–vitamin K antagonist) or DOACs (direct oral anticoagulants), and currently include dabigatran (FIIa inhibitor), and rivaroxaban, apixaban, and edoxaban (FXa inhibitors). These drugs are approved for stroke prevention in patients with non-valvular atrial fibrillation and the prevention and treatment of venous thromboembolism. The "mantra" that DOACs do not require laboratory monitoring is not entirely correct because laboratory testing for drug effects is needed in many situations, because they influence hemostasis tests and in situations in which urgent measurement of DOACs is required. This should be very important to consider in the clinical situation for numbers of indications and increasing numbers of patients on DOACs therapy. The main aim of this article is to provide practical issues to general laboratory testing for DOACs, as well as to help avoid diagnostic errors associated with hemostasis testing. The assays for DOAC quantification must be available in medical centers on a whole day basis, to facilitate optimal drug management in conditions when things go wrong or in urgent cases of immediate reversal of anticoagulation or appropriate administration of a specific antidote. Nova generacija oralnih antikoagulantnih lekova omogućava direktnu inhibiciju FIIa ili FXa, i sve više zamenjuje klasične antikoagulanse u kliničkoj praksi za različita stanja. Ovi lekovi su označeni sa nekoliko akronima, uključujući NOAC, DOAC, i odnose se na nove (ne-vitamin K antagoniste) i direktne oralne antikoagulanse, a trenutno uključuju dabigatran (FIIa inhibitor), i rivaroksaban, apiksaban i edoksaban (FXa inhibitori) . Direktni oralni antikoagulantni lekovi odobreni su za prevenciju moždanog udara kod pacijenata sa ne-valvularnom atrijalnom fibrilacijom i za prevenciju i lečenje venskog tromboembolizma. "Mantra" da direktni oralni antikoagulantni lekovi ne zahtevaju laboratorijsko praćenje ne može se prihvatiti u mnogim kliničkim situacijama. Štaviše, pošto ovi lekovi "ne zahtevaju" laboratorijsko praćenje, neki kliničari su to prihvatili kao da ne utiču na testove u hemostazi. Postoji više situacija u kojima je potrebno rutinsko i hitno određivanje DOAC-a, pri čemu će se broj laboratorijskih zahteva povećavati u budućnosti jer sve više zamenjuju konvencionalne antikoagulanse za sve veći broj indikacija, kod sve većeg broja pacijenata. Glavni cilj ovog rada je da odgovori na praktična pitanja u opštem laboratorijskom ispitivanju DOAC-a, kao i da pomogne u uklanjanju i smanjenju dijagnostičkih grešaka povezanih sa ispitivanjem hemostaze. Testovi za kvantifikaciju DOAC-a moraju biti dostupni u medicinskim centrima 24 sata, kako bi se olakšalo optimalno lečenje u uslovima kada stvari pođu po zlu ili u hitnim slučajevima trenutnog ukidanja antikoagulantne terapije ili odgovarajuće primene specifičnog antidota.

This article discusses the importance of eliciting the mechanisms of action and the metabolism of microbiota in the critically ill patients, as well as the role of nutrition specialist in the management of these patients.In critically ill patients the impaired regulation of endogenous metabolic processes and protein-energy deficiency are aggravated by abnormal microbiota metabolic processes. There is growing awareness of the importance of studying microbial metabolism in the general metabolic process. Its implications for the improved efficacy of treatment in critical care and rehabilitation are obvious.Current international intensive care guidelines are being constantly revised in response to the new research data available on the mechanisms of critical illness. The course of the latter may significantly associate with the metabolic activity of human microbiota. Active management of metabolic processes is being sought through the subordination of bacterial metabolism to the interests of the host. Both antimicrobial and bioformulations (prebiotics, metabiotics) will be used in the long term in a targeted manner with the control of key microbial metabolites through available laboratory monitoring tools.Based on the literature data and the original research, the author formulates postulates of the microbiota metabolism in critical illness, introduces the concepts of «invisible organ dysfunction» and «signaling bacterial molecules», offers answers to the eternal «what is to be done?» question and suggests using a number of microbial aromatic amino acids metabolites as an integral indicator of a course of critical illness.

INTRODUCTION The factor VIII mimetic emicizumab (Hemlibra, Hoffman-la Roche, Basel, Switzerland) has a novel mode of action that affects the laboratory monitoring of patients receiving this treatment. AIM This guideline from the United Kingdom Haemophilia Centre Doctors Organisation (UKHCDO) aims to provide advice for clinical and laboratory staff on appropriate use of laboratory assays in patients with Haemophilia A treated with emicizumab. METHODOLOGY The guideline was prepared by a review of the available literature and discussion and revision by the authors. RESULTS The guideline describes the effect of emicizumab on commonly used coagulations tests and provides recommendations on the use of assays for measurement of factor VIII and factor VIII inhibitor in the presence of emicizumab. The guideline also provides recommendations on measurement of emicizumab. CONCLUSION Knowledge of the effect of emicizumab on coagulation tests and factor assays is required to ensure appropriate testing and monitoring of therapy in patients receiving this drug.

Assay discrepancies can occur with laboratory monitoring of FVIII and FIX replacement therapy, particularly for the extended half-life products. This guideline collates current published data and provides advice on appropriate choice of assays for laboratory measurement of replacement therapy for patients with Haemophilia A and B without inhibitors. It is recommended that each haemophilia centre should ensure that appropriate laboratory assays are available for FVIII and FIX products in local clinical use. Patient samples should be assayed against calibrators traceable to WHO Plasma International Standards. Assay discrepancies are common especially for the extended half-life FVIII and FIX products, and assays of these products may need to be verified with the specific CFC being used.

Purpose The aim of this study is to understand the frequency of appropriate laboratory monitoring of oral chemotherapy at the Eastern Colorado Health Care System (ECHCS) compared to recommendations set forth in the 2012 Veterans Health Administration (VHA) Guidance on Dispensing and Monitoring of Oral Chemotherapy. Methods This study is a retrospective chart review of patients who have received a subset of oral chemotherapy drugs at ECHCS. Patients 18 to 89 years of age with an active cancer diagnosis who initiated therapy at ECHCS between September 1, 2010 and August 31, 2014 were included in the study. Initial and subsequent prescription fill dates, appropriate labs as defined by VHA guidance and baseline and follow-up lab monitoring dates, and appropriate labs as defined by VHA guidance were collected for up to 12 cycles of chemotherapy per patient. Baseline labs were defined as within three months of the first prescription fill date, and follow-up labs were defined as within seven days of subsequent prescription fill dates. Results Results are presented as complete, partial, or incomplete and as attempt or no attempt at monitoring according to the VHA guidance recommendations. There was 100% attempt at laboratory monitoring at baseline; however, there was a decline in attempt and complete follow-up monitoring overall as well as for drugs that require special monitoring. Conclusion Based on recommendations from the 2012 VHA Guidance on Dispensing and Monitoring Oral Chemotherapy, data presented here demonstrate that ECHCS could benefit from improved lab monitoring in order to ensure safe and effective use of oral chemotherapies. These results provide a unique opportunity to consider the potential role of clinical pharmacists in monitoring and management of patients receiving oral chemotherapies as well as patient and provider education regarding the importance of appropriate lab monitoring.

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations. All the organisations were in general agreement concerning the following key points: Only men meeting the criteria for testosterone deficiency (TD) should be treated. Consider screening asymptomatic men with certain conditions that increase the risk of TD. Exogenous TTh causes impairment of spermatogenesis. There is no evidence that TTh causes prostate cancer. Men on TTh require careful laboratory monitoring.

Safe prescribing for persons with severe mental illness requires laboratory monitoring for psychotropic drug levels and metabolic side effects. Barriers to appropriate and timely monitoring increase when clients must obtain phlebotomy services at a separate facility. This quality improvement project was conducted within a program for assertive community treatment (PACT). Specific aims were to increase access to laboratory testing, improve efficiency, and lower costs by implementing on-site specimen collection. Outcomes, measured three months post-implementation, indicate that over half of all labs were obtained on-site, clients and staff were pleased with increased efficiencies, and costs were reduced by 37%.

The effects of bone graft materials on the inflammatory response and biochemical markers of bone remodeling were studied on a rabbit model of fracture augmentation with the following grafts: β-tricalcium phosphate, demineralized bone matrix, nanostructured carbon implant, and porous titanium implant made by additive 3D printing. The markers of bone remodeling and the blood system response in the postoperative period were studied. It was found that porous titanium implant and β-tricalcium phosphate induced osteogenesis and minimized osteoclastic resorption. Augmentation with nanostructured carbon implant and demineralized bone matrix stimulated the processes of osteoclastic resorption.

Purpose The purpose of this project was to determine whether the use of the modified Northwestern high risk spine protocol in patients undergoing multilevel spinal fusion surgery would result in improved transfusion practices. Design Preimplementation and postimplementation design. Methods A laboratory monitoring and transfusion guideline protocol was implemented in patients undergoing multilevel spinal fusions. Data were collected via a manual retrospective chart review of the electronic medical record before and after implementation of the protocol. Findings Laboratory values were monitored at guided intervals. There was a statistically significant (P = .004) decrease in the mean hemoglobin value at which a packed red blood cell transfusion was initiated. Conclusions Through the use of the protocol, laboratory value monitoring provided quantitative data to aid and improve clinical decision making for practitioners in the perioperative period.

Background: Advances in multiple sclerosis (MS) disease modifying therapy (DMT) have increased laboratory monitoring requirements. Our goal was to survey existing practices and perceptions of risk in laboratory monitoring throughout Canada and assess whether opportunities to improve patient care and safety exist. Methods: A web-based survey assessing prescriber demographics, current infrastructure, and concerns for lab monitoring was sent to the Canadian Network of MS Clinics (CNMSC) listserv, inviting MS clinicians across the country to participate. Results: Respondents included 32/65 CNMSC-affiliated neurologists (49%), 6 registered nurses (RN), 2 nurse practitioners (NP), and 2 non-neurologist physicians from 8/10 provinces. For some questions, analysis was limited to 34 DMT-prescribing clinicians only. Despite broad implementation of electronic medical records (25/34, 74%), many prescribers (15/34, 44%) still receive laboratory results in paper form. In terms of lab monitoring infrastructure, we noted regional variability in the employment of nursing to monitor patient compliance with required laboratory monitoring. There is also a gap in laboratory surveillance, as less than 5% of respondents reported regularly reviewing results on weekends. Providers’ length of practice and volume of MS patients were not associated with different perception of DMT laboratory monitoring risk. Conclusions: This nation-wide survey showed variability in infrastructure used in laboratory monitoring and regional variation in nursing involvement. Providers’ level of concern for laboratory monitoring for DMTs did not vary by years of experience or volume of MS patients followed, suggesting that improved systems, rather than education, could ameliorate perceptions of risk.

The system of epidemiological surveillance of community-acquired pneumonia (VP) in the Russian Federation (RF) has changed since 2011. As a result, additional opportunities have emerged for a comparative analysis of the incidence of EP and ARVI. The goal is to give a comparative description of the incidence of CAP and ARVI by age groups, territories and seasonality, taking into account the results of a selective laboratory examination of patients.Materials and methods.A retrospective descriptive epidemiological study on the results of epidemiological surveillance at the regional level (Irkutsk Region, 2012–2016) was conducted. For 2016, the dynamics of the patient’s number with influenza and acute respiratory viral infections (n = 706460) and VP (n = 15279) reported by weeks, as well as the results of selective PCR examination of 1788 patients for 13 viral and bacterial pathogens were analyzed.Results.Over 5 years, the incidence of the VP increased from 377.6 (370.0–385.2) per 100 thousand to 588.3 (578.7–597.9), the average annual growth rate was + 35.8%. At the same time, the incidence of ARVI decreased at an average annual rate of –2.9%. When comparing the incidence of CAP and ARVI in municipalities, it was found weakly correlation only (ρ = 0.172, p> 0.05). In contrast, in the analysis of seasonality, a direct strong correlation was found between SARS and EP by weeks of the year (ρ = 0.887, p Conclusion.The introduction of the epidemiological monitoring system for pneumonia allowed to identify differences in the intra-annual dynamics of EF and ARVI among adults and children. This is the basis for correcting the tactics laboratory monitoring and prophylaxis of acute respiratory infections.

Home-based PrEP monitoring (HBPM) has the potential to improve PrEP access and retention but is hampered by difficulties collecting blood, which typically involves painful fingersticks that yield insufficient specimen for quantitative syphilis serologies. We evaluated the use of the Tasso OnDemand™, a device that facilitates relatively painless self-collection of enough blood for HIV, creatinine, and quantitative rapid plasma reagin testing. From May 2020 – January 2021, we recruited subjects for two studies of the Tasso device and HBPM preferences. First, we sent invitations to English-speaking clients enrolled in an online messaging platform and receiving PrEP through the Sexual Health Clinic (SHC) in Seattle, WA, asking them to view a Tasso device video and complete a survey. In a second study, we recruited SHC PrEP clients and persons with known/suspected syphilis or living with HIV. After brief instruction in clinic, clients used the Tasso device and completed a survey about their experience. Of 509 clients offered participation online and 46 in clinic, 102 (20%) and 46 (100%), respectively, completed surveys. Most participants were cisgender men (132, 90%) of median age 34 years who identified as non-Hispanic White (78, 52.7%). Thirty-seven (45%) reported a history of syphilis. Given current COVID restrictions, 124 (89.2%) participants were interested in self-collecting PrEP laboratory samples at home. Many felt home sampling kits would increase their likelihood of staying on PrEP (61/135, 45.2%). Of the 46 participants who self-collected blood specimens in clinic, 42 (93.3%) felt the process was easy and 35/36 (97.2%) PrEP-eligible participants felt they could similarly self-collect blood at home. Self-collection of blood specimens using the Tasso device is feasible and acceptable to persons using PrEP. Future studies will assess how often individuals will use this device rather than come to the SHC for PrEP care and the impact of HBPM on PrEP retention.

Oral dexamethasone mini pulse (OMP) is an established treatment modality for active vitiligo. Cyclosporine may have therapeutic role in active vitiligo but current evidence supporting its role is scarce. The objective of study was to compare the efficacy and safety of oral cyclosporine with OMP in patients of active vitiligo. Fifty patients with active vitiligo were randomized into two groups of 25 patients. Group 1 was treated with OMP (2.5 mg dexamethasone) on two consecutive days/week for 4 months while group 2 was treated with cyclosporine (3 mg/kg/day) for 4 months. Laboratory monitoring was performed as per the prevalent protocol. The patients were followed up for another 2 months after stopping treatment. Arrest of disease progression (ADP) was defined as change of vitiligo disease activity score from 4+ to 3+ (time elapsed since last disease activity being more than 6 weeks upto 3 months) during the study period (6 months). ADP was attained in 21 patients in group 1 and 22 patients in group 2 (84% vs. 88%, p = 1.00) at the end of 6 months. However, mean time to achieve ADP was significantly lower in group 2 as compared to group 1 (10.92 [4.12] weeks vs. 13.90 [3.92] weeks, p = 0.01). Extent of repigmentation, improvement in patient assessment score, vitiligo quality of life and clinical markers of disease activity were marginal and comparable in both groups. Cyclosporine leads to earlier disease stabilization in active vitiligo as compared to OMP. Although considered a rescue drug in dermatology, low dose cyclosporine can be an effective therapeutic alternative in vitiligo patients.

Background: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. Objective: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. Methods: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. Results: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). Conclusion: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration.

Background/objectives Literature regarding the cost and necessity of laboratory monitoring during oral antifungal treatment in adults has recently been published. However, consensus guidelines for the treatment and monitoring of pediatric patients with systemic antifungals for onychomycosis are lacking. We sought to evaluate both the practice trends and perspectives of pediatric dermatology providers who treat pediatric onychomycosis. Methods An electronic survey was administered to providers belonging to the Society for Pediatric Dermatology (SPD) and/or Pediatric Dermatology Research Alliance (PeDRA) regarding their clinical practice and reasoning for laboratory monitoring during the treatment of pediatric onychomycosis. Results One hundred and twenty-one providers completed the survey (12.5%). 77% identified themselves as pediatric dermatologists. A majority practice in the academic setting (51%), and 54% were primarily only pediatric providers. All respondents prescribe oral terbinafine for onychomycosis. 88% of respondents always or almost always confirm the diagnosis of onychomycosis prior to prescribing oral terbinafine for onychomycosis. 39% always or almost always routinely order baseline laboratory tests while 40% never or almost never do. 41% never or almost never order monitoring laboratory tests during treatment while 32% always or almost always do. 91.5% have never discovered a significant reaction to terbinafine with routine monitoring. Conclusion Pediatric dermatology providers are very likely to confirm the diagnosis of onychomycosis prior to systemic treatment. Significant variability was found in pretreatment and treatment laboratory monitoring, reasons for laboratory monitoring or deferral of testing, and timing of testing among providers. Knowledge of current practice trends as well as provider perspectives may be useful in the future development of consensus guidelines.

Gay, bisexual and other men who have sex with men (MSM) and transgender individuals face the highest burden of human immunodeficiency virus (HIV) infection. HIV pre-exposure prophylaxis (PrEP) is an effective evidence-based biomedical intervention to reduce acquisition of HIV infection but uptake has been suboptimal in lesbian, gay, bisexual, and transgender (LGBT) populations. Primary care providers play an integral role in addressing HIV disparities by educating patients and facilitating access to PrEP. After PrEP initiation, primary care providers should assess for and manage adverse effects, provide appropriate laboratory monitoring, support adherence, and assist patients with access to low-cost or free PrEP options if needed.

Purpose The aim of this review is to compare and contrast evidence-based clinical practice guidelines from global dermatological organizations for the use of ustekinumab in psoriasis. Materials and methods Clinical practice guidelines from the American Academy of Dermatology (AAD), National Psoriasis Foundation (NPF), British Association of Dermatologists (BAD), and European S3 were reviewed and compared. Results Practice guidelines from the three dermatological organizations are similar with regards to treatment dosage and initiation but differ in their recommendations for baseline screening and interval laboratory monitoring, treatment in patients undergoing surgery or receiving live vaccines, and treatment contraindications. Conclusion Ustekinumab is an effective and well-tolerated systemic treatment for patients with psoriasis and should be considered in the line of therapy that dermatologists discuss with their patients. Consideration should be given to evidence-based practice guidelines of global dermatology organizations to effectively guide treatment decisions in patients with psoriasis. This article is protected by copyright. All rights reserved.

Present treatment regimens for tuberculosis (TB) are long, complex, and, for drug-resistant TB, toxic and expensive. Priorities in designing new and improved regimens are to shorten and simplify treatment, decrease the incidence of side effects with minimal clinical or laboratory monitoring, ensure high-cure rates and affordability, linked with better point-of-care diagnostics. Markedly improved therapeutic regimens are dependent on having a robust pipeline of novel TB drug candidates. While the present pipeline is more robust than ever, it is still most likely insufficient to meet the goals of many of the present target regimen profiles, especially that of a pan-TB or universal regimen. Joint efforts are needed to identify novel drug combinations that would permit reaching the goals of shorter, better, and safer treatment. Faster and more efficient drug development pathways with novel designs will be extremely beneficial in reaching the goals of improved therapies.

A key limiting factor in the radiotherapy of liver malignancies is the relatively low tolerance of the liver parenchyma to radiation. This can lead to subclinical focal or generalized injury of the liver parenchyma under radiation treatment. It is of great importance to detect the rare complication of radiation-induced liver disease (RILD) early and to treat it symptomatically, as well as to protect patients with increased risk by preventive medication.

Objectives: The Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guidelines provide monitoring recommendations for children who are treated with second-generation antipsychotics (SGAs). The objective of this study was to determine the impact of the CAMESA guidelines on SGA monitoring in children with neurodevelopmental disorders. Methods: A retrospective chart review compared laboratory monitoring in children treated with SGAs who were referred to a tertiary psychopharmacology clinic before (2008–2011) and after (2013–2016) CAMESA publication. Chi-squared tests were used to detect changes in SGA use and monitoring between the two time periods. Results: A total of 345 charts were reviewed (n = 136 pre-CAMESA, n = 209 post-CAMESA). The proportion of children taking an SGA increased significantly (35% vs. 49%; p = 0.02) as did the duration of SGA treatment before tertiary assessment (18.6 months vs. 27.2 months; p = 0.03). SGA monitoring data were missing in 40% of charts pre-CAMESA and in 31% of charts post-CAMESA. The proportion of patients with any available laboratory monitoring did not change between the time periods (35% pre-CAMESA vs. 39% post-CAMESA; p = 0.56). Similarly, the proportion of patients with full laboratory monitoring was not significantly different between time periods (15% pre-CAMESA vs. 25% post-CAMESA; p = 0.23). Conclusions: SGA monitoring rates did not significantly improve after CAMESA guideline publication. To maximize benefit and mitigate risks of these medications, there is a need to identify barriers to SGA monitoring.

Introduction Dupilumab is a biologic therapy approved for treatment of moderate to severe atopic dermatitis (AD). Our objective was to assess the real-world effectiveness, safety and laboratory monitoring practices for dupilumab in a tertiary centre. Methods A retrospective review of medical records of all patients receiving dupilumab between September 2017 and October 2019 was undertaken. Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) were collected at weeks 0, 12–16 and 26–30. Data on laboratory tests undertaken for dupilumab screening and monitoring were also collected. Results At 12–16 weeks, 58.9% and 37.3% of patients achieved ≥ EASI 75 and ≥ EASI 90, respectively (n = 156). Ninety-four patients underwent further analysis at weeks 26–30 with those achieving ≥ EASI 75 increasing from 61.7% (12–16 weeks) to 75.31%, and EASI 90 increasing from 35.8% (12–16 weeks) to 49.8%. The most common side effects were eye symptoms occurring in 43.1% of patients, with 16.3% developing conjunctivitis. The mean treatment duration was 255 days, during which an average of three sets of blood tests were performed (n = 149). Of all laboratory abnormalities recorded, 24% started after initiation of dupilumab, and 93% were classified as ‘mild’. Dupilumab was not documented as causative in any of the cases, nor was treatment stopped on account of laboratory abnormalities. Conclusion Dupilumab provides an effective and safe treatment option for patients with AD. Clinical response continued to improve past 16 weeks in this real-world population. No laboratory abnormalities were felt to be secondary to dupilumab; screening and monitoring tests did not influence dupilumab prescribing. Electronic supplementary material The online version of this article (10.1007/s13555-020-00469-6) contains supplementary material, which is available to authorised users.

Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy. Some, such as hypoglycaemia or severe hyponatraemia, can be fatal without prompt identification and treatment. Failure to identify seizures associated with recreational drug or alcohol misuse can lead to inappropriate AED treatment, as well as a missed opportunity for more appropriate intervention. In individuals with established epilepsy on treatment, some laboratory monitoring is desirable at least occasionally, in particular, in relation to bone health, as well as in situations where changes in AED clearance or metabolism are likely (extremes of age, pregnancy, comorbid disorders of renal or hepatic function). For any clinician managing people with epilepsy, awareness of the commoner derangements associated with individual AEDs is essential to guide practice. In this article, we review indications for tests on blood, urine and/or cerebrospinal fluid in patients presenting with new-onset seizures and status epilepticus and in people with established epilepsy presenting acutely or as part of planned monitoring. Important, but rare, neurometabolic and genetic disorders associated with epilepsy are also mentioned.