Current Monitoring Guidelines Research Articles

JAK 1-3 inhibitors and TYK-2 inhibitors in dermatology: Practical pearls for the primary care physician

ABSTRACT Guidelines for primary care clinicians on monitoring and safety guidelines regarding Janus kinase and tyrosine kinase 2 inhibitors in the treatment of inflammatory skin conditions are often unclear. This review aims to provide the primary care physician with a review of clinically relevant and updated information regarding the monitoring and overall profile of these medications. To do so, a systematic review was conducted using the PubMed database and relevant Food and Drug Administration (FDA) approved drug inserts from manufacturers. Janus kinase and tyrosine kinase 2 inhibitors have recently gained FDA approval for the treatment of several inflammatory skin conditions including atopic dermatitis, plaque psoriasis, alopecia areata, and vitiligo. There is a known box warning associated with the Janus kinase inhibitors that create the need for monitoring and close follow-up while patients are undergoing these treatments. Although these medications are often prescribed by specialists, as their use becomes more prevalent and therapies continue to gain approval for the treatment of these commonly encountered conditions, it is important for the primary physician to be updated and aware of the current monitoring guidelines and safety profile for this class of medication. Both Janus kinase inhibitors and tyrosine kinase 2 inhibitors display significant efficacy in the treatment of their approved conditions and research continues to move forward with the approval of more medications from these classes.

Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated

The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9kPa (adjusted odds ratio= 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio= 1.76; 95% CI 1.20-2.56; p= 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.

Influence of non-invasive blood pressure measurement intervals on the occurrence of intra-operative hypotension.

The American Society of Anesthesiologists Standards for Basic Monitoring recommends blood pressure (BP) measurement every 5min. Research has shown distractions or technical factors can cause prolonged measurement intervals exceeding 5min. We investigated the relationship between prolonged non-invasive BP (NIBP) measurement interval and the incidence of hypotension, detected post-interval. Our secondary outcome was to determine independent predictors of these prolonged NIBP measurement intervals. Retrospective data were analyzed from 139,509 general anesthesia cases from our institution's Anesthesia Information Management System (AIMS). Absolute hypotension (AH) was defined a priori as a systolic BP < 80mmHg and relative hypotension (RH) was defined as a 40% decrease in systolic BP from the preoperative baseline. Odds ratios (OR) with 95% confidence intervals and Pearson's Chi square Test reported the association of prolonged NIBP measurement intervals on hypotension detected post-NIBP measurement interval. Logistic regression models were developed to determine independent predictors of NIBP measurement intervals. The analysis revealed that NIBP measurement intervals greater than 6 and 10min are associated with an approximately four times higher incidence of a patient transitioning into hypotension (AH/RH > 6min OR 4.0 / 3.6; AH/RH > 10min OR 4.3 / 3.9; p < 0.001). A key finding was that the "> 10-minute AH model" indicated that age 41-80, increased co-morbidity profile, obesity and turning (repositioning) of the operative room table were significant predictors of prolonged NIBP measurement intervals (p < 0.001). While we do not suggest NIBP measurement intervals cause hypotension, intervals greater than 6 and 10min are associated with a fourfold increase in the propensity of an undetected transition into both RH or AH. These data support current monitoring guidelines.

Spatio-temporal distribution patterns of three stream-dwelling freshwater mussel species: towards a strategy for representative surveys

Conservation efforts for freshwater mussels (Unionoida) require a priori assessments of their populations’ status quo. Unfortunately, collection of representative census and other data for most European species is currently hampered by an insufficient understanding of inter- and intra-specific variation in distribution patterns. We assessed distribution and movement in three Unio crassus populations and one sympatric population of Anodonta anatina and Unio pictorum, respectively. We surveyed vertical movement across four sediment depths, and horizontal movement by mark-recapture technique in 3-month intervals. For all the populations, movement and the proportion inhabiting surface layers increased considerably from winter to spring/summer. Spatial aggregation levels remained stable for some populations, while others became increasingly randomly distributed during the study. One U. crassus population exhibited elevated mortality and displayed movement rates exceeding twice those of conspecific populations. The visible proportion of U. crassus populations differed by up to 69% between sites. Current monitoring guidelines in Europe often insufficiently account for the extensive inter- and intra-specific differences in spatio-temporal distribution patterns observed. We suggest developing internationally standardised protocols that specify sampling season and methodology. In particular, U. crassus surveys should be restricted to summer months, and hand-sampling is crucial for some populations.

Patterns of relapse and progression in multiple myeloma patients after auto-SCT: implications for patients’ monitoring after transplantation

Auto-SCT (ASCT) is widely used in first-line treatment of multiple myeloma (MM). However, most patients eventually relapse or have progression of disease (R/POD). Although precise knowledge of R/POD patterns would be important to generate evidence-based surveillance recommendations after ASCT, such data is limited in the literature, especially after introduction of the free light chain assay (FLCA). This retrospective study examined the patterns of R/POD after first-line ASCT in 273 patients, using established criteria. At the time of R/POD, only 2% of patients had no associated serological evidence of R/POD. A total of 85% had asymptomatic R/POD, first detected by serological testing, whereas 15% had symptomatic R/POD with aggressive disease, early R/POD and short survival, with poor cytogenetics and younger age identified as risk factors. Although occult skeletal lesions were found in 40% of asymptomatic patients tested following serological R/POD, yearly skeletal surveys and urine testing were poor at heralding R/POD. We found a consistent association between paraprotein types at diagnosis and R/POD, allowing informed recommendations for appropriate serological monitoring and propose a new needed criterion using FLCA for patients relapsing by FLC only. Our findings provide important evidence-based recommendations that strengthen current monitoring guidelines after first-line ASCT in MM.

Surveying for biotic soil crust lichens of shrub steppe habitats in the Columbia Basin.

Arid lands of eastern Oregon and Washington support a great diversity of biotic soil crust organisms that are often overlooked in biotic inventories. Land managers are increasingly interested in incorporating these species in their surveys so that they can protect unique habitats and prevent uncommon species from becoming threatened. Current monitoring guidelines for rangeland health sometimes take into account the percent cover by soil crusts; however, there is very little guidance for surveying for uncommon species. Furthermore, because soil crust species and habitats are unfamiliar to most botanists, finding these species presents special challenges. We outline suggestions for future surveys with these goals.

Clinical Monitoring Guidelines for Congenital Hypothyroidism: Laboratory Outcome Data in the First Year of Life

To examine whether current recommendations for thyroid status monitoring in children with congenital hypothyroidism (CH) (monthly in the first 6 months and every 3-4 months subsequently) are adequate, or whether monthly monitoring is necessary throughout the first year. We reviewed charts of 70 children with CH for initial thyroid-stimulating hormone (TSH), frequency of follow-up, dose changes, and thyroxine (T(4)) and TSH levels in the first year. Need for monthly monitoring was determined on the basis of guidelines to maintain T(4)/free T(4) in the upper half of the normal range and rapidly normalize TSH. Monthly monitoring was justified in 75% in the first 6 months and 36% in the next 6 months. Children requiring monthly monitoring in the second 6 months had higher baseline TSH (P = .02) and lower T(4) (P = .01) than those not requiring monthly monitoring. Thyroid dysgenesis, starting levothyroxine dose, sex, and ethnicity did not predict requirement for monthly monitoring. Thirty percent of children in the first and second 6 months had ≥1 high TSH level, with a T(4)/free T(4) not in the upper half of the normal range. More than a third of children with CH require monthly monitoring between 6 to 12 months on the basis of study criteria. Current monitoring guidelines may need to be reexamined.

Pediatric Endocrinologists' Management of Children With Type 2 Diabetes

OBJECTIVETo understand physician behaviors and attitudes in managing children with type 2 diabetes.RESEARCH DESIGN AND METHODSA survey was mailed to a nationwide sample of pediatric endocrinologists (PEs).RESULTSA total of 40% of PEs surveyed responded (211 of 527). Concordance with current monitoring guidelines varied widely, ranging from 36% (foot care) to 93% (blood pressure monitoring). Given clinical vignettes addressing hyperlipidemia, hypertension, and microalbuminuria, only 34% of PEs were fully concordant with current treatment guidelines. Reported barriers included concerns about patient adherence, insufficient scientific evidence about treatment, and lack of familiarity with current recommendations. Providers aged ≤45 years or in clinical practice <10 years reported significantly more aggressive management behaviors and had higher concordance with guidelines.CONCLUSIONSScreening and management of pediatric type 2 diabetes varied widely among PEs, suggesting opportunities for quality improvement. More aggressive management of type 2 diabetes among younger providers may be related to recent training when type 2 diabetes was more common.

Methotrexate: long‐term safety and efficacy in an Australian consultant rheumatology practice

The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment. A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX. Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42-0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier. MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.

Monitoring by rheumatologists for methotrexate-, etanercept-, infliximab-, and anakinra-associated adverse events.

To determine what monitoring protocols rheumatologists use to identify adverse events in rheumatoid arthritis (RA) patients treated with methotrexate (methotrexate), etanercept (etanercept), infliximab (infliximab), and anakinra (anakinra), how often rheumatologists encounter treatment-altering adverse events in their RA patients receiving these treatments, and how they feel about and comply with the current monitoring guidelines. Three hundred ten physician members of the American College of Rheumatology (ACR) were notified by e-mail of a survey that was posted on our rheumatology Web site. Questions were closed-ended and multiple choice in format. One hundred twenty-three responses were received (40%). Most rheumatologists reported that they utilize the ACR recommended screening tests at baseline before methotrexate treatment is initiated. Seventy-nine percent reported that treatment-altering abnormalities had occurred in <5% of their methotrexate-treated RA patients, and 88% reported that such abnormalities had occurred in <10% of such patients, in the previous 3 years. Forty-one percent believed liver function monitoring guidelines need to be changed; 59% said they would agree with new guidelines that would include a recommendation for liver function monitoring every 3-4 months. Most rheumatologists were not aware of any guidelines for monitoring by blood tests in RA patients treated with biologic agents, yet the majority reported that they order blood tests before patients start these therapies and on followup. Our survey indicates that treatment-altering liver function abnormalities in methotrexate-treated RA patients are rare, and more than half of rheumatologists agree that a less stringent monitoring regimen should be considered. Rheumatologists and pharmaceutical companies might work together to develop guidelines for monitoring of patients treated with biologic agents.