Therapy In Management Of Patients Research Articles

Impact of EUCAST rapid antimicrobial susceptibility testing (RAST) on management of Gram-negative bloodstream infection

ObjectivesDuring bloodstream infections, reducing the time to antimicrobial susceptibility testing is crucial to initiation of early appropriate antibiotic therapy. For Gram-negative infections, a phenotypic approach remains necessary. Rapid antimicrobial testing (RAST) is a recently developed phenotypic EUCAST method. The goal of this study was to evaluate the accuracy and clinical impact of RAST. Patients and methodsFrom September 2020 to August 2021, Gram-negative episodes with positive blood culture detected in the morning were included in the RAST group. Categorical agreement of RAST with conventional antimicrobial testing on strains was determined. To assess antibiotic management and patient outcomes, the RAST group was compared with a control group (CG) with positive blood culture detected in the afternoon for which overnight antimicrobial testing was performed. ResultsThe RAST group included 61 episodes from 61 patients, while the CG group included 49 episodes from 48 patients. While RAST performed on 41 E. coli, 11 K. pneumoniae and 9 P. aeruginosa strains highlighted 99.3 % of categorical agreement, 7.4 % of unreadable zones and 9.4 % of technical uncertainty area at 4 h incubation were also reported.For the RAST group, effective antibiotic therapy was prescribed in 100 % of patients on the day of positive blood culture (day 1) vs 88 % in CG (p = 0,007). As for beta-lactams on day 1, RAST led to 9 escalations and 6 de-escalations. Mortality and length of hospital stay did not significantly differ between the two groups. ConclusionRAST improves management of antibiotic therapy in patients with Gram-negative sepsis.

Timely Genetic Testing and Therapy Management in Patients With gBRCA-Mutated Metastatic Breast Cancer Receiving Talazoparib.

Talazoparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that has demonstrated strong efficacy with manageable side effects for patients with germline breast cancer susceptibility genes 1 or 2 (gBRCA1/2)- mutated, human epidermal growth factor receptor 2–negative, locally advanced or metastatic breast cancer (mBC) in the EMBRACA and ABRAZO trials. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer recommend genetic testing for all patients with recurrent or metastatic BC to identify those with a gBRCA1/2 mutation who would benefit from treatment with a PARP inhibitor. However, many patients who meet these criteria do not receive genetic testing for a variety of reasons. Advanced practitioners (APs) can play a key role in the care of these patients by guiding them through the genetic testing process and explaining how the results impact treatment choices. A hypothetical case study highlighting a 42-year-old woman who received a diagnosis of triple-negative mBC provides an example of genetic testing strategies, as well as management considerations, with the use of talazoparib that can be implemented by APs. The efficacy and safety of talazoparib are reviewed along with practical guidance on its use (i.e., managing adverse events and drug interactions) to optimize patient outcomes. The patient case described in this publication is fictional and does not represent actual events or a response from an actual patient. The authors developed this fictional case for educational purposes only.

Consensus Document on Perioperative Antithrombotic Management: Part 2. Case Study

Given the progressive improvements in antithrombotic strategies, management of cardiovascular disease has become sophisticated/refined. However, the optimal perioperative management of antithrombotic therapy in patients with acute coronary syndrome or who are scheduled for percutaneous coronary intervention remains unclear. Assessments of the thrombotic and hemorrhagic risks are essential to reduce the rates of mortality and major cardiac events. However, the existing guidelines do not mention these topics. This case-based consensus document deals with common clinical scenarios and offers evidence-based guidelines for individualized perioperative management of antithrombotic therapy in the real world.

PRINciples of optimal antithrombotiC therapy and coagulation managEment during elective fenestrated and branched EndovaScular aortic repairS (PRINCE2SS): An International Expert Based Delphi Consensus Study

Management of antithrombotic therapy in patients undergoing elective fenestrated branched endovascular aortic repair (F-BEVAR) is not standardised, nor are there any recommendations from current guidelines. By designing an international expert based Delphi consensus, the study aimed to create recommendations on the pre-, intra-, and post-operative management of antithrombotic therapy in patients scheduled for elective F-BEVAR in high volume centres.

Effect of treatment regimens in severe COVID pneumonia at an Indian tertiary care hospital: An observational, real-world study

BackgroundCorticosteroids have attracted attention as a treatment option for severe Coronavirus disease (COVID-19). However, published data on steroid therapy is debatable, and real-world data is lacking. This study evaluated the effect of treatment regimens, especially Pulse steroid therapy (Injection Methyl Prednisolone 250 mg iv once a day for three days) in severe-COVID-19 pneumonia at an Indian tertiary care hospital. MethodsThis observational cross-sectional study included severe COVID-19 pneumonia patients aged >18 years, requiring assisted ventilation. As part of the hospital protocol, patients received either pulse steroid therapy, remdesivir or tocilizumab in addition to the recommended steroid doses i.e., injection of dexamethasone 6 mg iv once a day. The association of factors and treatment regimens to patient outcomes was evaluated. ResultsData of eighty-three patients were assessed, majority being above 60 years (n = 30, 36.14%) and males (n = 45/83, 54.21%). The commonest comorbidities were hypertension (n = 26), diabetes (n = 23) and obesity (n = 19), fifty-five patients (66.26%) reported at least one comorbidity. Sixty-one patients (73.49%) had received pulse steroid regimen, forty-eight patients (57.83%) were administered remdesivir-based regimen while twelve patients (14.46%) had received tocilizumab treatment. 54.1% patients managed with pulse steroid regimens were discharged after treatment, statistically similar to remdesivir-managed subgroup (62.5%, p > 0.05). On sub-group analysis, pulse steroids showed better outcomes in young males with no comorbidities. No comorbidity had significant relationship with patient outcomes (p > 0.05). ConclusionPulse steroid therapy is an effective therapy in management of patients with severe COVID-19 pneumonia in a real-world setting, with better outcomes in young males without comorbidities. Pulse steroids can be considered a viable option for severe-COVID-19 pneumonia management.

Pharmacist-led medication reconciliation on admission to an acute psychiatric hospital unit.

Background:Therapy management in patients suffering from mental health disorders is complex and the risks derived from changes or interruptions of treatment should not be ignored. Medication reconciliation in psychiatry may reduce medication errors and promote patient safety during transitions of care.Objective:To identify the influence of complementary information sources in the construction of the best possible medication history, and to ascertain the potential clinical impact of discrepancies identified in a medication reconciliation service.Methods:An observational study was conducted in an acute mental hospital unit, with a further validation in an internal medicine unit. Adult patients taking at least one medicine admitted in the unit were included. Patients/caregivers were interviewed upon admission and the information gathered was compared with hospital medical and shared electronic medical records. Once the best possible medication history was gathered, therapeutic information was reconciled against the prescription on admission to identify discrepancies. Potential clinical impact of medication errors was classified using the International Safety Classification.Results:During the study period, 148 patients were admitted, 50.7% females, mean age 54.6 years (SD=16.3). Collaboration of a caregiver was a needed in 74% of the interviews. In total, 1,147 drugs were considered to obtain patients’ best possible medication history. After reconciliation, 560 clinically sound intentional discrepancies were identified and 359 discrepancies required further clarification from prescribers: 84.12% “drug omission”, 5.57% “drug substitution”, 6.96% “dose change”, and 3.34% “dosage frequency change”. Potential clinical impact of these medication discrepancies was classified as: 95 mild, 100 moderate, and 29 severe medication errors.Conclusion:About 1 in three intentional discrepancies observed in a pharmacists-led medication reconciliation service required further clarification from prescribers, being 80% of them unintentional discrepancies. Results highlight the importance of the caregiver as source of information for the psychiatric patient, the relevance of analyzing shared electronic health records until 6 months before, and the need to use hospital medical records efficiently. Additionally, 29 discrepancies were classified as errors with potentially severe clinical impact. A medication reconciliation service is concluded to be feasible and necessary in a mental health unit.

중풍 후 경직완화를 위한 추나요법 제언

Objectives : This study aimed to the application of Chuna manual therapy in patients with stroke where much evidence is not available. Methods : Domestic databases (KOREANTK, OASIS, RISS, KISS, and KMBASE) were queried for literature showing application of Chuna manual therapy in stroke patients. Additionally, insufficient evidence was supplemented with expert consensus using the Delphi method. Based on the literature review and expert consensus, the aca- demic committee of the Korean Society of Chuna Manual Medicine reviewed and summarized the Chuna technique recommendations that can be applied to stroke patients. Results : There were six studies on Chuna manual therapy in stroke patients, and Chuna therapy was applied for pelvic, shoulder, and elbow joint spasticity. The expert Delphi survey did not agree with the application of the nine of the 69 standard Chuna techniques and deliberated on matters to be considered when applying Chuna man- ual therapy to stroke patients. Finally, based on clinical research literature and expert opinions, Chuna technique was recommended for patients with post-stroke spasticity. Conclusions : The application of Chuna therapy to non-muscular skeletal disorders, including stroke is recommended and should be applied while taking the necessary precautions.

뚜렛 장애에 대한 추나요법의 효과

Objectives : To assess the effectiveness of Chuna manual therapy in patients with Tourette's syndrome.
 Methods : We queried nine electronic databases using the keywords “Tourette's Syndrome” and “tuina OR chuna” to identify RCTs that investigated the effectiveness of Chuna manual therapy in patients with Tourette's syndrome.
 Results : Thirteen RCTs were selected according to the inclusion criteria. A system- atic review showed that Chuna manual therapy can have a curative effect on patients with Tourette's syndrome.
 Conclusions : In this study, 13 RCTs reported that Chuna manual therapy was effec- tive for Tourette's syndrome. These findings provide a basis for its clinical use. However, all studies involved populations belonging to the same country. Many stud- ies lacked details of the research methodology. Therefore, further studies are re- quired to produce high-quality evidence.

Alteration of Inflammatory Parameters and Psychological Post-Traumatic Syndrome in Long-COVID Patients.

The aim of our study is to evaluate the correlation between the psychological status of patients recovered from SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (long-COVID patients) and their inflammatory status. Three months after hospital discharge, ninety-three patients were recruited and categorized into two distinct populations: control and long-COVID (COrona VIrus Disease) group. Patients belonging to the control group presented with an entering diagnosis of cardiovascular, metabolic, or respiratory disease and a negative history of SARS-CoV-2 infection, whereas the long-COVID population presented with a severe SARS-CoV-2 infection treated in the sub-intensive Care Unit. Psychological evaluation was performed through the administration of the Symptom Checklist-90 (SCL90) and LDH (Lactate dehydrogenase), ferritin, CRPhs (C-high sensitivity Reactive Protein), NLR (Neutrophil-to-lymphocyte ratio), PLR (Platelet-to-lymphocyte ratio), and SII (systemic immune-inflammation index) were investigated. We highlighted that beyond the first three months after contagion, patients recovered from SARS-CoV-2 infection are characterized by the persistence of a systemic inflammatory state and are at high risk for developing somatization, depression, anxiety, and sleep disturbances. Interestingly, ferritin value was strongly correlated with sleep disorders (p < 0.05). Our study emphasizes how COVID-19 strategies for risk stratification, prognosis, and therapy management of patients should be implemented with a psychological follow-up.

The effect of a series of online CME activities on the multidisciplinary management of patients with GEP-NETs.

e23004 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, heterogenous neoplasms characterized by a wide spectrum of clinical manifestations. Management strategies are varied and include surgery, radiological intervention, cytotoxic chemotherapies, somatostatin analogs, TKIs, and novel peptide receptor radionuclide therapy (PRRT). Due to their clinical complexity, the diagnosis and treatment of GEP-NETS should involve collaboration between specialists in multiple disciplines. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists, gastroenterologists, and pathologists with respect to the use of novel systemic therapies for the multidisciplinary management of patients with GEP-NETs. Methods: The educational series consisted of 3 online, CME-certified activities. Educational impact was assessed with repeated pre-/post-education including multiple choice knowledge/competence questions and 5-point Likert scale confidence questions. Data from all oncologists, gastroenterologists, and pathologists who completed pre- and/or post-education assessments were aggregated across activities and stratified by learning theme. Relative changes in percentage of correct responses and clinicians who were confident (value of 4 or 5) were used to measure improvement in knowledge, competence, and confidence. A McNemar’s test assessed significant levels of changes reported with P values &lt; .05 considered statistically significant. The first activity in the series launched December 2020 and the last launched February 2021; data were collected until February 2022. Results: The educational series resulted in overall statistically significant improvements in oncologists’, gastroenterologists’, and pathologists’ knowledge, competence, and confidence after education (N = 125 to 455, P &lt; .05). Conclusions: This analysis demonstrates that oncologists’, gastroenterologists’, and pathologists’ knowledge, competence, and confidence regarding the use of novel systemic therapies in the multidisciplinary management of patients with GEP-NETs improved after education. Despite these improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in this clinical setting.[Table: see text]

Development of a Consensus-Based Cross-Domain Protocol for the Management of Elastic Compression Stocking Therapy in Patients With Deep Venous Thrombosis and Chronic Venous Disease: A Modified Delphi Study.

ObjectiveElastic compression stocking (ECS) therapy is commonly used in patients with deep venous thrombosis (DVT) and chronic venous disease (CVD). The provision of ECS therapy is complex, and studies indicate a lack of practical guidance and suboptimal collaboration among health care professionals. We aimed to reach consensus on critical issues of ECS therapy among the involved health care professionals and patients.MethodsA three-round modified Delphi analysis was performed in the Netherlands in which 56 health care professionals (internists, dermatologists, general practitioners, emergency room nurses, home care nurses, medical stocking suppliers, and occupational therapists) and seven patients were invited. The 21 statements included in this analysis were based on information collected from a previously conducted Functional Resonance Analysis Method and Realist Evaluation. We used 7-point Likert scale questions and a 75% threshold for consensus.ResultsOf the 63 persons invited for this study, 59 (94%) agreed to participate and responded in the first questionnaire round; of whom 52 were health care professionals and seven were patients (five DVT and two CVD). The overall response rate for the three questionnaire rounds was 91%. After completion of the rounds, full consensus was achieved on 19 out of 21 statements. No consensus was reached on the need for a follow-up appointment for CVD patients and who should be responsible to determine the ECS type (custom-made or standard).ConclusionWe identified 19 consensus-driven recommendations on treatment decisions and collaboration in ECS therapy among an interdisciplinary panel of health care professionals and patients. These recommendations form a basis for consensus-driven optimization of ECS therapy and should ideally be incorporated in a general cross-domain protocol for ECS therapy in patients with DVT and CVD.

Efficiency of manual therapy methods in treatment of patients with chronic tension type headache

BACKGROUND. The treatment of chronic tension headache mainly includes pharmacological methods, but the frequent side effects of medications and the presence of contraindications in some categories of patients determine the relevance of the search for alternative methods. One of them is the use of soft techniques of manual therapy with an impact on the myofascial structures of the head and cervical spine.&#x0D; AIM. To determine the effectiveness of manual therapeutic use in patients with chronic tension headache.&#x0D; MATERIAL AND METHODS. The clinical study was conducted in the period from 2019 to 2021. The study involved 49 patients with chronic tension headache, who were divided into 2 groups: the main (37 participants) and control (12 participants). In the main group, patients received 3 manual therapy sessions. In the control group, patients received drug therapy. After 1month and 6 months, the intensity, frequency of headache, the amount of drugs taken, and the effect of headache on work ability were assessed. Statistical processing was performed using the IBM SPSS software. The Friedman test and the Kendall coefficient of concordance were used; the Wilcoxon test and signs were used for the significance of the shift. The results of the data were taken as significant at p 0.05.&#x0D; RESULTS. After the therapy in the main group of strong intensity headaches decreased 6 times (p 0.05). The number of patients with an insignificant effect of headache on work ability increased 2 times (p 0.05), there were patients (21.6%) whose headache did not influence with their ability to work, while the differences were significant (p 0.05).There was a decrease in the frequency of headache attacks in more than half of the patients (62%) and for 4 times decrease of the number of painkillers (p 0.01). There were no significant changes in the incidence and intensity of headache in the control group.&#x0D; CONCLUSION. The use of manual therapy in patients with chronic tension headache reduces the frequency, intensity of headache, the amount of drugs used and the negative effect of headache on working capacity.

Effectiveness of 12-week inspiratory muscle training with manual therapy in patients with COPD: A randomized controlled study.

The benefits of inspiratory muscle training (IMT) in patients with COPD were reported. However, its effects are limited in severe COPD patients. Further researches are required in new and complementary modalities demonstrating IMT efficacy in severe COPD patients. This study aims to investigate effects of manual therapy (MT) additional over IMT on functional capacity, respiratory muscle strength, pulmonary function, dyspnea, fatigue, and quality of life in severe COPD patients. Sixty patients with COPD in GOLD stage III–IV were included in this prospective single‐blind randomized trial. Patients were randomly assigned to receive either MT additional over IMT at 40% of maximal inspiratory pressure (MIP) (n = 30) or only IMT (n = 30) for 12 weeks. MT group received MT during 12 weeks for 30 min additional to IMT. Pulmonary function, respiratory muscle strength, functional capacity, dyspnea, fatigue, and quality of life were evaluated by spirometry, mouth pressure device, six‐minute walk test, Modified Medical Research Council (mMRC) dyspnea scale, fatigue severity scale, and St. George's Respiratory Questionnaire (SGRQ), respectively. MT group had significantly greater improvement in FEV1%, FVC%, PEF%, respiratory muscle strength, function, dyspnea, fatigue, and quality of life compared with IMT group (p < 0.05). 6MWT (p < 0.001, effect size Cohen's d: 0.915), MIP (p < 0.001, effect size Cohen's d: 1.235), and mMRC score (p < 0.001, effect size Cohen's d: 0.982) were significantly improved in IMT with MT group. This study demonstrated that subjects in IMT with MT group had improved outcomes in functional capacity, respiratory muscle strength, pulmonary function, dyspnea, fatigue perception, and quality of life compared with alone IMT group.

Manual Therapy for Patients With Radiation-Associated Trismus After Head and Neck Cancer

Trismus is highly prevalent in head and neck cancer (HNC) survivorship. Current standards for trismus treatment include various stretch-based exercise protocols as a primary and single treatment modality with limited evidence regarding the role of manual therapy (MT) for this indication. To assess the effect size and associations of response to MT to increase oral opening in the setting of radiation-associated trismus. This retrospective case series was conducted at the University of Texas MD Anderson Cancer Center between 2016 and March 2020 (before COVID-19 interruption) and included 49 disease-free survivors of HNC who were referred for treatment of radiation-associated trismus. Intraoral MT (including or excluding external head and neck) targeting the muscles of mastication. Maximum interincisal opening (MIO) before and after the initial MT session compared with serial MT sessions. Covariates were examined to determine the association with response to MT for trismus. A total of 49 survivors of HNC (13 women [27%]; 24 [49%] 64 years or younger; 25 [51%] 65 years or older; mean [range] of 6.6 [0-33] years postradiotherapy were included, 9 [18.4%] of whom underwent a single MT session; 40 [81.6%] who underwent multiple sessions [mean, 6; median (range), 3 (2-48)]). The MIO improved after a single session by a mean (SD) of 4.1 (1.9) mm (0.45 effect size) and after serial MT sessions by a mean (SD) of 6.4 (4.8) mm with an effect size of 0.7. No covariates were found to be clinically meaningfully associated with MIO improvement following MT. The findings of this case series study suggest that MT improved MIO with a medium to large effect size in survivors of HNC with radiation-associated trismus. The results suggest that the largest increase in oral opening was achieved after the initial treatment and although gains were more modest, oral opening continued to improve with serial treatment. Covariates were not associated with MT response, suggesting that patients with clinical features often considered treatment refractory (eg, advanced disease, multiple lines of oncology treatment, ≥5 years posttreatment) may benefit from treatment with MT. Manual therapy may be a beneficial frontline or adjuvant treatment when combined with traditional stretching therapy. A clinically meaningful increase in oral opening has the potential to improve swallow function, speech, pain, and quality of life.

Editor's Choice – PRINciples of optimal antithrombotiC therapy and coagulation managEment during elective fenestrated and branched EndovaScular aortic repairS (PRINCE2SS): An International Expert Based Delphi Consensus Study

Management of antithrombotic therapy in patients undergoing elective fenestrated branched endovascular aortic repair (F-BEVAR) is not standardised, nor are there any recommendations from current guidelines. By designing an international expert based Delphi consensus, the study aimed to create recommendations on the pre-, intra-, and post-operative management of antithrombotic therapy in patients scheduled for elective F-BEVAR in high volume centres. Eight facilitators created appropriate statements regarding the study topic that were voted on, using a four point Likert scale, by a selected panel of international experts using a three round modified Delphi consensus process. Based on the experts' responses, only those statements reaching Grade A (full agreement ≥ 75%) or B (overall agreement ≥ 80% and full disagreement < 5%) were included in the final document. The round answers' consistency was graded using Cohen's k, the intraclass correlation coefficient, and, in case of double re-submission, the Fleiss k. Sixty-seven experts were included in the final analysis and voted the initial 43 statements related to pre- (n= 15), intra- (n= 10), and post-operative (n= 18) management of antithrombotic drugs. At the end of the process, six statements (13%) were rejected, 20 statements (44%) received a Grade B consensus, and 18 statements (40%) reached a Grade A consensus. Most statements (27; 71%) exhibited very high or high consistency grades, and 11 (29%) a fair or poor grading. The intra-operative statements mostly concentrated on threshold for and monitoring of proper heparinisation. The pre- and post-operative statements mainly focused on indications for dual antiplatelet therapy and its management, considering the possible need for cerebrospinal fluid drainage. Based on the elevated strength and high consistency of this international expert based Delphi consensus, most of the statements might guide current clinical management of antithrombotic therapy for elective F-BEVAR. Future studies are needed to clarify the debated issues.

Manual therapy interventions in the management of adults with prior cervical spine surgery for degenerative conditions: a scoping review

ObjectiveCervical spine surgeries for degenerative conditions are rapidly increasing. Cervical post-surgery syndrome consisting of chronic pain, adjacent segment disease, recurrent disc herniation, facet joint pain, and/or epidural scarring is common. Repeat surgery is regularly recommended, though patients are often unable to undergo or decline further surgery. Manual therapy is included in clinical practice guidelines for neck pain and related disorders, however clinical guidance for utilization of manual therapy in adults with prior cervical spine surgery is lacking. This study aimed to synthesize available literature and characterize outcomes and adverse events for manual therapy interventions in adults with prior cervical spine surgery due to degenerative conditions.MethodsPreferred reporting items for systematic reviews and meta-analyses extension for scoping reviews was followed. PubMed, Cumulative Index of Nursing and Allied Health Literature, physiotherapy evidence database, and Index to Chiropractic Literature were searched from inception through October 2021. English-language literature comprised of randomized clinical trials (RCT), case–control, cohort, and case report designs were included. Adults undergoing manual therapy, with or without combination of other interventions, with prior cervical spine surgery due to degenerative conditions were included.ResultsTwelve articles were identified, including 10 case reports, 1 low-quality RCT, and 1 acceptable-quality RCT. Eight case reports described 9 patients with history of fusion surgery. Two case reports described 2 patients with history of discectomy. One case report described one patient with separate operations of a discectomy at one level and a fusion at another level. One case report described 2 patients with history of cervical disc replacement surgery. The two RCTs included 63 and 86 participants, respectively. Use of manual joint mobilization/manipulation, table/instrument assisted mobilization/manipulation, and multimodal interventions were described in eligible studies. Favorable clinical outcomes were reported in 10 studies. Six case reports/series involving 8 patients described use of unclassified forms of manual therapy. Eight studies described the use of multimodal interventions along with manual therapy. One study described high patient satisfaction. Two studies, accounting for 3 patients, reported serious adverse events.ConclusionsThere is a lack of literature informing evidence related to clinical outcomes, patient satisfaction, and adverse events associated with manual therapy for patients with prior cervical spine surgery due to degenerative conditions. High-quality studies of higher-level hierarchical study design are needed to understand the clinical utility and safety profile of manual therapy for this population.

A150 ASSOCIATION BETWEEN SERUM USTEKINUMAB CONCENTRATIONS AND ENDOSCOPIC DISEASE ACTIVITY IN CROHN’S DISEASE

BackgroundTherapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown.AimsThe primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR).MethodsAdult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2018 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis.Results53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively).ConclusionsThere was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings.Funding AgenciesNone

Effects of glucosamine and chondroitin sulfate supplementation in addition to resistance exercise training and manual therapy in patients with knee osteoarthritis: A randomized controlled trial.

To determine the added benefits of short-term glucosamine and chondroitin sulfate supplementation in combination with manual therapy and resistance exercise training in the management of knee osteoarthritis. A parallel-design, double-blind randomised controlled trial was conducted from January to September 2020 at the Foundation University Institute of Rehabilitation Sciences and Fauji Foundation Hospital, Rawalpindi, Pakistan, and comprised of knee osteoarthritis patients of either gender having radiological evidence of grade III or less on Kellgren classification. The subjects were randomly allocated to active comparator group A and experimental group B. Both the groups received manual therapy and resistance exercise training, while group B additionally received glucosamine and chondroitin sulfate supplementation for 4 weeks. Study outcomes included pain, function, quality of life, range of motion, strength, fall risk, skeletal muscle mass, visceral fat area, body fat, intracellular water ratio, and segmental lean and fat mass. Data was analysed using SPSS 21. Of the 24 subjects, there were 12(50%) in each of the two groups. Each groups had 9(75%) males and 3(25%) females. In terms knee osteoarthritis grade, there was no significant difference between the groups (p=1.00). No significant differences were observed in any of the outcome measures neither at 2 weeks, nor at 4 weeks post-intervention between the groups (p>0.05) except for percentage change in segmental lean mass of the right leg at 2nd week and of the left leg at 4th week (p<0.05). Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis, however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits. NCT04654871. https://www.clinicaltrials.gov/ct2/show/NCT04654871.

Study on Management of Blood Transfusion Therapy in Patients with Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a chronic hemolytic disorder caused by inherited defects in the red blood cell membrane. This study discusses the treatment strategy for the decline in hemoglobin level in three HS probands with moderately severe or severe hemolysis and summarizes the appropriate laboratory tests that help improve clinical management of blood transfusion in HS patients. Three probands who were diagnosed with HS in our hospital and their family members were included in this study. Clinical data of the three families were reviewed to summarize their hematopoietic characteristics. DNA from all family members of the 3 HS probands was amplified by polymerase chain reaction (PCR) and sequenced by the Sanger method to assess genetic relation for HS. Based on the sequencing results, the type of mutated membrane protein in each proband was analyzed using the eosin-5′-maleimide (EMA) binding test and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The hemoglobin level was reduced in all 3 probands after different levels of infection. The fluorescence of EMA-labeled red blood cell (RBC) was decreased. DNA sequencing showed that His54Pro, Leu1858Val, and 6531-12C>T compound heterozygous mutations were present in the SPTA1 gene of patient I-1, Arg344Gln and c.609+86G>A heterozygous mutations were present in the SLC4A1 gene of patient II-1, and Leu2032Pro homozygous mutation was present in the SPTB gene of patient III-1. SDS-PAGE results demonstrated that the concentration of band 3 was reduced in II-1, whereas the levels of the corresponding mutant proteins in the other probands were unchanged. The family members of the respective patients presented mutations in major genes causing HS. The Leu2032Pro mutation identified in patient III-1 is a new missense mutation of the SPTB gene in the Chinese population that has never been reported in literature previously. The presence or absence of acute or chronic infections is a critical deciding factor for the treatment and clinical management of HS patient via blood transfusion. For patients with infections, hemoglobin concentration can be restored once the infection is controlled, thus obviating the need for proper infection control before blood transfusion.

P582 Association between serum ustekinumab concentrations and endoscopic disease activity in Crohn’s disease

Abstract Background Therapeutic drug monitoring, the measurement of serum biologic concentrations and immunogenicity, has become an important method in guiding the management of biologic therapy in patients with Crohn’s disease (CD). Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an approved therapy for patients with CD. However, few studies have explored the relationship between serum ustekinumab drug levels and outcomes in CD. Thus, the utility of serum ustekinumab drug levels in the management of CD remains unknown. The primary objective of the study was to evaluate the association between serum ustekinumab drug levels and endoscopic remission (ER) in CD. Secondary outcomes included evaluating the association between serum ustekinumab drug levels and clinical (CR), biochemical, and histological remission (HR). Methods Adult patients with CD maintained on ustekinumab were prospectively recruited at the time of routine colonoscopy from 2019 to 2021 at the Montreal University Health Centre, Montreal, Quebec. Clinical and demographic information was obtained from chart and patient review. CD symptom severity was assessed by the Harvey-Bradshaw Index (HBI), with clinical remission defined as an HBI score less than 5. Blood samples were drawn for measurement of serum ustekinumab drug level and C-reactive protein. Stool samples for fecal calprotectin were also collected. Elevated C-reactive protein and fecal calprotectin were defined as a value greater than 5 mg/L and 200 ug/g, respectively. Endoscopic remission was evaluated by the Simplified Endoscopic Score for Crohn’s Disease (SES-CD), with ER defined by an SES-CD score less than 3. If biopsies were taken, histological outcomes were recorded. HR was defined as inactive colitis. Results 53 patients were included in the study, of which 22 (41.5%) were in ER. Median [interquartile range] ustekinumab drug levels were not associated with ER (Figure 1. ER = 5.4 mg/L [2.6–9.4 mg/L], no ER = 4.3 mg/L [2.3–9.4 mg/L]; P=0.843). There was also no association between quartiles of ustekinumab drug levels and ER (P=0.772). In addition, there was no association observed between median ustekinumab drug level and CR (CR = 4.7 mg/L [2.7–8.3 mg/L], no CR = 3.8 mg/L [2.1–9.6 mg/L]; P=0.993) or HR (HR = 6.4 mg/L [3.5–9.5 mg/L], no HR = 3.7 mg/L [2.2–8.0 mg/L]); P=0.168). There was no association observed between median ustekinumab drug level and C-reactive protein or fecal calprotectin as well (P=0.158 and 0.923, respectively). Conclusion There was no association observed between serum ustekinumab drug levels and endoscopic remission. Further studies are required to validate our findings.