Indicator Of Treatment Success Research Articles

Impact of peri-implant keratinized mucosa width on the long-term reconstructive outcomes of peri-implantitis: A retrospective analysis with a follow-up up to 10 years.

To investigate the effect of mid-buccal peri-implant keratinized mucosa width (KMW) ≥2 mm or peri-implant KMW >0 mm and <2 mm on the long-term outcomes of peri-implantitis reconstructive treatment. Twenty-nine patients (40 implants; mean follow-up: 9.2 ± 1.4 years) with at least one implant affected by peri-implantitis and surgically treated through a reconstructive procedure followed by a submerged healing were included. Patients were categorized according to their initial KMW: Group 1 (KMW ≥2 mm) and Group 2 (KMW >0 mm and <2 mm). Peri-implant clinical and radiographic parameters and a dedicated composite outcome were assessed at different follow-up visits during supportive peri-implant therapy for up to 10 years. Regression analyses were utilized to identify possible risk/predictive indicators for probing pocket depth (PPD) change and treatment success at the latest follow-up. The mean PPD did not exhibit any statistical difference from the baseline to the latest follow-up between the groups at both patient and implant levels. Long-term treatment success was 46.6% (Group 1) and 42.6% (Group 2) at patient level, it was 42.8% (Group 1) and 33.3% (Group 2), respectively, at implant level (p > 0.05). Group 1 demonstrated significantly higher vertical defect depth reduction than Group 2 (p = 0.018). Presence of buccal bony wall and mean PPD at the baseline were found to be associated with mean PPD change, while KMW at 6 months following surgery was identified as the only significant indicator for treatment success (p < 0.05). Implants with KMW ≥2 mm did not present significantly better long-term clinical outcomes following reconstructive therapy than those exhibiting KMW >0 mm and <2 mm. However, KMW values at the end of healing phase following a submerged approach had a significant impact on long-term treatment success.

Systemic antibiotics in the surgical treatment of peri-implantitis: A randomized placebo-controlled trial.

To study the clinical, radiographic and microbiological outcomes after surgical treatment of peri-implantitis, with or without adjunctive systemic antibiotics. Eighty-four patients (113 implants) with peri-implantitis were randomized into three groups (A, amoxicillin and metronidazole; B, phenoxymethylpenicillin and metronidazole; or C, placebo). Treatment included resective surgery and implant surface decontamination with adjunctive antibiotics or placebo. Primary outcomes were probing pocket depth (PPD) reduction and marginal bone level (MBL) stability. Secondary outcomes were treatment success (defined as PPD ≤ 5 mm, bleeding on probing [BOP] ≤ 1site, absence of suppuration on probing [SOP] and absence of progressive bone loss of >0.5 mm), changes in BOP/SOP, mucosal recession (REC), clinical attachment level (CAL), bacterial levels and adverse events. Outcomes were evaluated for up to 12 months. The impact of potential prognostic indicators on treatment success was evaluated using multilevel logistic regression analysis. A total of 76 patients (104 implants) completed the study. All groups showed clinical and radiological improvements over time. Statistically significant differences were observed between groups for MBL stability (A = 97%, B = 89%, C = 76%), treatment success (A = 68%, B = 66%, C = 28%) and bacterial levels of Aggregatibacter actinomycetemcomitans and Tannerella forsythia, favouring antibiotics compared to placebo. Multiple regression identified antibiotic use as potential prognostic indicator for treatment success. Gastrointestinal disorders were the most reported adverse events in the antibiotic groups. Adjunctive systemic antibiotics resulted in additional improvements in MBL stability. However, the potential clinical benefits of antibiotics need to be carefully balanced against the risk of adverse events and possible antibiotic resistance.

Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines.

Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the "runaway" immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success.

Advancing Care in Severe Asthma: The Art of Switching Biologics.

Biologics targeting IgE, IL-5, IL-4/IL-13, and TSLP are crucial in severe asthma treatment. Research, including randomized controlled trials and real-world studies, has been conducted to assess their efficacy and identify patient characteristics that may predict positive responses. The effectiveness of switching biologics, especially given overlaps in treatment eligibility, and the clinical outcomes post-cessation are critical areas of investigation. This work reviews the effects of switching between these biologics and the indicators of treatment success or failure. Insights are primarily derived from real-world experiences, focusing on patients transitioning from one monoclonal antibody to another. Moreover, this review aims to provide insights into the effectiveness, safety, and broader implications of switching biologics, enhancing understanding for clinicians to optimize severe asthma management. The article underlines the importance of a patient-centered approach, biomarker assessment, and the evolving nature of asthma treatment in making informed decisions about biologic therapy.

Priorities for efficacy trials of gender-affirming hormone therapy with estrogen: collaborative design and results of a community survey.

Treatment guidelines for gender-affirming hormone therapy with estrogen (GAHT-E) recommend specific dosing regimens based on limited data. Well-controlled efficacy trials are essential to tailoring treatment to patient goals as the guidelines recommend. The goal of this study was to take a foundational step toward designing community-centered effectiveness trials for gender-diverse individuals seeking GAHT-E. Our team developed a cross-sectional survey based on broad clinical experience and consultation with our community advisory board. The survey included 60 items covering demographics, transition history, goals and priorities for treatment, indicators of treatment success, sexual function goals, and future research priorities. The survey was distributed during the summer of 2021, primarily through social networks designed for gender-expansive individuals seeking treatment with estrogen. A total of 1270 individuals completed the survey. Overall treatment goals most frequently rated "extremely important" or "very important" were the following: (1) improved satisfaction with life (81%), (2) appearing more feminine (80%), (3) appearing less masculine (77%), (4) improved mental health (76%), and (5) being seen as your true gender by others (75%). The three body characteristics most frequently rated "highest priority" or "high priority" among changes were the following: (1) facial hair (85%), (2) breast shape or size (84%), and (3) body shape (80%). The highest-rated research priority was comparing feminization with different routes of estrogen administration. The goals and experiences of individuals seeking GAHT-E are diverse. Future clinical trials of GAHT-E should be grounded in the needs and priorities of community stakeholders.

Bubonic plague: can the size of buboes be accurately and consistently measured with a digital calliper?

IntroductionConducting clinical research on treatments for emerging infectious diseases is often complicated by methodological challenges, such as the identification of appropriate outcome measures to assess treatment response and the lack of validated instruments available to measure patient outcomes. In bubonic plague, some studies have assessed bubo size as an indicator of treatment success, a measure widely assumed to be indicative of recovery. Evaluating this outcome however is challenging as there is no validated method for measuring bubo size. The aim of this study is to assess the accuracy and inter- and intra-rater agreement of artificial bubo measurements using a digital calliper to understand whether a calliper is an appropriate measurement instrument to assess this outcome.MethodsStudy technicians measured 14 artificial buboes made from silicone overlaid with artificial silicone skin sheets over the course of two training sessions. Each artificial bubo was measured by each study technician once per training session, following a Standard Operating Procedure. The objectives of this study are to (i) evaluate the accuracy of individual measurements against the true size of the artificial bubo when using a digital calliper, (ii) understand whether the characteristics of the artificial bubo influence measurement accuracy and (iii) evaluate inter- and intra-rater measurement agreement.ResultsIn total, 14 artificial buboes ranging from 52.7 to 121.6 mm in size were measured by 57 raters, generating 698 measurements recorded across two training sessions. Raters generally over-estimated the size of the artificial bubo. The median percentage difference between the measured and actual bubo size was 13%. Measurement accuracy and intra-rater agreement decreased as the size of the bubo decreased. Three quarters of all measurements had a maximum of 25% difference from another measurement of the same artificial bubo. Inter-rater agreement did not vary with density, size or presence of oedema of the artificial bubo.ConclusionsThe results of this study demonstrate the challenges for both individual and multiple raters to repeatedly generate consistent and accurate measurements of the same artificial buboes with a digital calliper.

Study protocol of an observational study in acute psychiatric home treatment: How does home treatment work? Identification of common factors and predictors of treatment success.

Systematic reviews indicated that home treatment is an effective and cost-saving alternative to conventional acute psychiatric treatment options. Treatment success has often been defined as areduction of hospital admissions. In the current study, symptoms and well-being are assessed regularly during treatment as an indicator for treatment success. Patients' characteristics such as diagnosis, age, substance use, and motivation for treatment were discussed as predictors for treatment success. Asecond focal point of the study lies in the examination of the therapeutic relationship in terms of the outcome, which has not yet been systematically investigated in home treatment. This is an observational study with aprospective naturalistic design. Measurements are carried out at baseline, during and at the end of treatment as well as at the 3‑month follow-up. Patients' characteristics as potential predictors for treatment success will be assessed at baseline. In addition, the perceived relationship between the patients and the team will be measured daily and weekly throughout the treatment. Treatment success is by the changes in symptoms and general well-being assessed weekly. We aim to include 82participants assigned to home treatment. Variance analyses with repeated measurements will be conducted to evaluate treatment success. By examining potential patient- and relationship-related predictors of treatment success, insights into relevant determining variables of treatment success in this setting are expected. The results might help to better identify who benefits the most from home treatment.

Change in Tissue Resistance during Irreversible Electroporation of Liver Tumors as an Indicator of Treatment Success: A Multicenter Analysis with Long-term Follow-up

Change in Tissue Resistance during Irreversible Electroporation of Liver Tumors as an Indicator of Treatment Success: A Multicenter Analysis with Long-term Follow-up

A comparison of mortality and indicators of treatment success of resuscitative endovascular balloon occlusion of aorta (REBOA): a systematic review and meta-analysis.

Emergency resuscitative thoracotomy (RT) is a recognised method of controlling non-compressible torso haemorrhage (NCTH) often in adjunct to emergency surgery. Recently, there is much debate regarding resuscitative endovascular balloon occlusion of aorta (REBOA) on its role in civilian trauma cases in controlling NCTH. This study aims to provide an updated review on in-hospital mortality rates in patients who underwent REBOA versus RT and standard care without REBOA (non-REBOA) and to identify the potential indicators of REBOA survival. Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to perform the study. All adult trauma cases were included, while pre-hospital, military and non-English studies were excluded. A literature search was done on studies from 01 January 2005 to 30 June 2020 using EMBASE, MEDLINE and COCHRANE databases. Risk of bias was assessed using the Methodological Index for Non-Randomised Studies (MINORS) tool. Meta-analysis was conducted using a random effects model and the DerSimonian and Laird estimation method. A significance level of p < 0.05 was used. Twenty-five studies were included in this study. The odds of in-hospital mortality of patients who underwent REBOA compared to RT was 0.18 (p < 0.01, 0.12-0.26). The odds of in-hospital survival of patients who underwent REBOA compared to non-REBOA was 1.28 (p = 0.62, 0.46-3.53). There was a significant difference found between survivors and non-survivors in terms of their pre-REBOA systolic blood pressure (SBP) (19.26mmHg, p < 0.01), post-REBOA SBP (20.73mmHg, p < 0.01), duration of aortic occlusion (- 40.57min, p < 0.01) and injury severity score (- 8.50, p < 0.01). REBOA has a potential for wider application in civilian settings, with our study demonstrating lower in-hospital mortality compared to RT. Prospective multi-centre studies are needed for further evaluation of the indications and feasibility of REBOA.Level of Evidence + Study Type: Level IV. Systematic review with meta-analysis. The online version contains supplementary material available at 10.1007/s12055-022-01413-3.

Deep learning prediction of non-perfused volume without contrast agents during prostate ablation therapy

The non-perfused volume (NPV) is an important indicator of treatment success immediately after prostate ablation. However, visualization of the NPV first requires an injection of MRI contrast agents into the bloodstream, which has many downsides. Purpose of this study was to develop a deep learning model capable of predicting the NPV immediately after prostate ablation therapy without the need for MRI contrast agents. A modified 2D deep learning UNet model was developed to predict the post-treatment NPV. MRI imaging data from 95 patients who had previously undergone prostate ablation therapy for treatment of localized prostate cancer were used to train, validate, and test the model. Model inputs were T1/T2-weighted and thermometry MRI images, which were always acquired without any MRI contrast agents and prior to the final NPV image on treatment-day. Model output was the predicted NPV. Model accuracy was assessed using the Dice-Similarity Coefficient (DSC) by comparing the predicted to ground truth NPV. A radiologist also performed a qualitative assessment of NPV. Mean (std) DSC score for predicted NPV was 85% ± 8.1% compared to ground truth. Model performance was significantly better for slices with larger prostate radii (> 24 mm) and for whole-gland rather than partial ablation slices. The predicted NPV was indistinguishable from ground truth for 31% of images. Feasibility of predicting NPV using a UNet model without MRI contrast agents was clearly established. If developed further, this could improve patient treatment outcomes and could obviate the need for contrast agents altogether.Trial Registration Numbers Three studies were used to populate the data: NCT02766543, NCT03814252 and NCT03350529.

Determinants of health-related quality of life in recently detoxified patients with severe alcohol use disorder

BackgroundHealth-related quality of life (HRQoL) is an important clinical outcome in Alcohol Use Disorder (AUD) and is considered as a relevant indicator of treatment success. While a better understanding of the factors affecting HRQoL would enable to adjust patients’ care to favour treatment outcome, the determinants of HRQoL in AUD remain unclear. This study aims at describing HRQoL in AUD patients and at identifying its best predictors.Methods53 recently detoxified patients with severe AUD (sAUD) underwent a cognitive assessment and filled in a HRQoL questionnaire dedicated to AUD patients (Alcohol Quality of Life Scale; AQoLS), as well as questionnaires concerning socio-demographics, alcohol history, sleep quality, depression, anxiety and impulsivity. 38 healthy controls (HC) underwent the same assessment (except AQoLS) in order to identify the altered cognitive and clinical variables that could potentially be determinants of HRQoL in sAUD.ResultssAUD patients reported that alcohol affects their HRQoL mainly in the “negative emotions”, “control”, “relationships”, and “sleep” domains. Compared to HC, they were impaired on episodic memory, working memory, executive functions, and processing speed tasks. They also reported lower sleep quality, higher depression, anxiety and impulsivity. No association was found between AQoLS total score and socio-demographics, cognitive performance, or sleep quality in patients. We found a significant correlation between HRQoL and depression/anxiety as well as impulsivity. Anxiety and impulsivity were indeed the only significant predictors of HRQoL, explaining 47.7% of the variance.ConclusionAnxiety and impulsivity are crucial determinants of HRQoL in recently detoxified sAUD patients. Since anxiety and impulsivity are frequent issues in addiction and especially in AUD, they should be particularly considered by clinicians to favour treatment outcomes.

How does plasticity of migration help tumor cells to avoid treatment: Cytoskeletal regulators and potential markers.

Tumor shrinkage as a result of antitumor therapy is not the only and sufficient indicator of treatment success. Cancer progression leads to dissemination of tumor cells and formation of metastases - secondary tumor lesions in distant organs. Metastasis is associated with acquisition of mobile phenotype by tumor cells as a result of epithelial-to-mesenchymal transition and further cell migration based on cytoskeleton reorganization. The main mechanisms of individual cell migration are either mesenchymal, which depends on the activity of small GTPase Rac, actin polymerization, formation of adhesions with extracellular matrix and activity of proteolytic enzymes or amoeboid, which is based on the increase in intracellular pressure caused by the enhancement of actin cortex contractility regulated by Rho-ROCK-MLCKII pathway, and does not depend on the formation of adhesive structures with the matrix, nor on the activity of proteases. The ability of tumor cells to switch from one motility mode to another depending on cell context and environmental conditions, termed migratory plasticity, contributes to the efficiency of dissemination and often allows the cells to avoid the applied treatment. The search for new therapeutic targets among cytoskeletal proteins offers an opportunity to directly influence cell migration. For successful treatment it is important to assess the likelihood of migratory plasticity in a particular tumor. Therefore, the search for specific markers that can indicate a high probability of migratory plasticity is very important.

Extracranial arteriovenous malformations demonstrate dysregulated TGF-β/BMP signaling and increased circulating TGF-β1

Extracranial arteriovenous malformations (AVMs) are characterized by anomalous arterial-to-venous connections, aberrant angiogenesis, local inflammation and hypoxia, and disorganized histological architecture; however, the precise molecular perturbations leading to this phenotype remain elusive. We hypothesized that extracranial AVM tissue would demonstrate deregulation of the TGF-β/BMP signaling pathway, which may serve as a potential target in the development of molecular-based therapies for AVMs. AVM tissue was harvested during resection from 10 patients with AVMs and compared to control tissue. Blood was collected from 14 AVM patients and 10 patients without AVMs as controls. Expression of TGF-β/BMP pathway components was analyzed using RT-PCR, western blotting, and immunohistochemistry. Circulating levels of TGF-β1 were analyzed by ELISA. Paired t tests were utilized to perform statistical analysis. The mRNA levels of TGF-β1, ALK1, Endoglin (ENG), Smad6, Smad7, and Smad8 were significantly elevated in AVM tissue when compared to controls. Protein levels of TGF-β1 and Smad3 were elevated in AVM tissue while protein levels of BMP-9, ALK1, Smad1, Smad6, and Smad8 were significantly decreased in AVMs. Immunohistochemistry demonstrated increased TGF-β1 in the perivascular cells of AVMs compared to normal controls, and circulating levels of TGF-β1 were significantly higher in AVM patients. Patients with AVMs demonstrate aberrant TGF-β/BMP expression in AVM tissue and blood compared to controls. Targeting aberrantly expressed components of the TGF-β/BMP pathway in extracranial AVMs may be a viable approach in the development of novel molecular therapies, and monitoring circulating TGF-β1 levels may be a useful indicator of treatment success.

Mechanisms of quality-of-life improvement in treatment for alcohol use disorder.

For individuals in alcohol use disorder (AUD) treatment, many argue that holistic indicators such as quality of life (QoL) should be more consistently used in addition to drinking-related indicators. QoL increases from pre- to post-AUD treatment, but the mechanisms are unclear. The present study examined the roles of positive and negative affect in QoL change during AUD treatment and additionally explored the relationship between QoL change and medication adherence. We examined the mediating roles of end-of-treatment positive affect (i.e., vigor) and negative affect (i.e., stress and tension) in the relationship between baseline (BL) and 26-week QoL among participants in the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence study randomized to medication management (MM; n = 468) or medication management plus combined behavioral intervention (MMCBI; n = 479) for AUD. We also explored whether changes in QoL were associated with medication adherence. Change in psychological health QoL was mediated by increased vigor (i.e., positive affect) and decreased stress, and change in environmental QoL was mediated by decreased stress. There were also differences by treatment group, with stress mediating changes in environmental QoL among participants in MM, and vigor mediating changes in psychological health QoL among participants in MMCBI. Medication adherence was not associated with greater QoL after controlling for posttreatment alcohol use. The present study identified potential mechanisms of QoL change in AUD treatment, thus contributing to the growing knowledge surrounding alternative indicators of treatment success for AUD treatment and recovery. Targeting affective states and stress during treatment may improve QoL and recovery outcomes for persons with AUD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Frequency and Predictors of Unsuppressed HIV Viral Load Among People with HIV in Nyaruguru District, Rwanda

BackgroundBy the end of 2015, epidemiological studies approximated 37 million people living with HIV (PLHIV) and 46.3% of them were initiated to antiretroviral therapies. From the 90-90-90 strategy, by 2020 at global level, 90% of all people living with HIV were expected to suppress viral load (VL). Although VL suppression is an important indicator of treatment success in PLHIV, studies on this indicator remain scarce in Rwanda where the prevalence of HIV is 3% with 9% for non-suppression. This work, thus, determined the prevalence of VL non-suppression and its associated predictors among PLHIV.MethodsA cross-sectional study was conducted among 637 PLHIV enrolled in healthcare services between 2016 and 2017 in Nyaruguru district. Socio-demographic, treatment, clinical, immunological and VL data were extracted from medical records. Bivariate and multivariate logistic regression analyses were performed to determine associated factors with VL suppression considering 95% confidence intervals and statistical significance of p<0.005.ResultsMore than half of participants were female (57.77%). The prevalence of unsuppressed HIV VL was 8.9% and 88.7% of respondents were satisfied with the service provided. Males were more likely to be unsuppressed HIV VL [aOR = 3.02; 95% CI (1.19–7.64), p = 0.02] than females. Higher likelihoods of VL non-suppression were among those with history of clinical failure [aOR = 3.14; 95% CI (1.70–14.03), p = 0.034] or history of treatment interruption [aOR = 8.29; 95% CI (2.60–26.42) p = 0.002]. Those with a bad perception toward the whole life treatment were more likely to be unsuppressed [aOR = 4.32; 95% CI (1.98–18.99), p = 0.049] than their counterparts.ConclusionSex, treatment interruption, bad perception toward the whole life treatment, clinical failure and lack of confidentiality were the major predictors of being unsuppressed. More efforts on counseling HIV patients to improve their knowledge would drop levels of VL non-suppression, so improving the quality of service should be prioritized to increase suppression.

Early pharmacokinetic evaluation of anti-tubercular treatment as a good indicator of treatment success in pulmonary tuberculosis patients on a retreatment regimen

Early pharmacokinetic evaluation of anti-tubercular treatment as a good indicator of treatment success in pulmonary tuberculosis patients on a retreatment regimen

High Volume PRP Therapy.

The PRP method is widely used to support healing and regeneration in musculoskeletal and aesthetic medicine. The current literature, however, brings contradictory reports as to its effectiveness, which, at least in part, should be attributed to the diversity of methods for producing the concentrate, including the use of various volumes of whole blood, single vs double centrifugation vs filtration, use of thrombin vs calcium chloride to activate the process, and, finally, the use of an anticoagulant. The aim of the study was to retrospectively evaluate the effectiveness of high-volume PRP therapy with the Angel® system (Arthrex) in our patients. A total of 400 therapies were performed on 299 patients. The most frequently represented indications were knee osteoarthritis (OA), n = 164, including mild (n = 30), moderate (n = 38), and advanced (n = 96) stage; lumbar degenerative disc disease (LDDD), n = 54; rotator cuff injuries (RCI), n = 52; lumbar spinal stenosis (LSS), n = 37; cervical degenerative disc disease (CDDD), n = 17; and shoulder OA, n = 12. Therapies for LDDD and LSS patients were additionally divided with respect to the route of administration (periradicular vs epidural). The assessment tool was the modified Macnab scale. Follow-up examinations were performed at two and six months after PRP administration. Indicators of treatment success were defined as the percentage of satisfactory results and the percentage ratio of satisfactory results to non-satisfactory results after 2 and 6 months of follow-up (S/NS2 and S/NS6). For the advanced stage of knee OA, the results were compared in three age groups (under 66, 67-73 and over 74). For the entire treatment group, the mean S/NS2 ratio was 1.56; in the group of the most frequently represented indications, the highest satisfaction ratio was obtained in LDDD (2.84), and the lowest in the group of RCI (0.96). The mean value of the S/ NS6 ratio was 2.24, being the highest in mild knee OA (4.79) and CDDD (4.67), and the lowest in shoulder OA (0.72). In the age group over 74 years, the frequency of non-satisfactory results shows an increase in patients with advanced knee OA. 1. High-volume PRP therapy can be used as a local regenerative and anti-inflammatory treatment, demonstrating the highest efficacy in early knee OA and CDDD. 2. High PRP therapy demonstrates a high safety profile. 3. The final effects of the therapy develop over a period of several months of follow-up and depend on the severity of the degenerative process and the patient&apos;s age.

Belumosudil for Patients with Chronic Graft-Versus-Host Disease: Combined Analysis of Failure-Free Survival (FFS) in the KD025-208 and Pivotal Rockstar Trials

ABSTRACTIntroduction: Belumosudil (KD025) is a novel oral selective rho-associated coiled-coil-containing kinase-2 (ROCK2) inhibitor specifically designed for the treatment of cGVHD following an allogeneic hematopoietic cell transplant. It has been evaluated in the phase 2a dose-finding (KD025-208) and the pivotal phase 2 ROCKstar trials. Patients with cGVHD in the KD025-208 trial received belumosudil after failure of 1 to 3 prior systemic lines of therapy (LOTs), and those in the ROCKstar trial received belumosudil after failure of 2 to 5 prior systemic LOTs. The best overall response rate (95% CI) achieved, which was the primary end point, was 72% (64%-78%) across the 3 dosages (belumosudil 200 mg QD, 200 mg BID and 400 mg QD) that were studied across the 2 trials. This led to the recent FDA approval of the 200-mg QD dose for the treatment of adult and pediatric patients aged ≥12 years with cGVHD after failure of ≥2 prior systemic LOTs. FFS was a secondary end point in both trials.FFS is an established composite indicator for treatment success in cGVHD, as it incorporates recurrent malignancy, nonrelapse mortality (NRM) and the absence of subsequent cGVHD therapy. Historic rates of FFS in a prior large observational study of patients with cGVHD after second-line systemic therapy were 56% at 6 months, 45% at 12 months and 31% at 24 months (Inamoto, Blood 2013). Given limited data from contemporaneous clinical trials on FFS and prognostic factors of treatment failure, we studied pooled FFS and its determinants from the KD025-208 and ROCKstar trials.Methods: A total of 186 patients from the KD025-208 (n=54) and ROCKstar (n=132) trials treated with belumosudil 200 mg QD, 200 mg BID or 400 mg QD were analyzed . The median duration of belumosudil treatment was 9.9 months (range, 0.4-44.7 months). Prior therapies included tacrolimus (58%), sirolimus (46%), extracorporeal photopheresis (42%), mycophenolate mofetil (27%), ibrutinib (27%), ruxolitinib (21%) and cyclosporine (5%).Results: At enrollment, 70% of patients had severe cGVHD according to NIH global score, 52% had ≥4 organs involved and 37% received >3 prior LOTs. Overall, belumosudil was well tolerated, with drug discontinuations occurring in 10% of patients due to possible drug-related adverse events. The median FFS was 14 months. The estimated overall FFS (95% CI) rates were 75% (68%-81%), 54% (47%-61%) and 38% (29%-47%) at 6, 12 and 24 months, respectively (Table 1 and Figure). Reasons for failure included recurrent malignancy (6%), NRM (7%) and the addition of a new systemic cGVHD therapy (43%). Factors associated with increased risk of treatment failure (1-FFS) in both univariate and multivariate analyses (Table 2) included progressive onset of cGVHD (multivariate hazard ratio [HR]=2.1 [1.2-3.4]), absence of glucocorticoids in upfront therapy for cGVHD (HR=2.2 [1.2-4.0]) and ≥2 prior LOTs (HR=3.7 [1.2-12.2]).Conclusion: Treatment with belumosudil resulted in high FFS rates compared with historic benchmarks in cGVHD refractory to prior LOTs. Both NRM and relapse rates were low with the use of belumosudil. We identified distinct prognostic factors for FFS that can inform risk stratification and prognostication of patients being treated with belumosudil. [Display omitted] DisclosuresLazaryan: Humanigen: Membership on an entity's Board of Directors or advisory committees; Avrobio: Membership on an entity's Board of Directors or advisory committees; Kadmon: Consultancy. Cutler: Mesoblast: Consultancy; Syndax: Consultancy; Omeros: Consultancy; Incyte: Consultancy; CareDx: Consultancy; Mallinckrodt: Consultancy; Pfizer: Consultancy; Kadmon: Consultancy; Editas: Consultancy; Cimeio: Consultancy; Deciphera: Consultancy; Jazz: Consultancy. Yang: Kadmon: Current Employment. Ieyoub: Kadmon: Current Employment. Eiznhamer: Kadmon: Current Employment. Blazar: BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Carisma Therapeutics, Inc: Research Funding; Rheos Medicines: Research Funding; Tmunity Therapeutics: Other: Co-founder; Equilibre Pharmaceuticals Corp: Research Funding; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Lee: Amgen: Research Funding; Incyte: Research Funding; Novartis: Other: clinical trials, Research Funding; Pfizer: Research Funding; Kadmon: Research Funding; Takeda: Research Funding; Syndax: Research Funding; AstraZeneca: Research Funding; JANSSEN: Other; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees. Pavletic: Center for Cancer Research: Research Funding; National Cancer Institute: Research Funding; National Institutes of Health: Research Funding; Celgene: Research Funding; Actelion: Research Funding; Eli Lilly: Research Funding; Pharmacyclics: Research Funding; Kadmon: Research Funding.

Viral suppression among HIV-positive patients on antiretroviral therapy in northwestern Nigeria: an eleven-year review of tertiary care centre records, January 2009\u2013December 2019

BackgroundHuman Immuno-Deficiency Virus (HIV) remains one of the world’s significant public health challenges. Viral suppression is the key indicator for treatment success in People living with HIV (PLHIV). We determined the level of viral suppression, and its associated factors among PLHIV attending Federal Medical Centre Katsina (FMC Katsina), Nigeria.MethodsThis retrospective descriptive cross-sectional study was conducted on 913 HIV positive adults enrolled in care between January 2009 and December 2019. Information on socio-demographics, clinical, immunological, Viral load (VL), and other relevant parameters were extracted from the patients’ care records. The primary outcome was the proportion of patients that achieved viral suppression. We also analyzed variables that were associated with VL suppression.ResultsOf 913, records of 831 (91.0%) registered patients were analyzed. During the period, 751 (90.4%) achieved viral suppression, 427 (51.4%) had CD4 counts ≥ 500 and 477 (57.4%) were on HAART for ≥ 5 years. Majority, 793 (95.4%) were on first-line HAART regimen (Tenofovir-Lamivudine-Dolutegravir or Abacavir-Lamivudine-Dolutegravir), and 809 (97.4%) in the non-advanced stage (WHO stages 1 and 2). The median (interquartile range) of viral load was 20 (20–40) vs 19,989 (3311–110,340) cp/ml in virally suppressed, and unsuppressed respectively. Factors associated with viral suppression included being unemployed (Adjusted OR [AOR] 4.9, 95% CI 2.771, 8.539), educated (AOR 4.2, 95% CI 1.098, 16.223), having a baseline CD4 count ≥ 500 cells/µl (AOR 2.7, 95% CI 1.588, 4.625), and being on first line HAART regimen [AOR 7.0, 95% CI 3.220, 15.648].ConclusionsOur study demonstrated a good viral suppression among PLHIV on HAART. Variables associated with viral suppression included unemployment, formal education, high baseline CD4 count, and first line HAART regimen.

Switching to the Dry-Powder Inhaler Easyhaler®: A Narrative Review of the Evidence.

Asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. Optimal control of these conditions is a constant challenge for both physicians and patients. Poor inhaler practice is widespread and is a substantial contributing factor to the suboptimal clinical control of both conditions. The practicality, dependability, and acceptability of different inhalers influence the overall effectiveness and success of inhalation therapy. In this paper, experts from various European countries (Finland, Germany, Hungary, Italy, Poland, Spain, and Sweden) address inhaler selection with special focus on the Easyhaler® device, a high- or medium–high resistance dry-powder inhaler (DPI). The evidence examined indicates that use of the Easyhaler is associated with effective control of asthma or COPD, as shown by the generally accepted indicators of treatment success. Moreover, the Easyhaler is widely accepted by patients, is reported to be easy to learn and teach, and is associated with patient adherence. These advantages help patient education regarding correct inhaler use and the rational selection of drugs and devices. We conclude that switching inhaler device to the Easyhaler may improve asthma and COPD control without causing any additional risks. In an era of climate change, switching from pressurized metered-dose inhalers to DPIs is also a cost-effective way to reduce emissions of greenhouse gases. Enhanced feature (slides, video, animation) (MP4 43768 kb)Supplementary InformationThe online version contains supplementary material available at 10.1007/s41030-021-00174-5.