Usual Therapy Research Articles

Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. ObjectivesThe aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. MethodsPatients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. ResultsA total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro–B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± −21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization–based criteria for HFpEF vs 7% in the medical arm (P = 0.02). ConclusionsAF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.

Baseline characteristics from a retrospective, observational, US-based, multicenter, real-world (RW) study of avelumab first-line maintenance (1LM) in locally advanced/metastatic urothelial carcinoma (la/mUC) (PATRIOT-II).

465 Background: The JAVELIN Bladder 100 clinical trial demonstrated a significant overall survival and progression-free survival benefit with avelumab 1LM + best supportive care (BSC) vs BSC alone for la/mUC not progressing on platinum-based chemotherapy (PBC). PATRIOT-II aims to describe RW data for avelumab 1LM treatment (tx) of patients (pts) with la/mUC. Methods: PATRIOT-II collected data from pts with la/mUC treated in 37 geographically dispersed oncology practices/communities and academic centers in the US. Pts who initiated avelumab 1LM following PBC were retrospectively enrolled and will be followed up via medical record review for 52 weeks post avelumab 1LM initiation. This analysis focused on pt characteristics and tx data from la/mUC diagnosis through the PBC period and at avelumab 1LM initiation. Disease and PBC tx characteristics, as well as response to PBC, were assessed. All analyses were descriptive. Results: A total of 160 pts were enrolled (Table), 118 (74%) were white, non-Hispanic, 16 (10%), were Black, Asian, or Hispanic, and the rest unknown; 102 (64%) were current or former smokers. 77 (48%) were tested for PD-L1 via various assays, with 44 (57%) of those tumor samples reported as positive. 1L PBC was cisplatin-based in 100 (63%) of pts and carboplatin-based in 60 (38%). Pts received a median of 4 PBC cycles (interquartile range [IQR], 3-6) for a median of 13 weeks (IQR, 10-17). 31 (19%) discontinued PBC due to unacceptable side effects/toxicity. Best observed response was complete response in 21 (13%), partial response in 109 (68%), and stable disease in 17 (11%), with the remainder unknown. Median time to first imaging was 10 weeks (IQR, 5-14) after PBC initiation. 23 (14%) were hospitalized while receiving PBC, and 25 (16%) were seen in the emergency department. Pts proceeded to avelumab 1LM at a median of 4 weeks (IQR, 3-6) following PBC completion. Avelumab was administered at 800 mg every 2 weeks in 130 (81%), 10 mg/kg in 15 (9%), &lt;800 mg in 8 (5%), and &gt;800 mg in 7 (4%) pts. Conclusions: This ‘RW’ study offers valuable insights into characteristics and outcomes of pts with la/mUC treated in the US. Baseline factors, tx patterns and response to PBC were consistent with usual therapy paradigms in the 1L induction setting. Ongoing trials are evaluating the optimal number of PBC cycles and predictive biomarkers. Limitations include the retrospective nature, lack of randomization and central review, potential selection and confounding biases. [Table: see text]

Vojta Therapy and Conservative Physical Therapy versus Physical Therapy Only for Lumbar Disc Protrusion: A Comparative Cohort Study from Romania

Background: Lumbar disc herniation (LDH) is a common condition caused by degenerative lesions of the lumbar intervertebral discs, due to aging or lifting weights. For patients with LDH, a comparative study was conducted to understand the benefits of Vojta therapy and conservative physical therapy versus physical therapy only. The aim of this paperwork was to help physicians select interventions which are most appropriate for this disease. Methods: Seventy-seven patients with LDH from two cohorts were included in analysis (Group A and Group B). Group A benefited from 30 min of Vojta therapy procedures, in addition to the usual physical therapy treatment, and group B received a conservatory physical therapy program. The subjects were assessed with the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), mobility tests, muscle strength tests and the Nottingham Health Profile (NHP) questionnaire. Results: Pain intensity and disability decreased in both groups (p = 0.000 in experimental group and 0.047 in control group for VAS score and p = 0.000 for ODI score in both groups). Moreover, mobility, strength and health-related quality of life scores increased significantly both in groups A and B (p = 0.000 in both). Conclusions: After two weeks of interventions, we saw greater differences in pain intensity, disability level, mobility, strength, and health-related quality of life scores in both study groups, but not across the groups. This was not the case between the groups.

In obese hypertensives cholecalciferol inhibits circulating TH17 cells but not macrophage infiltration on adipose tissue

In arterial hypertension, increased Th17 cells and reduced Tregs are the hallmarks of immunological dysfunction and the basis for the investigation of immunomodulatory drugs. Although cholecalciferol is not a primary immunomodulator, it has recognized action on immune cells, leading us to hypothesise if cholecalciferol can induce a more tolerogenic phenotype in obese hypertensives.In a phase-2, single-centre, randomised, open, 24-week trial, we assigned adults with obesity-associated hypertension and vitamin D deficiency to receive usual therapy plus 50,000 IU/week of cholecalciferol or usual therapy alone. The primary endpoint was the percentual variation in T CD4+, T CD8+, Tregs, and Th17 cells. Secondary endpoints included the percentual variation in Th1, Tc1, Tc17, and monocytes and variation in the number of perivascular and non-perivascular macrophages, T CD4+ and T CD8+ lymphocytes in subcutaneous abdominal adipose tissue. A control group of 12 overweight normotensives was also evaluated for peripheral immune cells.A total of 36 obese hypertensives were randomised, 18 in each group. In comparison with normotensive controls, hypertensives presented higher percentages of T lymphocytes (p = 0.016), Tregs (p = 0.014), and non-classical monocytes (p < 0.001). At week 24, Th17 cells increased in control group (p = 0.017) but remained stable in cholecalciferol group. For Tregs, downregulation towards the values of normotensive controls was observed (p = 0.003), and in multivariate analysis, an increased loading in the setting of the cells of adaptive immunity observed (eigenvalue 1.78, p < 0.001). No changes were documented for monocytes. In adipose tissue, a baseline negative correlation between vitamin D and perivascular macrophages was observed (r = −0.387, p = 0.024) that persisted in the control group (r = −0.528, p = 0.024) but not in the cholecalciferol group, which presented an increase in non-perivascular macrophages (p = 0.029) at week 24. No serious adverse events were reported for all the participants.In this trial, we found that supplementation with cholecalciferol interfered with peripheral and adipose tissue immune cell profile, downregulating peripheral Th17 cells, but increasing the number of infiltrating subcutaneous adipose tissue macrophages. (Funded by Núcleo Estudos Hipertensão da Beira Interior; EudraCT number: 2015–003910-26).

New Developments in Cardiology with Implications in Clinical Practice

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death among patients with chronic heart failure and a left ventricular ejection fraction of 40% or less. Whether SGLT2 inhibitors are effective in patients with a higher left ventricular ejection fraction remains less certain. Methods: We randomly assigned 6,263 patients with heart failure and a left ventricular ejection fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart failure (which was defined as either an unplanned hospitalization for heart failure or an urgent visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis. Results: Over a median of 2.3 years, the primary outcome occurred in 512 of 3,131 patients (16.4%) in the dapagliflozin group and in 610 of 3,132 patients (19.5%) in the placebo group (hazard ratio: 0.82; 95% confidence interval [CI], 0.73−0.92; P < .001). Worsening heart failure occurred in 368 patients (11.8%) in the dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio: 0.79; 95% CI: 0.69−0.91); cardiovascular death occurred in 231 (7.4%) and 261 (8.3%) patients, respectively (hazard ratio: 0.88; 95% CI: 0.74−1.05). Total events and symptom burden were lower in the dapagliflozin group than in the placebo group. Results were similar among patients with a left ventricular ejection fraction of 60% or more and those with a left ventricular ejection fraction of less than 60%, and results were similar in prespecified subgroups, including patients with or without diabetes. The incidence of adverse events was similar in the two groups. Conclusions: Dapagliflozin reduced the combined risk of worsening heart failure or cardiovascular death among patients with heart failure and a mildly reduced or preserved ejection fraction (Funded by AstraZeneca; DELIVER ClinicalTrials.gov number, NCT03619213.). Comments: The DELIVER trial can be considered a landmark trial in the therapy of heart failure. While the role of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) was well established by the DAPA-HF trial, its role in heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) was undetermined. The EMPEROR trials demonstrated the benefits of empagliflozin in HFrEF (EMPEROR-Reduced) and HFpEF (EMPEROR-Preserved). However, while EMPEROR-Preserved showed a mortality reduction and symptom benefit in HFmrEF, only symptom benefit was demonstrated in HFpEF. On the other hand, the DELIVER trial has demonstrated, for the first time, a mortality benefit in HFpEF and HFmrEF patients with dapagliflozin. The benefits of dapagliflozin were the same in patients with EF < 60% and EF > 60%. Strengths: The trial evaluated a large sample size and a diverse population, demonstrating the benefits in a variety of patient populations seen in clinical practice. While dapagliflozin (like all agents) remains more useful in HFrEF, this is the first agent which has shown a mortality benefit in HFpEF, which is otherwise a difficult-to-treat population. Implications: As a consequence of the EMPEROR-Reduced and the DELIVER trials, the ACC/AHA/HFSA Heart Failure guidelines 2022 recommend the use of SGLT2 inhibitors in HFpEF with a Class 2A recommendation. For day-to-day practice, it is now possible to prescribe an evidence-based and effective agent in patients with HFpEF, something which was not possible before. The following trials demonstrate the conflicting evidence available in deciding targets for preventive cardiology. To start, the completely Indian MERIFACS study gives an interesting insight into the concept of the “Metabolic Syndrome”.

Prasugrel — gone, but not forgotten

AbstractHuman immunodeficiency virus (HIV) infection and certain retroviral therapies are associated with an increased risk of atherosclerosis with plaque rupture resulting in acute coronary syndromes. Therefore, there is often a need to co‐prescribe antiretroviral and cardiovascular therapies, including antiplatelet agents. Antiplatelet agents, such as the P2Y12 receptor antagonists clopidogrel and prasugrel, require activation by cytochrome P450 3A4 (CYP3A4). The P2Y12 receptor antagonist ticagrelor is also metabolised by CYP3A4. Pharmacokinetic enhancers, such as ritonavir and cobicistat, are utilised to increase the systemic exposure of certain agents within multidrug HIV regimens and are potent CYP3A4 inhibitors. Using these drugs together can result in unintended and undesirable drug–drug interactions. A 55‐year‐old male with a history of HIV presented to the emergency department with central chest pain. He was found to have had a non‐ST‐elevation myocardial infarction and was commenced on dual antiplatelet therapy including ticagrelor, anticoagulation and statin therapy, in addition to his usual HIV therapy, Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide). A drug–drug interaction between Genvoya and ticagrelor was identified by the pharmacist, and the patient was switched to prasugrel on the pharmacist's recommendation. Although prasugrel was delisted from the Pharmaceutical Benefits Scheme (PBS) in July 2020, it remains accessible as a non‐PBS medicine. Prasugrel should be considered the P2Y12 antagonist of choice for patients who are on HIV regimens containing a pharmacokinetic enhancer such as ritonavir or cobicistat.

Target therapy forBRAFmutated anaplastic thyroid cancer: a clinical and molecular study

Anaplastic thyroid carcinoma (ATC) has a poor survival. The combination of Dabrafenib plus Trametinib (DT) had a significant impact in survival of BRAF p.V600E patients. However, durable responses may be compromised by resistance. We aim to present our experience with DT in BRAF positive ATC patients and compare the outcomes with usual therapy, and to study tumor molecular alterations in the DT group. Patients treated between May 2018 and April 2022 in a tertiary referral center, assessed for BRAF status were included. Patients were divided in three groups: BRAF p.V600E treated with DT, BRAF wild type (WT) under multimodal therapy (MT), and BRAF WT under compassionate care (CC). Response was assessed monthly in the first 6 months and every 3 months afterwards, by RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared with the log-rank test. Twenty-seven ATC patients were included (DT = 9, MT = 8, and CC = 10). Median OS was 475 days for DT, 156 days for MT, and 39 days for CC (P < .001). At 12 months, only patients in the DT group were alive (71%). Median PFS was 270 days, in the DT group, compared with less than 32 days in BRAF WT (P < .001). No severe adverse events were reported. Molecular profiling showed that in one of the four clinical progressions, a pathogenic NRAS mutation was found. Our results show a significant real-world efficacy of Dabrafenib plus Trametinib in both survival and recurrence compared with standard treatment, with a good safety profile.

Сахарный диабет в исходе хронического панкреатита: особенности течения и терапии

Aim: To demonstrate a clinical case of a patient with diabetes mellitus secondary to chronic pancreatitis, who needs not only compensation for carbohydrate metabolism, but also correction of exocrine pancreatic insufficiency. Key points. The patient noted a significant improvement in well-being against the background of adequate hypoglycemic therapy (nighttime metformin, sodium-glucose co-transporter type 2 inhibitors and glucagon-like peptide-1 receptor agonist, basal insulin glargine) and enzyme-replacement therapy with pancreatin minimicrospheres at a dose of 50,000 IU on main meals and up to 25,000 ED at snacks. When evaluating the glycemic profile of continuous glucose monitoring showed stabilization of blood glucose at the target range. According to the results of laboratory tests, the patient showed not only normalization of carbohydrate metabolism, but also an initially reduced level of total protein, vitamins and minerals. Conclusion. Administration of drugs used to treat patients with type 2 diabetes mellitus for the management of patients with diabetes secondary to chronic pancreatitis is justified. At the same time, the addition of insulin is often necessary. For this group of patients, the enzyme replacement therapy of exocrine pancreatic insufficiency is as important for the correction of metabolic disorders as the usual hypoglycemic therapy. Keywords: pancreatogenic diabetes mellitus, chronic pancreatitis, exocrine pancreatic insufficiency.

Impact of the COVID-19 pandemic on treatment approaches of multiple myeloma

Cancer has been recognized as one of the major comorbidities associated with severe outcomes in the novel coronavirus disease 19 (COVID-19) patients. Compared to those with solid tumors and those without cancer, patients with hematologic malignancies appear to have more severe clinical outcomes and higher rate of mortality from COVID-19. This was particularly demonstrated during the early pandemic period. The COVID-19 pandemic has posed additional challenges in the management of hematologic malignancies, including establishing prompt diagnoses, providing optimal treatment while minimizing the risk and sequela of COVID-19 infection. Given these challenges, clinical practice guidelines and recommendations on management of hematologic malignancies during the COVID-19 pandemic were developed and proposed based on expert panels and individual expert opinions. Multiple myeloma is the second most common hematologic malignancy. The management of patients with multiple myeloma during the COVID-19 pandemic is extremely challenging as patients with multiple myeloma are particularly vulnerable to infections due to underlying humoral and cellular immune dysfunction, cytotoxic chemotherapy, immunotherapy, cellular therapy and steroid regimens, advanced age, and the presence of other comorbidities. In this paper, we attempt to provide a general review of clinical practice management patterns during and after the COVID-19 pandemic in patients with multiple myeloma and demonstrate how changes evolved as more knowledge was gained over time. Specifically, we review the impact of the pandemic on treatment approaches, supportive care, and vaccinations for patients with newly diagnosed multiple myeloma, relapsed/refractory multiple myeloma, patients with stable disease, and those with precursor states like monoclonal gammopathy and smoldering multiple myeloma. During early pandemic several changes were noted in myeloma care including minor delay in time to treatment initiation and tendency to defer autologous stem cell transplant. However, after 2022, with the advent of effective vaccines and treatment strategies the severity of COVID-19 infection decreased and care of myeloma returned to usual management, incorporating transplant, CART and multiple novel immune therapy approaches. Finally, we highlight the importance of meticulous vaccination schedule for patients with myeloma for all common viral, bacterial pathogens and vaccination against COVID-19.

No evidence for stratified exercise therapy being cost-effective compared to usual exercise therapy in patients with knee osteoarthritis: Economic evaluation alongside cluster randomized controlled trial

BackgroundA stratified approach to exercise therapy may yield superior clinical and economic outcomes, given the large heterogeneity of individuals with knee osteoarthritis (OA). ObjectiveTo evaluate the cost-effectiveness during a 12-month follow-up of a model of stratified exercise therapy compared to usual exercise therapy in patients with knee OA, from a societal and healthcare perspective. MethodsAn economic evaluation was conducted alongside a cluster-randomized controlled trial in patients with knee OA (n = 335), comparing subgroup-specific exercise therapy for a ‘high muscle strength subgroup’, ‘low muscle strength subgroup’, and ‘obesity subgroup’ supplemented by a dietary intervention for the ‘obesity subgroup’ (experimental group), with usual (‘non-stratified’) exercise therapy (control group). Clinical outcomes included quality-adjusted life years – QALYs (EuroQol-5D-5 L), knee pain (Numerical Rating Scale) and physical functioning (Knee Injury and Osteoarthritis Outcome Score in daily living). Costs were measured by self-reported questionnaires at 3, 6, 9 and 12-month follow-up. Missing data were imputed using multiple imputation. Data were analyzed through linear regression. Bootstrapping techniques were applied to estimate statistical uncertainty. ResultsDuring 12-month follow-up, there were no significant between-group differences in clinical outcomes. The total societal costs of the experimental group were on average lower compared to the control group (mean [95% confidence interval]: € 405 [-1728, 918]), albeit with a high level of uncertainty. We found a negligible difference in QALYs between groups (mean [95% confidence interval]: 0.006 [-0.011, 0.023]). The probability of stratified exercise therapy being cost-effective compared to usual exercise therapy from the societal perspective was around 73%, regardless of the willingness-to-pay threshold. However, this probability decreased substantially to 50% (willingness-to-pay threshold of €20.000/QALY) when using the healthcare perspective. Similar results were found for knee pain and physical functioning. ConclusionsWe found no clear evidence that stratified exercise therapy is likely to be cost-effective compared to usual exercise therapy in patients with knee OA. However, results should be interpreted with caution as the study power was lower than intended, due to the Coronavirus disease (COVID-19) pandemic.

Lennox Gastaut syndrome. Case report and mini-review

Introduction: Lennox-Gastaut syndrome is a form of childhood epilepsy that has a dramatic negative impact on the physical and developmental health of the patient. Being an age-related disorder, it is characterized by seizures, characteristic electroencephalogram, psychomotor retardation and behavioral disturbances. It is more common in males and usually begins before the age of eight years and peaks between the ages of three and five years. Case presentation: This was a 5-year-old patient who was born prematurely product of which presented sequelae of hypoxia, who around 4 months was diagnosed with epilepsy, for which he received double antiepileptic therapy based on levetiracetam and valproic acid with partial control of his seizures until before the age of 5 years, At this time it was necessary to include a third drug to the usual therapy called clobazam, for which with the adjustment of doses until the age of 8 years he achieved a better control, however the sequelae of infantile cerebral palsy are marked.Conclusion: It is one of the most difficult syndromes to treat and is often resistant to commonly used antiepileptic drugs. The long-term prognosis is poor; although epilepsy usually improves, complete absence of seizures is rare and, instead, psychological and psychiatric disorders worsen over time

COACH2MOVE: THE STORY OF IMPLEMENTING A PERSON-CENTERED PHYSICAL THERAPY APPROACH IN CLINICAL PRACTICE

Abstract Coach2Move is a person-centered physical therapy approach to promote physical activity among community-dwelling older adults, which consists of motivational interviewing and other motivational strategies. Coach2Move has been implemented in the Netherlands with 52 physical therapists and 294 patients in 16 practices. Implementation has led to better outcomes (increased physical activity, improved functional mobility, and lower levels of frailty) in fewer treatment sessions compared with usual care physical therapy treatment. Implementing was carried out using the following steps: 1) an e-assessment to determine the baseline level of knowledge regarding Coach2Move of the participating therapists; 2) two education days in Motivational Interviewing and Coach2Move specific motivational strategies; 3) three unique peer-assessment meetings and 4) a retest of the e-assessment one year later. We will discuss our rationale for selecting implementation strategies and which barriers and facilitators we have experienced in implementing successful scientific research in daily clinical practice.

Upper limb training using visual feedback for children with cerebral palsy

Purpose: This study aimed to investigate that if upper limb visual feedback training added to the usual therapy was effective on upper limb functions in children with cerebral palsy. Methods: Thirty-eight children with cerebral palsy (4-18 years) participated in the study. The participants were randomly assigned into two groups. Study group (n=19, mean age 8.50±3.40, 53% female) received visual feedback training plus usual therapy twice a week for 8 weeks, 16 sessions in total, while control group (n=19, mean age 10.60±3.80, 42% female) received only usual therapy. The participants’ Gross Motor Function Classification System levels were between I-III and spasticity levels were between ‘0’ to ‘1+’ according to Modified Ashworth Scale. Upper limb range of motion (ROM), grip and pinch strength, hand skills (Minnesota Manual Dexterity Test (MMDT)), and functional abilities (Childhood Health Assessment Questionnaire (CHAQ)) were assessed before and after treatment. Results: The change amount in shoulder flexion (p=0.004) and abduction (p=0.01), supination (p=0.019) and wrist flexion (p=0.004) and extension (p=0.00) ROM values; bilateral MMDT scores (p=0.003) were statistically significantly improved in study group compared to control group. Conclusion: Adding visual feedback training to the usual therapy program of children with cerebral palsy was found to be effective in some outcome measurements such as upper limb ROM and hand skills. In the long-term rehabilitation process, this new training method may be an alternative additive option for children, families, and physiotherapists.

Diet Therapy Using a Small Rice Bowl among Japanese Men with Diabetes: A Randomized Controlled Trial.

This study aimed to investigate the effectiveness at 1 and 3 months of using a smaller rice bowl for diet therapy among Japanese men with type 2 diabetes. A parallel-group randomized controlled trial was conducted at a medical clinic in Japan. The participants were men with type 2 diabetes mellitus, aged 20-80 years, with glycosylated hemoglobin <8.5%, and who ate rice one or more times per day at home. The intervention group (36 men) received a small rice bowl from which to eat the usual diet therapy, and the control group (38 men) received only the usual diet therapy. The changes in weight and body mass index among the intervention group at 1 month were significantly higher than those in the control group. There were no significant differences between the two groups at 3 months. The effects of using a small rice bowl were minor and short-term.

The Effects of Four Weeks of Chiropractic Spinal Adjustments on Blood Biomarkers in Adults with Chronic Stroke: Secondary Outcomes of a Randomized Controlled Trial.

Certain blood biomarkers are associated with neural protection and neural plasticity in healthy people and individuals with prior brain injury. To date, no studies have evaluated the effects chiropractic care on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-II (IGF-II) and glial cell-derived neurotrophic factor (GDNF) in people with stroke. This manuscript reports pre-specified, exploratory, secondary outcomes from a previously completed parallel group randomized controlled trial. We evaluated differences between four weeks of chiropractic spinal adjustments combined with the usual physical therapy (chiro + PT) and sham chiropractic with physical therapy (sham + PT) on resting serum BDNF, IGF-II and GDNF in 63 adults with chronic stroke. Blood samples were assessed at baseline, four weeks (post-intervention), and eight weeks (follow-up). Data were analyzed using a linear multivariate mixed effects model. Within both groups there was a significant decrease in the mean log-concentration of BDNF and IGF-II at each follow-up, and significant increase log-concentration of GDNF at eight-weeks' follow-up. However, no significant between-group differences in any of the blood biomarkers at each time-point were found. Further research is required to explore which factors influence changes in serum BDNF, IGF-II and GDNF following chiropractic spinal adjustments and physical therapy.

Updates on the Diagnosis and Management of Glaucoma.

Glaucoma is the leading cause of blindness throughout the world (after cataracts); therefore, general physicians should be familiar with the diagnosis and management of affected patients. Glaucomas are usually categorized by the anatomy of the anterior chamber angle (open vs narrow/closed), rapidity of onset (acute vs chronic), and major etiology (primary vs secondary). Most glaucomas are primary (ie, without a contributing comorbidity); however, several coexisting ophthalmic conditions may serve as the underlying etiologies of secondary glaucomas. Chronic glaucoma occurs most commonly; thus, regular eye examinations should be performed in at-risk patients to prevent the insidious loss of vision that can develop before diagnosis. Glaucoma damages the optic nerve and retinal nerve fiber layer, leading to peripheral and central visual field defects. Elevated intraocular pressure (IOP), a crucial determinant of disease progression, remains the only modifiable risk factor; thus, all current treatments (medications, lasers, and operations) aim to reduce the IOP. Pharmacotherapy is the usual first-line therapy, but noncompliance, undesirable adverse effects, and cost limit effectiveness. Laser and surgical treatments may lower IOP significantly over long periods and may be more cost effective than pharmacotherapy, but they are plagued by greater procedural risks and frequent treatment failures. Traditional incisional procedures have recently been replaced by several novel, minimally invasive glaucoma surgeries with improved safety profiles and only minimal decreases in efficacy. Minimally invasive glaucoma surgeries have dramatically transformed the surgical management of glaucoma; nevertheless, large, randomized trials are required to assess their long-term efficacy.

Consider this SGLT2 inhibitor for patients with HF with preserved ejection fraction

The addition of empagliflozin to usual therapy reduced hospitalization risk, regardless of patients' diabetes status.

The Effectiveness of Manual Therapy in the Cervical Spine and Diaphragm, in Combination with Breathing Reeducation Exercises, in Patients with Non-Specific Chronic Neck Pain: Protocol for Development of Outcome Measures and a Randomized Controlled Trial.

Until now, non-specific chronic neck pain has mainly been considered as a musculoskeletal system dysfunction, with associated psychological involvement due to its prolonged or recurrent nature. However, patients with non-specific chronic neck pain frequently additionally exhibit respiratory dysfunction. Emerging evidence suggests that addressing the respiratory dysfunction in these patients will provide additional therapeutic benefits in musculoskeletal and respiratory-related outcomes for several reasons (biomechanical, biochemical, and psychological). Motor control dysfunction of the muscles surrounding the spine (diaphragm included) negatively affects the mechanics and biochemistry of breathing (pH-homeostasis). An impaired and ineffective breathing pattern has been recognized as the primary source of many unexplained symptoms (anxiety, depression, confusion, chest pain, hypocapnia, and breathlessness) in patients with non-specific chronic neck pain. The proposed protocol's purpose is dual: to assess the relative effectiveness of manual therapy in the cervical spine and the diaphragm, in combination with breathing reeducation exercises, along with cervical spine manual therapy or usual physical therapy care on the underlying dysfunctions in patients with non-specific chronic neck pain via a randomized controlled clinical trial, and to validate part of the outcome measures. Several musculoskeletal and respiratory dysfunction outcomes will be employed to delimit the initial extent and level of dysfunction and its resolution with the treatments under study.

RF32 | PSUN49 To Repeat or Not to Repeat: The Question of Aldosterone and Renin Variability

Abstract Plasma aldosterone concentration (PAC), renin levels and aldosterone-renin ratio (ARR) are used to screen for primary aldosteronism (PA). A recent study (Yozamp et al. Hypertension 2021) reported substantial intraindividual variability of PAC and ARR (using plasma renin activity) in the context of usual antihypertensive therapy. The intraindividual variability of PAC and direct renin concentration (DRC), a more widely used measurement of renin, in the absence of interfering medications is unknown but important where a single ARR is used to screen for PA. The aim of this study was to evaluate the intraindividual variability of PAC, DRC and ARR in a cohort of patients with and without PA. Patients who attended an Endocrine Hypertension Service from May 2017 to July 2021 with at least two ARR measurements off interfering medications were retrospectively evaluated. While the measurements were performed at several hospital and community laboratories, the same analyser was used. PA was confirmed using the seated saline suppression test following an abnormal ARR &amp;gt;70 pmol/L: mU/L. PAC and DRC variability was calculated as coefficient of variation (CV=standard deviation/mean×100) and percent difference (PD=difference between highest and lowest values/mean×100). A total of 223 patients were analysed (55% female, median age 52 years), including 162 with PA (25% with unilateral disease). Significant variability in both PAC and DRC was observed in the PA group (CV: 24%, 41%; PD: 46%, 76% respectively) and non-PA group (CV: 22%, 40%; PD: 38%, 65% respectively), which was higher than the assays’ analytical variability. The ARR was also highly variable within individuals, in both the PA group (CV: 42%; PD: 74%) and non-PA group (CV: 37%; PD: 61%). Variability was not significantly different between PA subtypes, and persisted irrespective of age, gender and degree of hypertension. Sixty-two patients (39%) with PA could have had a missed diagnosis if the ARR had not been repeated, i.e., had at least one ARR &amp;lt;70 pmol/L: mU/L, while 28 (46%) without PA had at least one abnormal ARR &amp;gt; 70. Intraindividual variability in PAC, DRC and ARR occurs in a significant number of patients being investigated for PA. These results support the need for at least two ARR on separate occasions before PA is excluded or further investigated. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.

RObotic-Assisted Rehabilitation for balance and gait in Stroke patients (ROAR-S): study protocol for a preliminary randomized controlled trial

BackgroundStroke, the incidence of which increases with age, has a negative impact on motor and cognitive performance, quality of life, and the independence of the person and his or her family, leading to a number of direct and indirect costs. Motor recovery is essential, especially in elderly patients, to enable the patient to be independent in activities of daily living and to prevent falls. Several studies have shown how robotic training associated with physical therapy influenced functional and motor outcomes of walking after stroke by improving endurance and walking strategies.Considering data from previous studies and patients’ needs in gait and balance control, we hypothesized that robot-assisted balance treatment associated with physical therapy may be more effective than usual therapy performed by a physical therapist in terms of improving static, dynamic balance and gait, on fatigue and cognitive performance.MethodsThis is an interventional, single-blinded, preliminary randomized control trial. Twenty-four patients of both sexes will be recruited, evaluated, and treated at the UOC Rehabilitation and Physical Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from January to December 2022. Patients will be randomized into two groups: the experimental group will perform specific rehabilitation for balance disorder using the Hunova® robotic platform (Movendo Technology srl, Genoa, IT) for 3 times a week, for 4 weeks (12 total sessions), and for 45 min of treatment, in addition to conventional treatment, while the conventional group (GC) will perform only conventional treatment as per daily routine. All patients will undergo clinical and instrumental evaluation at the beginning and end of the 4 weeks of treatment.ConclusionsThe study aims to evaluate the improvement in balance, fatigue, quality of life, and motor and cognitive performance after combined conventional and robotic balance treatment with Hunova® (Movendo Technology srl, Genoa, IT) compared with conventional therapy alone. Robotic assessment to identify the most appropriate and individualized rehabilitation treatment may allow reducing disability and improving quality of life in the frail population. This would reduce direct and indirect social costs of care and treatment for the National Health Service and caregivers.Trial registrationClinicalTrials.gov NCT05280587. Registered on March 15, 2022.