Term Therapy Research Articles

Comparison of Effects of Injectable Semaglutide and Dulaglutide on Oxidative Stress and Glucose Variability in Patients with Type 2 Diabetes Mellitus: A Prospective Preliminary Study.

Recent trials have shown that glucagon-like peptide-1 receptor agonists considerably reduce atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Oxidative stress, a surrogate marker of cardiovascular risk, is associated with glucose variability. However, to the best of our knowledge, no studies have compared the effects of injectable semaglutide and dulaglutide therapies on oxidative stress and glucose variability assessed via continuous glucose monitoring (CGM). This study aimed to analyze and compare the effects of semaglutide and dulaglutide therapies on oxidative stress and glucose variability as assessed through CGM. This is an open-label, multicenter, randomized, prospective, parallel-group comparison study. Overall, 37 patients with T2DM treated with dulaglutide for at least 12weeks were randomized into two groups: one receiving continuous dulaglutide therapy (n = 19) and one receiving injectable semaglutide therapy (n = 18) groups. The coprimary endpoints were changes in the results of the diacron-reactive oxygen metabolites test, an oxidative stress marker, and CGM-evaluated glucose variability after 24weeks. The secondary endpoint was changes in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores. Switching to semaglutide therapy was better than continuous dulaglutide therapy in reducing oxidative stress, glucose variability, and glycated hemoglobin levels. Conversely, continuous dulaglutide therapy was better than semaglutide therapy in terms of DTSQ scores for "Convenience" and "Recommend." Injectable semaglutide therapy may be more effective than dulaglutide therapy in ameliorating oxidative stress and regulating glucose metabolism, including glucose variability, in patients with T2DM, while dulaglutide therapy may be more effective in terms of treatment satisfaction. UMIN-CRT ID: UMIN000042670 (registered 7 December 2020).

To what extent can remote treatment address geographic barriers to psychotherapy?

Abstract Background The COVID-19 pandemic led to a surge in remote psychotherapy, suggesting it might also be a good way to overcome distance barriers to treatment post-pandemic. This study examined patterns of receiving psychotherapy before and after the COVID-19 outbreak, as well as patients’ perceptions of remote care. We conducted an internet survey of 400 Israelis who received psychotherapy in 2020 and 10 in-depth interviews with patients. Results 57% of patients from Israel's geographic periphery reported receiving remote treatment, compared to 30% of patients from central Israel (p < 0.01). Among those who began treatment before the onset of the pandemic, 76% reported receiving remote treatment or combined remote and face-to-face treatment after the pandemic's outbreak. In contrast, only half of those who began treatment after the onset of the pandemic received remote treatment. The interviews indicated that it is harder to start treatment and establish a therapeutic alliance with the therapist remotely than to continue therapy that had started face-to-face. Patients who experienced remote therapy were more likely than others to rate it as effective as face-to-face therapy in terms of its ability to achieve treatment goals (44% vs. 20%), to foster dialogue on sensitive issues (48% vs. 34%) and to create a therapeutic relationship with the therapist (41% vs. 25%). Additionally, they were less likely to identify interpersonal communication difficulties as a drawback of remote therapy (55% vs. 78%) and more likely to be willing to continue using it post-pandemic (25% vs. 5%), (all p < 0.01). Conclusions The findings suggest that for some patients, remote psychotherapy can be an effective way to address geographic barriers to psychotherapy. However, most patients still prefer face-to-face therapy. Offering remote treatment after establishing a therapeutic connection via face-to-face treatment will probably be more popular among consumers than strictly remote care. Key messages • For some patients, remote psychotherapy can be an effective way to address geographic barriers to psychotherapy, especially when a therapeutic alliance has already been established. • Most patients prefer face-to-face therapy. However, patients who experienced remote care were more likely to rate it as effective as face-to-face therapy and to continue using it after the pandemic.

SARS-CoV-2 infection correlates with male benign prostatic hyperplasia deterioration.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) affects extra-respiratory systems, with small-scale studies showing worsened male lower urinary tract symptoms (LUTS) after coronavirus disease 2019 (COVID-19). This study explores the correlation between SARS-CoV-2 infection and male benign prostatic hyperplasia (BPH) complications using large-scale real world data. All male patients attending the public healthcare system in Hong Kong receiving alpha-blocker monotherapy for LUTS from 2021 to 2022 were included in this study. Patients with and without positive polymerase chain reaction (PCR) test for SARS-CoV-2 are selected as the exposure group and control group, respectively. Baseline characteristics are retrieved, with propensity score matching performed to ensure balance of covariates between the two groups. BPH complications were then compared and subgroup analyses were performed. After propensity score matching, 17,986 patients were included for analysis, among which half had PCR-confirmed SARS-CoV-2 infection (n=8993). When compared to controls, the SARS-CoV-2 group demonstrated statistically significant higher incidence of retention of urine (4.55% vs. 0.86%, p<0.001), haematuria (1.36% vs. 0.41%, p<0.001), clinical urinary tract infection (UTI) (4.31% vs. 1.49%, p<0.001), culture-proven bacteriuria (9.02% vs. 1.97%, p<0.001) and addition of 5ARI (0.50% vs. 0.02%, p<0.001). Subgroup analysis demonstrated similar differences across different age groups. There are no statistically significance differences in incidence of retention, haematuria, or addition of 5ARI across different COVID-19 severities. SARS-CoV-2 infection is associated with increased incidence of urinary retention, haematuria, UTI and the addition of combination therapy in the short term, regardless of COVID-19 severity. This is the largest study demonstrating the detrimental urological effects of SARS-CoV-2 infection.

Effects of Conservative Oxygen Therapy versus Conventional Oxygen Therapy on the Mortality in ICU Patients: A Meta-Analysis.

To compare the effects of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in ICU. Searching for randomized controlled clinical trials (RCT) on the effect of conservative oxygen therapy and conventional oxygen therapy on the mortality of critically ill patients in computer databases, including PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang, with postdate before August 2022. We have two researchers evaluating the quality of the literature included and extracting data as per the inclusion and exclusion criteria and then analyzed it with RevMan 5.4 statistical software. Primary outcome included short-term mortality (28-day mortality or ICU mortality); secondary outcome included 90-day mortality, ICU length of stay, hospital length of stay, incidence of new organ dysfunction in ICU, incidence of new infection in ICU, and incidence of ICUAW. A total of 5779 subjects were included in 10 articles, including 2886 in the conservative oxygen therapy group and 2893 in the conventional oxygen therapy group. The meta-analysis showed that conservative oxygen therapy had an advantage over conventional oxygen therapy in terms of short-term mortality (P=0.03). Subgroup analysis based on different conservative oxygen targets showed that this advantage was statistically significant when the target is set above 90% (RR = 0.76, 95% CI = 0.62∼0.94, P=0.01), while there was no significant difference between conservative oxygen therapy and conventional oxygen therapy when the target is set below 90% (RR = 0.95, 95% CI = 0.79∼1.16, P=0.63). In addition, in terms of the incidence of new infections in the ICU (P=0.03) and the incidence of ICUAW (P=0.03), conservative oxygen therapy also had advantages over conventional oxygen therapy, and the difference was statistically significant. But in terms of 90-day mortality (P=0.61), ICU length of stay (P=0.96), hospital length of stay (P=0.47), and incidence of new organ dysfunction in ICU (P=0.61), there was no significant difference between conservative oxygen therapy and conventional oxygen therapy. Compared with conventional oxygen therapy, conservative oxygen therapy can reduce the short-term mortality of severe patients, especially when the conservative oxygen therapy target is set above 90%. And it can also reduce the incidence of ICU new infections and ICUAW, while having no effect on 90-day mortality, ICU length of stay, and hospital length of stay.

OXA-48 Dominance Meets Ceftazidime-Avibactam: A Battle Against Life-Threatening Carbapenem-Resistant Klebsiella pneumoniae Infections in the Intensive Care Unit.

Objective In this study, we aimed to describe the outcomes in ICU patients with bloodstream infection (BSI) or ventilatory-associated pneumonia (VAP) due to carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ceftazidime-avibactam treatment at a tertiary care university hospital. Methods Patients aged 18 years or older who were admitted to the Anesthesiology and Reanimation ICU at Bursa Uludag University Faculty of Medicine Hospital between June 13, 2021, and July 16, 2023, and diagnosed with BSI or VAP due to CRKPwere included in this study. Results A total of 42 patients treated with ceftazidime-avibactam were included. Total crude mortality rates were 33.3% on day 14 and 54.8% on day 30. Mortality rates on the 14th and 30th days were 37.5% and 62.5% in patients with BSI and 27.8% and 44.4% in patients with VAP, respectively. There was no statistically significant difference between monotherapy and combination therapy in terms of mortality rates on days 14 and 30, respectively (3/11 vs. 11/31, p=0.620; 5/11 vs. 18/31, p=0.470). Immunosuppression (10/11 vs. 13/31, p=0.005), the Sequential Organ Failure Assessment (SOFA) score ≥8(at the initiation of treatment; 19/25 vs. 4/17, p<0.001), INCREMENT-CPE score ≥10 (12/16 vs. 3/10, p=0.024) and longer duration (in days) from culture collection to treatment initiation (5.0 ± 0.61 vs. 3.11 ± 0.48, p=0.024) were found to have a statistically significant effect on 30-day mortality. In multivariate analysis, a SOFA score≥8at the initiation of treatment (p=0.037, OR: 17.442, 95% CI: 1.187-256.280) was found to be a significant risk factor affecting mortality (30-day). Conclusion The mortality rates of patients with CRKP infection who were followed up in the ICU were found to be high, and it was observed that whether ceftazidime-avibactam treatment was given as a combination or monotherapy did not affect mortality.Further multicentre studies with a larger number of patientsare needed to gain a comprehensive understanding of the topic, given that this treatment is typically reserved for documented infections.

A European Cost-Utility Analysis of the MiniMed™ 780G Advanced Hybrid Closed-Loop System Versus Intermittently Scanned Continuous Glucose Monitoring with Multiple Daily Insulin Injections in People Living with Type 1 Diabetes.

Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. In this study, a cost-utility analysis of the MiniMed™ 780G AHCL system (MM780G) versus intermittently scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries. Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were modeled. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied. Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy. Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in health care costs between countries, the health economic outcomes differed. In all included countries, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.

Epicardial Adipose Tissue Changes during Statin Administration in Relation to the Body Mass Index: A Longitudinal Cardiac CT Study

The epicardial adipose tissue (EAT) is the visceral fat located between the myocardium and the pericardium. We aimed to perform a longitudinal evaluation of the epicardial adipose tissue using an advanced computer-assisted approach in a population of patients undergoing Cardiac CT (CCT) during statin administration, in relation to their body mass index (BMI). We retrospectively enrolled 95 patients [mean age 62 ± 10 years; 68 males (72%) and 27 females (28%)] undergoing CCT for suspected coronary artery disease during statin administration. CCT was performed at two subsequent time points. At the second CCT, EAT showed a mean density increase (−75.59 ± 7.0 HU vs. −78.18 ± 5.3 HU, p &lt; 0.001) and a volume decrease (130 ± 54.3 cm3 vs.142.79 ± 56.9 cm3, p &lt; 0.001). Concerning coronary artery EAT thickness, a reduction was found at the origin of the right coronary artery (13.26 ± 5.2 mm vs. 14.94 ± 5.8, p = 0.001) and interventricular artery (8.22 ± 3.7 mm vs. 9.13 ± 3.9 mm, p = 0.001). The quartile (Q) attenuation percentage (%) distribution of EAT changed at the second CCT. The EAT % distribution changed by the BMI in Q1 (p = 0.015), Q3 (p = 0.001) and Q4 (p = 0.043) at the second CCT, but the normal-BMI and overweight/obese patients showed a similar response to statin therapy in terms of quartile distribution changes. In conclusion, statins may determine significant changes in EAT quantitative and qualitative characteristics detected by CCT; the BMI influences the EAT composition, but statins determine a similar response in quartile distribution’s variation, irrespective of the BMI.

Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease.

Polyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the de novo formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-α-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p<0.0001] compared to those with anti-AGAL antibodies [n=15]. Sera from anti-AGAL antibody-negative and -positive patients had less inhibitory effects on PRX-102 (rescued activity: 89 ± 6% versus 85 ± 7% and 49 ± 26% versus 25 ± 32%; both p<0.0001). Enzyme stability assays demonstrated that AUCs in anti-AGAL-negative sera (n=20) were 7.6-fold higher for PRX-102, while AUCs of both enzymes in anti-AGAL-positive sera (n=6) were decreased. However, AUC for PRX-102 was 33% of non-anti-AGAL-positive sera treated PRX-102 and 5-fold higher compared to agalsidase-beta. Anti-PEG antibodies had no significant effects on serum half-life of PRX-102, probably due to low titers. Conceivably, therapy efficacy may be superior under next-generation PRX-102 therapy compared to current enzyme replacement therapies in terms of reduced inhibitory effects of anti-AGAL and minor inhibitory effects of anti-PEG antibodies.

Treat-to-target versus high-intensity statin treatment in patients with or without diabetes mellitus: a pre-specified analysis from the LODESTAR trial

The impact of titrated versus fixed intensity statin therapy in patients with coronary artery disease (CAD) and diabetes mellitus (DM) remains to be elucidated. This was a pre-specified analysis of patients with and without DM from the LODESTAR trial. Patients with CAD were randomly assigned to receive either a treat-to-target strategy with a target LDL-C level of 50-70mg/dL or a high-intensity statin treatment. Primary outcome was the 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. Secondary outcomes were safety endpoints. This trial is registered with ClinicalTrials.gov, NCT02579499. Between September 9, 2016 and November 27, 2019, 4400 patients with CAD were enrolled in the LODESTAR trial. The median age was 65 years (interquartile range, 59-73 years), 3172 (72%) were male, and 1468 (33%) had DM at baseline. There was no significant difference in the occurrence of the primary outcome between the treat-to-target group and high-intensity statin group among patients with DM (10.5% versus 11.1%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69-1.29, p=0.70) and those without DM (6.9% versus 7.5%, HR 0.93, 95% CI 0.71-1.21, p=0.58). Among patients without DM, there was a trend towards a lower risk of new-onset DM in the treat-to-target group (8.4% versus 10.4% in the high-intensity statin group, HR 0.79, 95% CI 0.62-1.01; p=0.06). In patients with CAD, a treat-to-target LDL-C strategy of 50-70mg/dL as the goal was comparable to high-intensity statin therapy in terms of 3-year clinical efficacy and safety outcomes regardless of the presence of DM. Sam Jin Pharmaceutical, Seoul, Korea and Chong Kun Dang Pharmaceutical, Seoul, Korea.

Curcumin‐loaded nanomedicines as therapeutic strategy in malaria management

AbstractMalaria, a parasitic protozoan disease widespread in tropical climates, is transmitted by Plasmodium spp. Many people are affected by this significant public health disease, which has a high incidence of illness and mortality worldwide. Because drug‐resistant parasites are on the rise, there are not enough controls on mosquitoes, and there are not any malaria vaccinations. Malaria is particularly challenging in developing countries. Antimalarial drugs approved by Food and Drug Administration are the main options for combating and preventing malaria; also the control of transmission at the level of mosquitoes is important. Current antimalarial chemotherapeutic therapies have significant clinical flaws such as Plasmodium resistance, the drugs that call for the development of novel drug candidates. To combat malaria, nanotechnology may give a viable alternative that is both more effective and safer than current treatment options. Nanotechnology‐based curcumin formulations have proved to overcome the limitations of current therapies in terms of optimum therapeutic benefits, safety, and cost‐efficiency, which increases a patient's capacity to adhere to prescribed medicine. The limits of current malaria therapies and the need to employ nanotechnological curcumin to treat malaria were addressed and discussed in this paper.

Current affairs in the use of medical ozone. Biological effects. Mechanisms of action

Introduction. Oxygen-ozone therapy stands as a medically endorsed practice confirmed by numerous international clinical studies. Various authors have illustrated the beneficial clinical outcomes of ozone therapy in terms of its capacity to regulate redox balance, cellular inflammatory responses, and adaptation to ischemia/reperfusion processes. Ozone therapy extends to encompass a range of viral infections, inflammatory disorders, and degenerative ailments, used as both monotherapy and as an adjunct to unified conventional therapies. Material and methods. Narrative literature review study. Bibliographic search was conducted using the PubMed, Hinari, and SpringerLink databases, as well as the National Center of Biotechnology Information and Medline. Articles published between 1990 and 2022 were selected using various combinations of keywords, including “ozone”, “ozone therapy”, “mechanisms of ozone action”, “biological effects of ozone”, “antioxidant effect”, “anti-inflammatory effect” and “immunomodulatory effect.” Information regarding ozone’s mechanisms of action was identified and processed. Following the database information processing and search criteria, a total of 475 full-text articles were found. The final bibliography consists of 52 relevant sources that were deemed representative of the materials published on the topic of this synthesis article. Results. The effects of ozone on oxygen metabolism are explained by changes in the rheological properties of blood, including inhibition of erythrocyte aggregation and stimulation of 2,3-diphosphoglycerate in erythrocytes, favoring the transport and delivery of oxygen to tissues while facilitating the substantial elimination of nitric oxide and increasing blood flow. Intracellular triatomic oxygen enhances the oxidative carboxylation of pyruvate, stimulating ATP production, which also contributes to reducing peripheral vascular resistance. Conclusions. Ozone generates a moderate oxidative stress. Yet, it can set off several beneficial biochemical mechanisms that reactivate both the intra- and extracellular antioxidant systems and reverse chronic oxidative stress in various inflammatory and degenerative processes. Ozone induces a mild activation of the immune system by triggering neutrophil activation and stimulating the synthesis of certain cytokines (IL-2, TNF-α, IL-6, and IFN-γ), thereby initiating a complete cascade of immune responses. Ozone therapy yields the following biological reactions: optimization of blood circulation and oxygen delivery to ischemic tissue, regulation of cellular antioxidant enzymes, initiation of a slight immune system activation, and enhancing the release of growth factors.

Sleep Deprivation Impairs Human Cognitive Reappraisal Ability: A Randomized Controlled Trial.

This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm. A randomizedpretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later. Mean valence ratings of SD group were more negative than SC group's (p < 0.05) and mean arousal ratings of SD group were higher than SC group's (p < 0.01). Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation.

The Impact of the CYP2D6 and CYP1A2 Gene Polymorphisms on Response to Duloxetine in Patients with Major Depression.

Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.

Platelet P2Y12 signalling pathway in the dysregulated immune response during sepsis.

Sepsis is a complicated pathological condition in response to severe infection. It is characterized by a strong systemic inflammatory response, where multiple components of the immune system are involved. Currently, there is no treatment for sepsis. Blood platelets are known for their role in haemostasis, but they also participate in inflammation through cell-cell interaction and the secretion of inflammatory mediators. Interestingly, an increase in platelet activation, secretion, and aggregation with other immune cells (such as monocytes, T-lymphocytes and neutrophils) has been detected in septic patients. Therefore, antiplatelet therapy in terms of P2Y12 antagonists has been evaluated as a possible treatment for sepis. It was found that blocking P2Y12 receptors decreased platelet marker expression and limited attachment to immune cells in some studies, but not in others. This review addresses the role of platelets in sepsis and discusses whether antagonizing P2Y12 signalling pathways can alter the disease outcome. Challenges in studying P2Y12 antagonists in sepsis also are discussed. LINKED ARTICLES: This article is part of a themed issue on Platelet purinergic receptor and non-thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc.

Efficacy of antiresorptive agents in fibrous dysplasia and McCune Albright syndrome, a systematic review and meta-analysis.

Fibrous dysplasia (FD) is a rare skeletal disorder in which normal bone is replaced by a fibro-osseous tissue, resulting in possible deformities and fractures. The aim of this systematic review and meta-analysis was to synthesize the available evidence on the use of antiresorptive drugs in FD in terms of changes in bone turnover markers (BTMs), bone mineral density (BMD), and reducing pain. Three databases were searched in October 2022, with an update in July 2023. Of the 1037 studies identified, 21 were retained after eligibility assessment. A random-effects model was used to calculate global effect size and the corresponding standard error. Pamidronate and Denosumab were the most reported drugs in a total of 374 patients assessed. The initiation of treatments was accompanied by an average reduction of 40.5% [CI95% -51.6, -29.3] in the bone resorption parameters, and 22.0% [CI95% -31.9, -12.1] in the parameters of bone formation after 6-12months. BMD was increased in both FD lesions and in the unaffected skeleton. Pain was reduced by 32.7% [CI95% -52.7, -12.6] after 6-12 months of treatment, and by 44.5% [CI95% -65.3, -23.6] after a mean 41.2 months of follow-up. The variation in pain was highly correlated to variation in bone resorption (R2 = 0.08, p < 0.0001) and formation parameters (R2 = 0.17, p < 0.0001). This study supports the overall efficacy of antiresorptive therapies in terms of reducing bone remodeling, improving bone density, and pain in FD.

Allogeneic Cell Therapy Applications in Neonates: A Systematic Review.

Neonatal cell therapy applications are increasing; however, data on allogeneic cell therapy are limited. To summarize evidence on allogeneic cell therapy in term and preterm neonates. Cochrane Central Register of Controlled Trials, Embase, Ovid Medline, and various registries were searched for studies investigating the safety, feasibility, and efficacy of allogeneic cell therapy in neonates. Two authors independently selected the articles, extracted data, and assessed the risk of bias. Twelve published (153 infants) and 21 ongoing studies were included. These studies predominantly sourced allogeneic cells from umbilical cord blood (UCB). Mesenchymal stromal cells (MSCs) were the main cell type used (134 of 153 infants); others included UCB-derived total nucleated cells (TNCs) and human amnion epithelial cells (hAECs). Applications included bronchopulmonary dysplasia (BPD; 113 infants), Krabbe disease (13 infants), intraventricular haemorrhage (10 infants), perinatal arterial ischemic stroke (10 infants), hypoxic-ischaemic encephalopathy (6 infants), and necrotizing enterocolitis (1 infant). Nine out of 12 studies did not report any serious adverse events (SAEs) related to cell administration. Three studies reported SAEs, such as graft versus host disease (GVHD) in 5 infants (UCB-derived TNCs for Krabbe disease); and transient cardiorespiratory compromise in 1 infant (hAECs for BPD). Data on efficacy outcomes were limited. The safety and feasibility of allogeneic cell therapy applications in neonates are available, mainly from the use of MSCs. Further safety data for other cell types are required, and the risk of GVHD in different settings needs to be determined. Efficacy studies are largely lacking for all cell types. The protocol was registered with PROSPERO (registration number CRD42023397876), the international prospective register for systematic reviews (https://www.crd.york.ac.uk/PROSPERO).

The effects of low-level laser therapy and photodynamic therapy on oral health of fixed orthodontics patients. A systematic review and meta-analysis

Objective To investigate the effect of low-level laser and photodynamic therapy on the oral health, and periodontal tissue of fixed orthodontic patients and the effect of using photobiomodulation methods compared to routine plaque removal methods and the amount of plaque in fixed orthodontic patients.Method and materials First, the title and summary of related articles were collected by using the search strategy electronic databases PUBMED, EMBASE, Cochrane's CENTRAL, Scopus, ISI and all the articles that were published from the beginning to February 2023 were evaluated. The title, abstracts and full texts of all the relevant studies were reviewed respectively, and those meeting the criteria were entered into our study. Finally, the quality of the studies was examined and the results of the studies were pooled by means of random effects inverse variance meta-analysis.Results Eighteen randomized studies, conducted between 2015 and December 2022, were selected for meta-analysis. Five studies were conducted as split-mouth, twelve as parallel-group, and one as a cross-over design. Among the studies, five examined the effects of low-level laser therapy and twelve assessed the effects of photodynamic therapy. The meta-analysis revealed that photodynamic therapy significantly reduced probing depth compared to scaling (MD=-0.2 mm, P<0.001), though the difference does not seem to be clinically significant. But no significant differences between photodynamic therapy and scaling or low-level laser therapy and control groups in terms of plaque index, or bleeding on probing, gingival crevicular fluid volume, gingival recession, clinical attachment loss, bacterial load and concentrations of inflammatory substances across multiple follow-up periods.Conclusion Moderate evidence indicates that photodynamic therapy (PDT) is comparable to conventional methods in improving oral health, as measured by periodontal indices, inflammatory proteins, bacterial colonies, and white spot lesions, making it a suitable alternative. Limited evidence suggests low-level laser therapy (LLLT) may improve oral health, particularly addressing caries, but further research is needed.

Trajectories of depression symptoms, anxiety symptoms and functional impairment during internet-enabled cognitive-behavioural therapy

Underlying classes capture differences between patient symptom trajectories during psychological therapy. This has not been explored for one-to-one internet-delivered therapy or functional impairment trajectories.Patients experiencing depression or anxiety received cognitive-behavioural therapy with a therapist using an online chat platform (N = 52,029). Trajectory classes of depression symptoms (PHQ9), anxiety symptoms (GAD7) and functional impairment (WSAS) were investigated using growth mixture modelling. Multinomial regressions tested associations between baseline variables and trajectory class.A four-class trajectory model was selected for each outcome, and these were highly similar. Each outcome showed three classes with initially moderate-severe symptoms or impairment: one demonstrated no change, one gradual improvement and one fast improvement. A fourth class had mild baseline scores and minimal improvement. In the moderate-severe classes, patients in the two with improvement were more likely to be employed and not to have obsessive-compulsive disorder. Fast improvement was likelier than gradual improvement or no change for patients with older age, no disability (e.g., physical, learning), or lower comorbid symptom or impairment scores. Associations with functional impairment classes were more similar to associations with depression classes than anxiety classes. Results were largely consistent with findings from face-to-face therapy. This study is an important step towards personalising therapy in terms of suitability and continuation.

Implementing precision oncology for sarcoma patients: the CCCLMUmolecular tumor board experience

PurposeDue to poor outcomes and limited treatment options, patients with advanced bone and soft tissue sarcomas (BS/STS) may undergo comprehensive molecular profiling of tumor samples to identify possible therapeutic targets. The aim of this study was to determine the impact of routine molecular profiling in the setting of a dedicated precision oncology program in patients with BS/STS in a German large-volume sarcoma center.Methods92 BS/STS patients who received comprehensive genomic profiling (CGP) and were subsequently discussed in our molecular tumor board (MTB) between 2016 and 2022 were included. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings was analyzed.Results89.1% of patients had received at least one treatment line before NGS testing. At least one molecular alteration was found in 71 patients (82.6%). The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each). Druggable alterations were identified, and treatment recommended in 32 patients (37.2%). Of those patients with actionable alterations, ten patients (31.2%) received personalized treatment and six patients did benefit from molecular-based therapy in terms of a progression-free survival ratio (PFSr) > 1.3.ConclusionOur single-center experience shows an increasing uptake of next-generation sequencing (NGS) and highlights current challenges of implementing precision oncology in the management of patients with BS/STS. A relevant number of patients were diagnosed with clinically actionable alterations. Our results highlight the potential benefit of NGS in patients with rare cancers and currently limited therapeutic options.

Improving Home-Based Scoliosis Therapy: Findings From a Web-Based Survey.

Conservative scoliosis therapy in the form of assisted physiotherapeutic scoliosis exercises is supplemented by self-contained training at home, depending on the approach (eg, Schroth, the Scientific Exercises Approach to Scoliosis). Complex exercises, lack of awareness of the importance of training, and missing supervision by therapists often lead to uncertainty and reduced motivation, which in turn reduces the success of home-based therapy. Increasing digitalization in the health care sector offers opportunities to close this gap. However, research is needed to analyze the requirements and translate the potential of digital tools into concrete solution concepts. The aim of this study is to evaluate the potential for optimizing home-based scoliosis therapy in terms of motivation, assistive devices, and digital tools. In collaboration with the Institute of Physiotherapy at the Jena University Hospital, a survey was initiated to address patients with scoliosis and physical therapists. A digital questionnaire was created for each target group and distributed via physiotherapies, scoliosis forums, the Bundesverband für Skoliose Selbsthilfe e. V. newsletter via a link, and a quick response code. The survey collected data on demographics, therapy, exercise habits, motivation, assistive devices, and digital tools. Descriptive statistics were used for evaluation. Of 141 survey participants, 72 (51.1%; n=62, 86.1%, female; n=10, 13.9%, male) patients with scoliosis with an average age of 40 (SD 17.08) years and 30 scoliosis therapists completed the respective questionnaires. The analysis of home-based therapy showed that patients with scoliosis exercise less per week (2 times or less; 45/72, 62.5%) than they are recommended to do by therapists (at least 3 times; 53/72, 73.6%). Patients indicated that their motivation could be increased by practicing together with friends and acquaintances (54/72, 75%), a supporting therapy device (48/72, 66.7%), or a digital profile (46/72, 63.9%). The most important assistive devices, which are comparatively rarely used in home-based therapy, included balance boards (20/72, 27.8%), wall bars (23/72, 31.9%), mirrors (36/72, 50%), and long bars (40/72, 55.6%). Therapists saw the greatest benefit of digital tools for scoliosis therapy in increasing motivation (26/30, 87%), improving home therapy (25/30, 83%), monitoring therapy progress (25/30, 83%), and demonstrating exercise instructions (24/30, 80%). In this study, we investigated whether there is any potential for improvement in home-based scoliosis therapy. For this purpose, using online questionnaires, we asked patients with scoliosis and therapists questions about the following topics: exercise habits, outpatient and home-based therapy, motivation, supportive devices, and digital tools. The results showed that a lack of motivation, suitable training equipment, and tools for self-control leads to a low training workload. From the perspective of the patients surveyed, this problem can be addressed through community training with friends or acquaintances, a supportive therapy device, and digital elements, such as apps, with training instructions and user profiles.