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Objectives There is a paucity of research on the impact of cancer treatment on the health-related quality of life (HRQOL) of adolescent and young adult (AYA) patients with cancer. Patient-reported outcomes (PROs) are self-report measures used to assess HRQOL and symptom burden. The extent to which PROs have been included in trials that include common AYA cancer types has not been previously assessed. Methods Therapeutic phase 3 trials among common AYA cancer types (Hodgkin lymphoma, non-Hodgkin lymphoma, acute lymphoblastic leukemia, sarcomas, and germ cell tumors) initiated between 2007 and 2020 were identified on ClinicalTrials.gov . The proportions and characteristics of trials including a PRO endpoint were assessed. For comparison with an older population, the proportion of breast and colorectal therapeutic phase 3 trials including PRO endpoints were assessed. Results Eighty-seven studies met the inclusion criteria. Overall, 20.7% of therapeutic phase 3 AYA trials included a PRO endpoint, and only one trial published PRO data. Germ cell tumors (42.9%) and non-Hodgkin lymphoma (40%) trials had the highest proportions of PRO inclusion. The European Organization for Research and Treatment of Cancer generic, cancer-specific quality of life questionnaire was the most commonly used PRO measure; nevertheless, the measures used varied within and between cancer types. The proportion of trials including a PRO endpoint did not change significantly between 2007 to 2013 and 2014 to 2020 (18.6% vs 22.7%, P=.79). Conclusions Few therapeutic phase 3 AYA cancer trials include PRO endpoints, fewer publish PRO data, and there is no homogeneity in the measures administered. Therapeutic trials represent an underused opportunity to capture PRO data in the AYA population with the goal of improving HRQOL outcomes.

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO2/FiO2, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

Background Since pediatric cancer drug development is a global enterprise, we sought to provide an overview of the landscape of intercontinental clinical trials in pediatric oncology opened over the last decade. Methods ClinicalTrials.gov was systematically searched to identify all clinical therapeutic trials which opened between 2010 and 2020 and recruited pediatric patients (, Intercontinental collaboration is alarmingly rare in childhood cancer trials, despite the rare disease setting and despite pediatric clinical research being inevitably a global enterprise. Barriers to collaboration should be identified and met with specific solutions to accelerate urgently needed drug development for children and adolescents with cancer.

Background Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which follows the progression of Parkinson's disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the recent description of the disease as well as its first international diagnostic criteria (1996). Method This article proposes a synthesis of the therapeutic trials carried out in DLB in the last 5 years, including PDD patients with DLB patients, using the Clinicaltrials.gov and Pubmed.gov databases. Results We identified 35 therapeutic trials on Clinical Trials and 14 on PubMed. According to our temporal criteria, 21 trials were analyzed. Among the 11 completed trials with reported results, two molecules showed positive results: two trials with zonisamide (phase 2 and 3) showed a gain on parkinsonism and one trial with neflamapimod (phase 2) a gain on cognition and walking. Conclusion In recent years, there has been an increase in the therapeutic research effort in DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, whereas the proportion of positive trials is important. An effective disease modifying would have strong consequences for the patient and the relatives.

Graphical Abstract In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, relatively few clinical trials evaluating iPSC-technology have actually translated into interventional, clinically applied treatment regimens. Herein, our aim was to determine trends in globally conducted clinical trials involving iPSCs. Data were derived both from well-known registries recording clinical trials from across the globe, and databases from individual countries. Comparisons were firstly drawn between observational and interventional studies before the latter was further analyzed in terms of therapeutic and nontherapeutic trials. Our main observations included global distribution, purpose, target size, and types of disorder relevant to evaluated trials. In terms of nontherapeutic trials, the USA conducted the majority, a large average number of participants—187—was included in the trials, and studies on circulatory system disorders comprised a slightly higher proportion of total studies. Conversely, Japan was the frontrunner in terms of conducting therapeutic trials, and the average number of participants was much lower, at roughly 29. Disorders of the circulatory, as well as nervous and visual systems, were all studied in equal measure. This review highlights the impact that iPSC-based cell therapies can have, should development thereof gain more traction. We lastly considered a few companies that are actively utilizing iPSCs in the development of therapies for various diseases, for whom the global trends in clinical trials could become increasingly important. Supplementary Information The online version contains supplementary material available at 10.1007/s12015-021-10262-3.

The therapeutic trial was conducted from December 2018 to May 2019 to compare the therapeutic efficacy of different drug regimens in the treatment of impactive and spasmodic colic in donkeys in Gondar, Northwest Ethiopia. Twenty-five purposively selected donkeys were used in this study. Ten of them were showing suspected clinical signs of impactive colic and the remaining ten were with spasmodic colic. The rest five donkeys were kept as control group. For this trial, each disease category was again grouped into two subgroups. The first sub-group in group A with suspected spasmodic colic was treated with ivermectin and, the second sub-group was treated with fenbendazole. Similarly, the first subgroup in group B with suspected impactive colic was treated with meloxicam and the remaining sub-group was treated with hyoscine butyl bromide. Most vital parameters were recorded before and after treatment of colicky donkeys. Feces and blood samples were collected and examined pre and post-treatment from each donkey. Donkeys treated with ivermectin subcutaneously have 97.3% fecal egg count reduction percentage, whereas donkeys treated with fenbendazole orally have fecal egg count reduction percentage of 79.85%. Donkeys treated with meloxicam, most of the clinical signs disappear within 24 hours of time after treatment. Subcutaneous administration of ivermectin was effective for the treatment of spasmodic colic due to Strongyle infestation in donkeys. Therefore, field veterinarians should practice subcutaneous administration of ivermectin and intramuscular administration of meloxicam for effective treatment of spasmodic and impactive colic in donkeys, respectively.

We presented the case of a 1-month-old girl with diffuse urticarial-like rash since birth. The initial evaluation showed elevated inflammatory markers. The response to treatment helped to narrow the diagnosis. In this case, we explored the differential diagnosis of rashes in this age group and the role of a therapeutic trial of medication as a diagnostic modality.

Background Comprehensive reporting of clinical trials is essential to allow the trial reader to evaluate the methodological rigor of the trial and interpret the results. Since publication of the updated Consolidated Standards of Reporting Trials (CONSORT) guidelines for reporting of parallel clinical trials in humans, extensions for reporting of abstracts and crossover trials have been published. Objectives To describe the types of trials using dogs and cats published from 2015 to 2020 and to evaluate the quality of reporting of a sample of recently published parallel and crossover trials. Animals None. Methods A comprehensive search was conducted to identify parallel or crossover design clinical trials using dogs and cats published from January 1, 2015 onwards. Quality of reporting was evaluated on a subset of trials published during 2019. The reporting of items recommended in the CONSORT reporting guidelines for abstracts, parallel trials, and crossover trials was evaluated independently by 2 reviewers using standardized forms created for this study. Disagreements among reviewers were resolved by consensus. Results were tabulated descriptively. Results The frequency of reporting of trial features varied from low to high. There remain deficiencies in the quality of reporting of key methodological features and information needed to evaluate and interpret trial results. Conclusions and Clinical Importance There is still a need for authors, peer‐reviewers, and editors to follow reporting guidelines such as CONSORT to maximize the value of clinical trials and to increase confidence in the validity of the trial results.

BACKGROUND Atopic dermatitis (AD) is a growing burden in all ages. The aim of this study was to compare trial characteristics between pediatric and adult AD trials. METHODS Data were collected from ClinicalTrials.gov on AD therapeutic trials completed between 2003 and 2019. The trials were classified as pediatrics (mean or median age

Purpose To compare the functional outcomes, knee stability, failure rate and complication rates of combined anterior cruciate ligament (ACL) and anterolateral ligament (ALL) reconstruction with hamstrings grafts between acute and chronic cases. Methods Consecutive patients who underwent combined ACL and ALL reconstruction with hamstrings grafts were evaluated. Patients operated on less than 8 weeks after injury were allocated to group 1, and the others were allocated to group 2. Demographic data, knee stability, and functional outcomes of the 2 groups were evaluated. Results Thirty-four patients in the acute group and 96 in the chronic group were evaluated. The follow-up time was similar between the groups (28.7 ± 5.2 [24-43] months vs 29.4 ± 7.2 [24-58] months; P = 0.696). No differences were found between the groups in age, sex, trauma mechanism, presence of knee hyperextension, graft diameter, and meniscal injuries. There was no difference between the groups in the postoperative KT-1000 and in the pre- or postoperative pivot shift. The preoperative KT-1000 was higher in group 2 (7.9 ± 1.1 vs 7.4 ± 1.2; P = 0.031). There were no differences in the International Knee Documentation Committee or Lysholm. Three (2.3%) patients developed failure, 1 (2.9%) in group 1 and 2 (2.1%) in group 2. The total complication rate was 10% and did not differ between the groups. Conclusions Combined ACL and ALL reconstruction has similar outcomes in patients undergoing surgery in the acute and chronic phases. Patients with chronic injury have similar knee stability, functional scores, and failure rates as acute-injury patients, and patients with acute injury have no more complications than chronic patients. Level of Evidence Level III, retrospective comparative therapeutic trial.

International audience; Background: The availability of effective treatments for psoriasis raises ethical questions about the use of a placebo group in therapeutic trials. We evaluated the use of the placebo over time in such trials.Methods: From trials in a living Cochrane review and network meta-analysis for psoriasis, we included trials comparing a biologic to a placebo or other systemic treatment. First, we tested the changes in placebo rate from 2001 to 2019 by linear regression, then constructed networks for 2004-2019 and evaluated the contribution of the placebo to the network meta-analysis estimates per trial and per comparison.Results: We included 81 trials (36,774 patients). The placebo rate did not decrease significantly over time. The proportion contribution of trials with a placebo decreased from 100% in 2004 to 86% in 2008 and 75% in 2019. However, the proportion contribution of trials without a placebo remained low (from 0% in 2004 to 25% in 2019).Conclusion: The design of future psoriasis trials should be reviewed to improve the number of patients to be included in a placebo group.

COVID‐19 continues to dominate the health‐care burden in the twenty‐first century. While health‐care professionals around the world try their best to minimize the mortality from this pandemic, we also continue to battle the high mortality from different types of cancer. For the hemostasis and thrombosis specialist, these two conditions present some unusual similarities including the high rate of thrombosis and marked elevation of D‐dimers. In this forum article, we discuss these similarities and provide some considerations for future research and therapeutic trials.

Abstract. Identifying the associations between health and personality has been a focus for psychophysiological research. Type D personality is associated with predisposition to physical and psychological ill-health. This statistician-blind parallel-group controlled trial (intervention group vs. waiting list control group) examined the impact of Havening Techniques on the Type D constituents of negative affect (NA) and social inhibition (SI). One hundred twenty-five adult (18+ years) participants in the United Kingdom (72 females, 53 males) completed the Type D Scale-14 (DS14) measure of Type D personality at baseline (T1), 24-hours (T2), and at 1-month (T3). Forty participants in the treatment group received additional stress biomarker assessment of heart rate, blood pressure, and salivary cortisol. Type D caseness remained stable in the waiting list participants ( n = 57). In the treatment group ( n = 68); NA, SI, and total scores decreased from T1 to T2 ( p

Highlights • Pulmonary exacerbation difference is an important clinical trial efficacy endpoint. • Regulators have stressed use of Fuchs criteria-based exacerbation definitions. • We compared criteria-based definitions to investigator assessments of 751 events. • Criteria-based definitions were insensitive, nonspecific, and prone to bias. • An alternative exacerbation definition is needed for future CF drug development., Background Cystic fibrosis (CF) pulmonary exacerbations can be serious respiratory events and reduction in exacerbation rate or risk are important efficacy endpoints for CF therapeutic trials. Variability in exacerbation diagnoses and treatment have led drug developers to employ “objective” exacerbation definitions combining antimicrobial treatment (AT) and the presence of ≥4 of 12 respiratory criteria (first published by Fuchs et al. [NEJM 1994;331(10):637–42]). Assumptions underlying this approach have yet to be formally evaluated. Methods Respiratory events (RE) observed during a 48-week trial of ataluren (NCT02139306), a read-through agent for premature nonsense codons, were compared across six exacerbation definitions: any AT, intravenous AT (IVAT), ≥4 Fuchs criteria present, AT plus ≥4 Fuchs criteria, IVAT plus ≥4 Fuchs criteria, and investigator assessment. Fuchs definitions were evaluated by assessing missingness of individual criteria and associations between criteria presence and clinician exacerbation assessment. Results Among 751 RE, more than one third had ≥4 Fuchs criteria present but were not assessed as exacerbations by investigators. Data for ≥1 and for 4 Fuchs criteria, respectively, were missing for ~ 90% and >30% of RE. Only 6/12 Fuchs criteria were present more often when investigators assessed RE as exacerbations than when they did not. Conclusions “Objective” definitions have shortcomings inconsistent with their purpose of optimizing exacerbation capture in clinical trials : 1) they capture events clinicians do not consider exacerbations, 2) are prone to data missingness which can bias the likelihood of meeting the definition, and 3) employ criteria that are not associated with investigator assessment of exacerbation.

X-linked retinoschisis (XLRS) is an inherited retinal condition that leads to schisis of the retina. In the past, treatment trials for XLRS have generally used OCT monitoring of the schitic cavities as the primary structural outcome measure and best corrected visual acuity as the primary functional outcome. Here, we report two cases of genetically confirmed XLRS with marked fluctuations in OCT morphology in the absence of treatment. Given this demonstration of spontaneous fluctuation in retinal structure on OCT in XLRS we suggest that alternative measures of retinal function should be used in future therapeutic trials in XLRS.

In this review we examine, in the context of the amyloid, tau, and neurodegeneration framework, the available evidence and potential alternatives on how to establish tau positivity (T+) for multiple tau-imaging tracers in order to reach a consensus on normal and abnormal tau imaging values that can be universally implemented in clinical research and therapeutic trials.

Introduction: Perniosis (chilblain) is a highly common, prolonged cold induced skin disorder, a very common nuisance in general skin OPD of northern parts of India where winters are long and prolonged and temperatures dip to almost zero. Various treatment modalities have been tried for its treatment, on time and again but none of the treatments have given optimum fast results. We conducted a study on perniosis in peak winters at one of the tertiary care center of the western India. Aim and Objectives: To study and compare, the efficacy of oral nifedipine v/s topical 5% minoxidil Gel in perniosis. Method: The patients clinically fitting in to the diagnosis of perniosis were divided randomly in to two groups. Necessary clinical examination and investigations were carried out to find out any other associated ailment including pregnancy. Group A was given oral nifedipine 10 mg three times daily and Group B was given topical minoxidil 5% Gel applied twice daily, topically. Irrespective of the group, all the patients were given oral antihistaminics. Both clinical and subjective responses were noted on day 3, 7 and 14, respectively. Results: Out of 84 patients, 30 were males and 54 were females with male to female ratio of 1:1.8. The House wives were affected more among all female patients (51%). In group A and B, 42 cases were included in the study and they completed the follow up till 14th day. In group A, after second week of follow up, 25 cases noted good response, 10 cases explained it as very good and in 6 cases, satisfying response was seen which was statistically significant (p

Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.

PURPOSE: Despite considerable research on the barriers to enrollment in cancer therapeutic trials, few studies have elicited barriers from the perspective of community physicians, who provide the majority of cancer care. The purpose of this study was to characterize barriers to and facilitators of cancer therapeutic trials as perceived by oncologists in community practices. METHODS: Twenty semistructured interviews were conducted with oncologists at six community sites affiliated with City of Hope National Medical Center from March to June 2018. Responses were recorded digitally and transcribed. Data were analyzed using qualitative content analysis. RESULTS: Of the 20 participants, 4 (20%) were women, 13 (65%) had > 10 years of practice experience, and 16 (80%) reported that < 5% of their patients were enrolled in a therapeutic trial. Participants identified four system-level barriers: lack of appropriate trials for community-based settings, insufficient infrastructure support, restrictive eligibility criteria, and financial limitations; three physician-level barriers: lack of awareness of available trials, lack of knowledge of trial details, and lack of time; and two patient-level barriers: patient burden and negative beliefs/attitudes toward research. Efforts aimed to increase trial availability, clinical trial support personnel, and physician knowledge were identified as major facilitators. CONCLUSION: Community oncologists face numerous complex, multifaceted barriers to cancer therapeutic trial enrollment. Although expanding clinical research beyond the academic setting allows access to a larger and more diverse patient population, increasing generalizability and relevance of trial findings, there remains a substantial need for new strategies to improve cancer research delivery in the community.

Patients with Alzheimer's disease (AD) present with both extracellular amyloid-β (Aβ) plaques and intracellular tau-containing neurofibrillary tangles in the brain. For many years, the prevailing view of AD pathogenesis has been that changes in Aβ precipitate the disease process and initiate a deleterious cascade involving tau pathology and neurodegeneration. Beyond this 'triggering' function, it has been typically presumed that Aβ and tau act independently and in the absence of specific interaction. However, accumulating evidence now suggests otherwise and contends that both pathologies have synergistic effects. This could not only help explain negative results from anti-Aβ clinical trials but also suggest that trials directed solely at tau may need to be reconsidered. Here, drawing from extensive human and disease model data, we highlight the latest evidence base pertaining to the complex Aβ-tau interaction and underscore its crucial importance to elucidating disease pathogenesis and the design of next-generation AD therapeutic trials.

Cough is among the most common complaints for which patients worldwide seek medical attention. In a majority of patients with chronic cough (defined as cough of greater than 8 weeks' duration), successful management results from a thorough evaluation and treatment of underlying causes. In a subgroup of patients, however, cough proves refractory to therapeutic trials aimed at known reversible causes of chronic cough. Such patients are appropriately termed as having refractory chronic cough. At present, safe and effective medications are lacking for this challenging patient population. Currently available therapeutic options are usually ineffective or achieve antitussive effect at the expense of intolerable side effects, typically sedation. Fortunately, the past decade has witnessed great progress in elucidating underlying mechanisms of cough. From that knowledge, aided by the development of validated instruments to measure objective and subjective cough-related end points, numerous antitussive drug development programs have emerged. The most active area of inquiry at present involves antagonists of the purinergic P2X receptors. Indeed, four clinical programs (one in Phase 3 and three in Phase 2) are currently underway investigating antagonists of receptors comprised entirely or partially of the P2X3 subunit as potential antitussive medications. Herein we review the foundation on which P2X receptor antagonists were developed as potential antitussive medications and provide an update on current clinical trials.

In modern medicine, natural products have aided humans against their battles with cancer. Among these products, microorganisms, medicinal herbs and marine organisms are considered to be of great benefit. In recent decades, more than 30 fungal immunity proteins have been identified and proved to be extractable from a wide range of fungi, including mushrooms. Although chemotherapy is used to overcome cancer cells, the side effects of this method are of great concern in clinical practice. Fungal products and their derivatives constitute more than 50% of the clinical drugs currently being used globally. Approximately 60% of the clinically approved drugs for cancer treatment have natural roots. Anti-tumor immunotherapy is prospective with a rapidly growing market worldwide due to its high efficiency, immunity, and profit. Polysaccharide extracts from natural sources are being used in clinical and therapeutic trials on cancer patients. This review aims to present the latest findings in cancer treatment through isolated and extraction of fungal derivatives and other natural biomaterials.

Alopecia areata (AA) is lost hair from a few or all regions of the body, for the most part from the scalp. Etiology and pathogenesis of alopecia areata being not totally comprehended, is accepted to be multifactorial in ancestry. Recently, studies suggested an association between alopecia and types of viruses, therefore we concerned to investigate the association between CMV infection and alopecia areata. This study included of 100 individuals (50 alopecia patients and 50 healthy). Mean age of study groups were 20.90 ± 11.07 and 22.64±12.29 years of cases and control group respectively. Mean of age onset of patients were 20.83 ± 10.0. Out of 50 patients 52{df6391716bcab23f197eab8ba5a452daee5812a1941604c42f67c7803ea6be47} were male, the rest were female. However, 1:1 of control group was male: female. 40{df6391716bcab23f197eab8ba5a452daee5812a1941604c42f67c7803ea6be47} of patients had a positive family history for this disease. Alopecia areata affected on scalp in 78{df6391716bcab23f197eab8ba5a452daee5812a1941604c42f67c7803ea6be47} of cases. All patients had a high concentration of CMV IgM. With treatment of oral ganciclovire drug, a decrease of anti-CMV IgM levels and an increase of CMV IgG levels were observed.

A 33-year-old with a history of endometriosis presented with pain post-orgasm, accompanied by breakthrough bleeding, nausea, sweatiness, and exhaustion. History and examination suggested a gynaecologic component, likely related to the uterus itself. After several therapeutic trials, a clinical response was obtained with the use of a gonadotropin-releasing hormone antagonist, elagolix. The case is discussed with respect to dysorgasmia and post-orgasm illness syndrome. Post-orgasm pain in women has not been well studied, and it is recommended that such periorgasm phenomena be the topic of future research.

Many animal models have been established for respiratory syncytial virus (RSV) infection of infants with the purpose of studying the pathogenesis, immunological response, and pharmaceutical testing and the objective of finding novel therapies and preventive measures. This review centers on a neonatal lamb model of RSV infection that has similarities to RSV infection of infants. It includes a comprehensive description of anatomical and immunological similarities between ovine and human lungs along with comparison of pulmonary changes and immune responses with RSV infection. These features make the newborn lamb an effective model for investigating key aspects of RSV infection in infants. The importance of RSV lamb model application in preclinical therapeutic trials and current updates on new studies with the RSV-infected neonatal lamb are also highlighted.

Neuroinflammation has been implicated in amyotrophic lateral sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, TSPO radioligands have some challenges to overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudo reference analysis technique for 18F-DPA714. Methods: Seven ALS patients from Belgium (58.9 ± 6.7 y old, 5 men and 2 women), 8 healthy volunteers from Belgium (52.1 ± 15.2 y old, 3 men and 5 women), 7 ALS patients from the United States (53.4 ± 9.8 y old, 5 men and 2 women), and 7 healthy volunteers from the United States (54.6 ± 9.6 y old, 4 men and 3 women) from a previously published study underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, Massachusetts) PET/MRI. For 18F-DPA714, maps of total volume of distribution (VT) were compared with SUV ratio (SUVR) images from 40 to 60 min after injection (SUVR40-60) calculated using the pseudo reference regions cerebellum, occipital cortex, and whole brain (WB) without ventricles. For 11C-PBR28, SUVR images from 60 to 90 min after injection using the WB without ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0% ± 5.6%) in primary motor cortices was observed in ALS subjects, as measured by both VT and SUVR40-60 approaches. The highest sensitivity was found for SUVR calculated using the WB without ventricles (average cluster, 21.6% ± 0.1%). 18F-DPA714 VT ratio was highly correlated with the SUVR40-60 (r > 0.8, P < 0.001). A similar pattern of increased uptake (average cluster, 20.5% ± 0.5%) in the primary motor cortices was observed in ALS subjects for 11C-PBR28 SUVR calculated using the WB without ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together resulted in a more extensive pattern of significantly increased glial activation bilaterally in the primary motor cortices. Conclusion: The same pseudo reference region analysis technique for 11C-PBR28 PET can be extended toward 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these 2 tracers enables pooling of TSPO PET data across multiple centers and increases the power of TSPO as a biomarker for future therapeutic trials. ispartof: JOURNAL OF NUCLEAR MEDICINE vol:61 issue:11 pages:1621-1627 ispartof: location:United States status: published

Introduction the aim of this study was to evaluate the correlation among dysphonic and vocal tract discomfort symptoms in patients who underwent empiric therapeutic trial with proton pump inhibitor (PPI) for a suspected laryngopharyngeal reflux (LPR). Materials and methods A total of 34 patients with suspected LPR were enrolled in this study. All of them were evaluated using the reflux finding score, the reflux symptom Index (RSI), the vocal tract discomfort scale (VTDS), and the voice symptom scale (VoiSS) before and after the PPI treatment. Results A significant difference was found between pretreatment and posttreatment reflux finding score, RSI, VTDS, and VoiSS scores. Significant correlations among RSI, VTDS, and VoiSS before the PPI treatment were found. Conclusion PPI treatment determined a significant improvement of symptoms related to dysphonia and vocal tract discomfort in patients with suspected LPR, in addition, significant correlations among the RSI, VTDS, and VoiSS scores were demonstrated thus suggesting that LPR might influence the response of questionnaires not specifically developed in order to assess the complains in LPR patient.

Brachiaria decumbens (signal grass) is a highly productive tropical grass that is widespread in some tropical countries due to its adaptation to a wide range of environments and soil types. However, a limiting factor for the use of this grass is its toxicity from steroidal saponins. Sporadic outbreaks of hepatogenous photosensitization in ruminants grazing on this grass have been reported. Sheep are more susceptible than other animal species and the young are more susceptible than adults. This review article will critically shed light on the B. decumbens profile, its toxic compounds, mechanisms, clinical responses, blood profile alterations, pathological changes, and acute phase responses related to signal grass intoxication. Further research is needed to integrate new findings on B. decumbens intoxication with previous preventive and therapeutic trials to minimize or remove its deleterious toxic effect.

Qualitative and quantitative surveys show that many German general practitioners (GPs) use complementary and alternative medicine (CAM) in their daily work. However, participants in such studies were mostly experienced GPs.The aim of this study was to investigate systematically how young GPs view CAM and to what extent and how they use CAM treatments.Thirteen young physicians in specialist training for general practice as well as GPs who had completed their specialist training within the last 2 years participated in problem-oriented interviews. Interviews were evaluated by qualitative content analysis.The attitudes of participants towards CAM in general and towards specific CAM modalities varied strongly, but doubts regarding a firm evidence base and specific effects over placebo were expressed frequently. Nevertheless, participants were generally open to herbal medicines and all seemed to use them more or less regularly in clinical practice. Other CAM treatments seemed to be used infrequently. Participants used CAM often for minor illnesses; largely as a first low-intensity therapeutic trial to avoid potentially harmful conventional treatments; and to comply with patient preferences.Compared to more experienced GPs, the participants in our study tended to be more critical towards CAM. Apart from herbal medicines, CAM treatments were used rarely.Hintergrund: Quantitative und qualitative Studien haben gezeigt, dass viele deutsche Allgemeinmediziner*innen komplementär- und alternativmedizinischen Verfahren (KAV) in ihrer täglichen Arbeit verwenden. Diese Studien wurden jedoch primär mit erfahrenen Ärzt*innen durchgeführt. Ziel: Ziel der Studie war es zu untersuchen, wie junge Allgemeinmediziner*innen KAV einschätzen und in welchem Umfang und wie sie solche Verfahren einsetzen. Methoden: Dreizehn Ärzt*innen, die sich in Weiterbildung zum Facharzt für Allgemeinmedizin befanden oder diese maximal vor zwei Jahren abgeschlossen hatten, wurden in problemorientierten Interviews befragt. Die Interviews wurden inhaltsanalytisch qualitativ ausgewertet. Ergebnisse: Die Haltung der Teilnehmer*innen gegenüber KAV im Allgemeinen und gegenüber einzelnen Verfahren variierte stark, aber Zweifel an der Evidenzbasierung und an spezifischen Effekten über Placebo hinaus wurden häufig geäußert. Dennoch waren die Teilnehmer*innen durchgehend offen gegenüber pflanz­lichen Arzneimitteln und verwendeten diese mehr oder weniger regelmäßig in der ärztlichen Routine. Andere KAV schienen aktuell selten verwendet zu werden. Die Teilnehmer*innen setzen KAV häufig bei leichteren Erkrankungen ein, im Sinne eines ersten therapeutischen Versuchs, um nebenwirkungsreichere konventionelle Behandlungen zu vermeiden, und um den Wünschen ihrer Patienten entgegenzukommen. Schlussfolgerung: Im Vergleich zu erfahreneren Allgemeinmediziner*innen waren die Teilnehmer*innen in unserer Studie gegenüber KAV kritischer eingestellt. Abgesehen von pflanzlichen Arzneimitteln wurden KAV nur selten eingesetzt.