Hoffmannacosta1918
The therapeutic potential of medical cannabis to treat a variety of conditions is becoming increasingly recognised. Globally, a large number of countries have now legalised cannabis for medical uses and a substantial number of patients are able to access their medications. Yet in the UK, where medical cannabis was legalised in November 2018, only a handful of NHS prescriptions have been written, meaning that most patients are unable to access the medicine. Reasons for this are manyfold and include the perceived lack of clinical evidence due to the challenges of studying medical cannabis through randomised controlled trials. In order to develop the current evidence base, the importance of incorporating real-world data (RWD) to assess the effectiveness and efficacy of medical cannabis has gradually become recognised. The current paper provides a detailed outline of Project Twenty21 (T21), the UK's first medical cannabis registry, launched in August 2020. We provide the rationale for T21 and describe the methodoal findings complement reports from other large-scale databases globally, indicating that the current RWD is building up a pattern of evidence. With many clinicians demanding better and faster evidence to inform their decisions around prescribing medical cannabis, the current and future results of T21 will expand the existing evidence base on the effectiveness of cannabis-based medical products (CBMPs).
Arginine vasopressin (AVP) is a neuropeptide that modulates both physiological and emotional responses to threat. Until recently, drugs that target vasopressin receptors (V1a) in the human central nervous system were unavailable. The development of a novel V1a receptor antagonist, SRX246, permits the experimental validation of vasopressin's role in the regulation of anxiety and fear in humans.
Here, we examined the effects of SRX246 in a proof-of-concept translational paradigm of fear (phasic response to imminent threat) and anxiety (prolonged response to potential threat).
Healthy volunteers received both SRX246 and placebo in a randomized, double-blind, counter-balanced order separated by a 5-7-day wash-out period. Threat consisted of unpleasant electric shocks. The "NPU" threat test probed startle reactivity during predictable threat (i.e., fear-potentiated startle) and unpredictable threat (i.e., anxiety-potentiated startle).
As predicted, SRX246 decreased anxiety-potentiated startle independent of fear-potentiated startle.
As anxiety-potentiated startle is elevated in anxiety and trauma-associated disorders and decreased by traditional anxiolytics such as SSRIs and benzodiazepines, the V1a receptor is a promising novel treatment target.
As anxiety-potentiated startle is elevated in anxiety and trauma-associated disorders and decreased by traditional anxiolytics such as SSRIs and benzodiazepines, the V1a receptor is a promising novel treatment target.Multiple available combinations of proteasome inhibitors, immunomodulators (IMIDs), and monoclonal antibodies are shifting the relapsed/refractory multiple myeloma (RRMM) treatment landscape. Lack of head-to-head trials of triplet regimens highlights the need for real-world (RW) evidence. We conducted an RW comparative effectiveness analysis of bortezomib (V), carfilzomib (K), ixazomib (I), and daratumumab (D) combined with either lenalidomide or pomalidomide plus dexamethasone (Rd or Pd) in RRMM. A retrospective cohort of patients initiating triplet regimens in line of therapy (LOT) ≥ 2 on/after 1/1/2014 was followed between 1/2007 and 3/2018 in Optum's deidentified US electronic health records database. Time to next treatment (TTNT) was estimated using Kaplan-Meier methods; regimens were compared using covariate-adjusted Cox proportional hazard models. check details Seven hundred forty-one patients (820 patient LOTs) with an Rd backbone (VRd, n = 349; KRd, n = 218; DRd, n = 99; IRd, n = 154) and 348 patients (392 patient LOTs) with a Pd backbone (VPd, n = 52; KPd, n = 146; DPd, n = 149; IPd, n = 45) in LOTs ≥2 were identified. More patients ≥75 years received IRd (39.6%), IPd (37.8%), and VRd (36.7%) than other triplets. link2 More patients receiving VRd/VPd were in LOT2 vs other triplets. Unadjusted median TTNT in LOT ≥ 2 VRd, 13.9; KRd, 8.7; IRd, 11.4; DRd, not estimable (NE); and VPd, 12.0; KPd, 6.7; IPd, 9.5 months; DPd, NE. In covariate-adjusted analysis, only KRd vs DRd was associated with a significantly higher risk of next LOT initiation/death (HR 1.72; P = 0.0142); no Pd triplet was significantly different vs DPd in LOT ≥ 2. Our data highlight important efficacy/effectiveness gaps between results observed in phase 3 clinical trials and those realized in the RW.
To describe magnetic resonance imaging (MRI) findings in professional soccer players with acute apophyseal injury of the hip and to assess their relationship with return to sports.
Adolescent soccer players with diagnosis of apophyseal injury in the anterosuperior and anteroinferior iliac spine were retrospectively evaluated between 2008 and 2016. All athletes underwent hip MRI examination within 4days after onset of clinical complaint. Images were independently analyzed by two radiologists. Medical records were reviewed to obtain clinical data.
Mean displacement of the apophysis was 4.8 ± 4.6mm. Bone edema was present in 82% of athletes and muscular edema in 41%. The mean time to return to sports was 37.3 ± 14.7days. The difference between the measurements of the two radiologists was close to zero with agreement limits below 1.0mm (p < 0.001). There was a significant correlation between displacement of the apophysis and return to sports, as well as between both and the presence of muscular edema. A displacement of the apophysis of 3.0mm might serve as a parameter to predict return to sports/activity before 40days, with a sensitivity of 92% and specificity of 96%, considering conservative physiotherapy treatment.
Displacement of the apophysis and presence of muscular edema evaluated by MRI showed a significant correlation with return to sports in athletes with acute apophyseal injuries of the anterosuperior and anteroinferior iliac spines.
Displacement of the apophysis and presence of muscular edema evaluated by MRI showed a significant correlation with return to sports in athletes with acute apophyseal injuries of the anterosuperior and anteroinferior iliac spines.
In ischemic stroke due to large vessel occlusion (LVO), the indications for patient selection for endovascular mechanical thrombectomy (MT) are based on findings from brain imaging. Several imaging protocols from computed tomography (CT) or magnetic resonance imaging (MRI) are available to guide treatment decisions.
To recommend the optimal choice of imaging modalities and protocols for MT with respect to time windows from symptom onset.
Evaluation of the results of large randomized placebo-controlled trials regarding imaging-based patient selection in MT categorized by time intervals since symptom onset. We discuss methodological aspects, advantages and caveats of individual stroke imaging protocols. Summary of recommendations for the practice.
In MT trials CT was mostly used for patient selection. Plain CT combined with CT angiography or additional perfusion imaging is the preferred option. In early time windows CT with CTA is adequate (≤ 6 h for MT, ≤ 4.5 h in cases of accompanying thrombolysis according to exclusion criteria). In later or unknown time windows perfusion imaging is needed for patient selection. Patients presenting with unknown time windows should be examined by MRI as afirst-line choice in mild to moderate deficits, in cases of severe deficits CT imaging with perfusion imaging.
In MT trials CT was mostly used for patient selection. Plain CT combined with CT angiography or additional perfusion imaging is the preferred option. In early time windows CT with CTA is adequate (≤ 6 h for MT, ≤ 4.5 h in cases of accompanying thrombolysis according to exclusion criteria). In later or unknown time windows perfusion imaging is needed for patient selection. Patients presenting with unknown time windows should be examined by MRI as a first-line choice in mild to moderate deficits, in cases of severe deficits CT imaging with perfusion imaging.
Hybrid necrosis gene Ne1 was delimited into an approximate 4.06 Mb region on chromosome arm 5BL and an InDel marker that co-segregated with Ne1 alleles was developed. Hybrid necrosis in wheat, characterized by progressive chlorosis and necrosis of plant leaves, tillers or whole plants in certain hybrids, is caused by complementary genes Ne1 and Ne2 located on chromosome arms 5BL and 2BS, respectively. Hybrid necrosis can be a barrier in combining desirable traits from various wheat genotypes. In this study, we fine mapped Ne1 on chromosome arm 5BL, and delimited it to a 4.06 Mb region using large segregating recombinant inbred line families from cross 'Zhengnong 17' × 'Yangbaimai'. Genetic characterization confirmed that the ne1 allele was closely associated with a 2.89 Mb deletion in Zhengnong 17. A tightly linked InDel marker, 5B-InDel385, for Ne1 was developed and was used to predict the presence of Ne1 in a diverse panel of 501 common wheat accessions. Among those accessions, 122 (61%) of 200 landraces m cross 'Zhengnong 17' × 'Yangbaimai'. Genetic characterization confirmed that the ne1 allele was closely associated with a 2.89 Mb deletion in Zhengnong 17. A tightly linked InDel marker, 5B-InDel385, for Ne1 was developed and was used to predict the presence of Ne1 in a diverse panel of 501 common wheat accessions. Among those accessions, 122 (61%) of 200 landraces were predicted to carry the Ne1 allele, whereas only 79 (26%) of 301 modern cultivars were predicted to carry Ne1. The significant decrease in Ne1 frequency in modern cultivars indicated that the Ne1 allele had been negatively selected in wheat breeding. This study provides a foundation for marker-assisted selection, gene cloning and functional studies of Ne1 in wheat.
Immunoglobulin G (IgG) subclass 2 deficiency is the most frequent IgG subclass deficiency identified in patients with bronchiectasis, but its clinical significance is not known.
To analyse if bronchiectasis patients with isolated IgG2 deficiency at risk of recurrent exacerbations and/or hospitalisation? Do patients with IgG2 deficiency have worse disease progression?
This is a retrospective study (2015-2020) exploring independent risk factors for recurrent exacerbations (three or more per year) and/or hospitalisation with bronchiectasis exacerbations using multivariable models using binary logistic regression. There was no patient with IgG deficiency, IgG 1, 3 or 4 deficiency, or IgA or IgM deficiency included. In this model, the authors included serum IgG2 level; lung function; body mass index; MRC breathlessness scale; age; sex; number of bronchiectatic lobes; bacterial colonisation; comorbidities; the use of long-term immunosuppressant drugs or antibiotics for more than 28 days. link3 Analysing two-year longitudinal data, one-way ANOVA and Mann-Whitney U test were used to compare bronchiectasis severity between patients with different IgG2 levels.
Serum IgG2 levels (<2.68 g/L, 2.68-3.53 g/L, 3.54-4.45 g/L); hospital admission in the preceding two years; bacterial colonisation with potentially pathogenic organisms and asthma were independent predictors for three or more bronchiectasis exacerbations. Those with low IgG2 levels (<2.68 g/L and 2.68-3.53 g/L), had worsening progression of their bronchiectasis, using the Bronchiectasis Severity Index, over one year compared with those who were IgG2 replete (>4.45 g/L))(p = 0.003, 0.013).
Reduced IgG2 levels was an independent predictor for bronchiectasis exacerbations and have increased disease progression.
Reduced IgG2 levels was an independent predictor for bronchiectasis exacerbations and have increased disease progression.
