Nabilone for the treatment of medication overuse headache: results of a preliminary double-blind, active-controlled, randomized trial.

Medication overuse headache (MOH) is a severe burden to sufferers and its treatment has few evidence-based indications. The aim of this study is to evaluate efficacy and safety of nabilone in reducing pain and frequency of headache, the number of analgesic intake and in increasing the quality of life on patients with long-standing intractable MOH. Thirty MOH patients were enrolled at the University of Modena's Interdepartmental Centre for Research on Headache and Drug Abuse (Italy) in a randomized, double-blind, active-controlled, crossover study comparing nabilone 0.5 mg/day and ibuprofen 400 mg. The patients received each treatment orally for 8 weeks (before nabilone and then ibuprofen or vice versa), with 1 week wash-out between them. Randomization and allocation (ratio 1:1) were carried out by an independent pharmacy through a central computer system. Participants, care givers, and those assessing the outcomes were blinded to treatment sequence. Twenty-six subjects completed the study. Improvements from baseline were observed with both treatments. However, nabilone was more effective than ibuprofen in reducing pain intensity and daily analgesic intake (p < 0.05); moreover, nabilone was the only drug able to reduce the level of medication dependence (-41 %, p < 0.01) and to improve the quality of life (p < 0.05). Side effects were uncommon, mild and disappeared when nabilone was discontinued. This is the first randomized controlled trial demonstrating the benefits of nabilone on headache, analgesic consumption and the quality of life in patients with intractable MOH. This drug also appears to be safe and well-tolerated. Larger scale studies are needed to confirm these preliminary finding

Ability of 3 Frailty Measures to Predict Short-Term Outcomes in Older Patients Admitted for Post-Acute Inpatient Rehabilitation.

OBJECTIVES To evaluate the ability of 3 commonly used frailty measures to predict short-term clinical outcomes in older patients admitted for post-acute inpatient rehabilitation. DESIGN Observational cohort study. SETTING AND PARTICIPANTS Consecutive patients (n = 207) admitted to a geriatric inpatient rehabilitation facility. METHODS Frailty on admission was assessed using a frailty index, the physical frailty phenotype, and the Clinical Frailty Scale (CFS). Predictive capacity of the frailty instruments was analyzed for (1) nonhome discharge, (2) readmission to acute care, (3) functional decline, and (4) prolonged length of stay, using multivariate logistic regression models and receiver operating characteristic (ROC) curves. RESULTS The number of patients classified as frail was 91 (44.0%) with the frailty index, 134 (64.7%) using the frailty phenotype, and 151 (73.0%) with the CFS. The 3 frailty measures revealed acceptable discriminatory accuracy for nonhome discharge (area under the curve ≥ 0.7) but differed in their predictive ability: the adjusted odds ratio (OR) for nonhome discharge was highest for the CFS [6.2, 95% confidence interval (CI) 1.8-21.1], compared to the frailty index (4.1, 95% CI 2.0-8.4) and the frailty phenotype (OR 2.9, 95% CI 1.2-6.6). For the other outcomes, discriminatory accuracy based on ROC tended to be lower and predictive ability varied according to frailty measure. Readmission to acute care from inpatient rehabilitation was predicted by all instruments, most pronounced by the frailty phenotype (OR 5.4, 95% CI 1.6-18.8) and the frailty index (OR 2.5, 95% CI 1.1-5.6), and less so by the CFS (OR 1.4, 95% CI 0.5-3.8). CONCLUSIONS AND IMPLICATIONS Frailty measures may contribute to improved prediction of outcomes in geriatric inpatient rehabilitation. The choice of the instrument may depend on the individual outcome of interest and the corresponding discriminatory ability of the frailty measure

Provider Advice About Pregnancy Weight Gain and Adequacy of Weight Gain

To explore the association between health care provider advice about weight gain and gestational weight gain. Using data from a prospective cohort study, we explored the association between provider advice about weight gain in pregnancy with weight gain adequacy among 1,454 pregnant women. Provider advice was measured by maternal self-report at 27–30 weeks’ gestation. Linear and Poisson regression were used to explore associations. Seventy-eight percent of the women gained outside current recommendations. Fifty-one percent reported receiving weight gain advice from a health care provider. Adjusted Generalized Linear Model (GLM) estimates showed weak effect of provider advice on inadequate or excessive gain (Relative Risk (RR) 0.96, 95% CI 0.74, 1.26 for inadequate gain and RR 1.01, 95% CI 0.97, 1.06 for excessive gain). There is a need for more women to hear about their targeted weight gains during pregnancy and the present advice that exists does little to influence actual gains. Further studies are warranted to find better strategies for providers to motivate their patients to gain weight within the appropriate ranges

Predictive Abilities of the Frailty Phenotype and the Swiss Frailty Network and Repository Frailty Index for Non-Home Discharge and Functional Decline in Hospitalized Geriatric Patients

BACKGROUND: Frailty is increasingly applied as a measure to predict clinical outcomes, but data on the predictive abilities of frailty measures for non-home discharge and functional decline in acutely hospitalized geriatric patients are scarce. OBJECTIVES: The aim of this study was to investigate the predictive ability of the frailty phenotype and a frailty index currently validated as part of the ongoing Swiss Frailty Network and Repository Study based on clinical admission data for non-home discharge and functional decline in acutely hospitalized older patients. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Data were analyzed from 334 consecutive hospitalized patients of a tertiary acute care geriatric inpatient clinic admitted between August 2020 and March 2021. MEASUREMENTS: We assessed frailty using 1) the frailty phenotype and 2) the Swiss Frailty Network and Repository Study (SFNR) frailty index based on routinely available clinical admission data. Predictive abilities of both frailty measures were analyzed for the clinical outcomes of non-home discharge and functional decline using multivariate logistic regression models and receiver operating characteristic curves (ROC). RESULTS: Mean age was 82.8 (SD 7.2) years and 55.4% were women. Overall, 170 (53.1%) were frail based on the frailty phenotype and 220 (65.9%) based on the frailty index. Frail patients based on the frailty phenotype were more likely to be discharged non-home (55 (32.4%) vs. 26 (17.3%); adjusted OR 2.4 (95% CI, 1.4, 5.1)). Similarly, frail patients based on the frailty index were more likely to be discharged non-home compared to non-frail patients (76 (34.6%) vs. 9 (7.9%); adjusted OR, 5.5 (95% CI, 2.6, 11.5)). Both, the frailty phenotype and the frailty index were similarly associated with functional decline (adjusted OR 2.7 (95% CI, 1.5, 4.9); adjusted OR 2.8 (95% CI 1.4, 5.5)). ROC analyses showed best discriminatory accuracy for the frailty index for non-home discharge (area under the curve 0.76). CONCLUSIONS: Frailty using the SFNR-frailty index and the frailty phenotype is a promising measure for prediction of non-home discharge and functional decline in acutely hospitalized geriatric patients. Further study is needed to define the most valid frailty measure

Transcriptional profiling in response to terminal drought stress reveals differential responses along the wheat genome

Background: Water stress during grain filling has a marked effect on grain yield, leading to a reduced endosperm cell number and thus sink capacity to accumulate dry matter. The bread wheat cultivar Chinese Spring (CS), a Chinese Spring terminal deletion line (CS_5AL-10) and the durum wheat cultivar Creso were subjected to transcriptional profiling after exposure to mild and severe drought stress at the grain filling stage to find evidences of differential stress responses associated to different wheat genome regions. Results: The transcriptome analysis of Creso, CS and its deletion line revealed 8,552 non redundant probe sets with different expression levels, mainly due to the comparisons between the two species. The drought treatments modified the expression of 3,056 probe sets. Besides a set of genes showing a similar drought response in Creso and CS, cluster analysis revealed several drought response features that can be associated to the different genomic structure of Creso, CS and CS_5AL-10. Some drought-related genes were expressed at lower level (or not expressed) in Creso (which lacks the D genome) or in the CS_5AL- 10 deletion line compared to CS. The chromosome location of a set of these genes was confirmed by PCR-based mapping on the D genome (or the 5AL-10 region). Many clusters were characterized by different level of expression in Creso, CS and CS_AL-10, suggesting that the different genome organization of the three genotypes may affect plant adaptation to stress. Clusters with similar expression trend were grouped and functional classified to mine the biological mean of their activation or repression. Genes involved in ABA, proline, glycine-betaine and sorbitol pathways were found up-regulated by drought stress. Furthermore, the enhanced expression of a set of transposons and retrotransposons was detected in CS_5AL-10. Conclusion: Bread and durum wheat genotypes were characterized by a different physiological reaction to water stress and by a substantially different molecular response. The genome organization accounted for differences in the expression level of hundreds of genes located on the D genome or controlled by regulators located on the D genome. When a genomic stress (deletion of a chromosomal region) was combined with low water availability, a molecular response based on the activation of transposons and retrotransposons was observed

Short range investigation of sub-micron zirconia particles

The Perturbed Angular Correlations technique was used to determine the nanoconfigurations and their thermal behavior in two non-aggregated zirconia nanospheres of unlike sizes obtained by adding different water amounts during preparation. Three residues containing- Zr surroundings were determined for the non-crystalline starting zirconias, the two organics containing- ones being particle size dependent. Upon crystallization, the nanospheres showed the stabilization of both tetragonal (t´- and t- forms) and cubic (Xc- form) phases. Nevertheless, their amounts, temperature of appearance and thermal evolution depended on the residues containing- precursors. It was observed, in addition, that the structure of the smaller nanospheres became gradually monoclinic. The bigger spheres remained stabilized up to the highest temperatures certainly due to their lower specific surface area that favors the permanence of the oxygen defective t´- form

Retrospective Cohort Study on Acute Care in Obstetrics and Gynecology. Analogies and Differences When Compared to Emergency Medicine

Introduction: the demand for urgent obstetric and gynecology care has progressively increased: in the United States approximately 1.4 million gynecologic visits are made to the emergency department (ED) annually, while almost 75% of women make at least 1 unscheduled visit during pregnancy. Moreover, research has recently focused on setting standards in unscheduled care, and developing quality indicators to improve patients’ health. Therefore, we investigated the characteristics of women with acute gynecological or pregnancy complaints using quality indicators developed for emergency medicine, to better define the needs of this population and improve care. Methods: Retrospective cohort study on ED, and Obstetrics and Gynecology (ObGyn) triage visits, at a tertiary care hospital in Italy, during 2012. Data were analyzed with population-averaged logistic regression and Poisson regression. Results: When compared to the 33,557 ED visits, the 9245 ObGyntriage referrals were more frequently associated with pregnancy (≤12 weeks’ gestation, OR: 30.7, 95%CI; 24.5 - 38.4; &gt;12 weeks’ gestation, OR 81.2, 95%CI; 64.8 - 101.4), vaginal bleeding (OR 156.6, 95%CI; 82.7 - 294.4), diurnal (night access OR 0.87, 95% CI; 0.78 - 0.96) and weekday access (holiday access OR 0.87, 95%CI; 0.78 - 0.95), frequent users (recurrent ED visits IRR 0.87, 95%CI; 0.83 - 0.9) and lower hospital admissions (ED admission OR 1.6, 95%CI; 1.4 - 1.8). Conclusion: ObGyn triage patients differed from ED users, and were at higher risk of “crowding”. Such diversities should be considered to improve female healthcare services and allocate resources more efficiently

Intracellular calcium changes induced by the endozepine triakontatetraneuropeptide in human polymorphonuclear leukocytes: role of protein kinase C and effect of calcium channel blockers

BACKGROUND: The endozepine triakontatetraneuropeptide (TTN) induces intracellular calcium ([Ca(++)](i)) changes followed by activation in human polymorphonuclear leukocytes (PMNs). The present study was undertaken to investigate the role of protein kinase (PK) C in the modulation of the response to TTN by human PMNs, and to examine the pharmacology of TTN-induced Ca(++ )entry through the plasma membrane of these cells. RESULTS: The PKC activator 12-O-tetradecanoylphorbol-13-acetate (PMA) concentration-dependently inhibited TTN-induced [Ca(++)](i )rise, and this effect was reverted by the PKC inhibitors rottlerin (partially) and Ro 32-0432 (completely). PMA also inhibited TTN-induced IL-8 mRNA expression. In the absence of PMA, however, rottlerin (but not Ro 32-0432) per se partially inhibited TTN-induced [Ca(++)](i )rise. The response of [Ca(++)](i )to TTN was also sensitive to mibefradil and flunarizine (T-type Ca(++)-channel blockers), but not to nifedipine, verapamil (L-type) or ω-conotoxin GVIA (N-type). In agreement with this observation, PCR analysis showed the expression in human PMNs of the mRNA for all the α1 subunits of T-type Ca(++ )channels (namely, α1G, α1H, and α1I). CONCLUSIONS: In human PMNs TTN activates PKC-modulated pathways leading to Ca(++ )entry possibly through T-type Ca(++ )channels

Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia

We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30\% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage