A predictive index of intra-dialysis IDH. A statistical clinical data mining approach.

Intra-Dialysis Hypotension (IDH) is one of the main hemodialysis related complications, occurring in 25-30% of the sessions. The factors involved in the onset of hypotension in patients undergoing dialysis are due both to clinical conditions (e.g. presence of vascular or cardiac diseases, neuropathology, anemia) and treatment settings such as temperature of the dialysate, sodium concentration, buffer composition, ultrafiltration rate, etc. The patient’s peculiar reaction to the treatment implies difficulties in preventing IDH episodes. This work explores the possibility to use a multivariate analysis of clinical data to quantify the risk to develop IDH at the beginning of each session. The study is framed in the DialysIS project (Dialysis therapy between Italy and Switzerland) funded by INTERREG – Italy – Switzerland and Co-funded by European Union. Data referring to a total of 516 sessions performed on 70 adult patients undergoing dialysis treatment (50 patients enrolled at A. Manzoni Hospital Lecco, Italy and 20 patients at Regional Hospital of Lugano, Switzerland) were collected. Clinical prescriptions, hydration status, dialysis machine data and hematochemical data were recorded and stored in a unique flexible structured MySQL® database. A statistical analysis was performed to find the potential risk factor related to IDH onset. IDH episodes were automatically detected during the monitored sessions, according to the literature criteria. Patients suffering from IDH in 2 or more sessions were classified as Hypotension Prone (HP), the others as Hypotension Resistant (HR). Initial values of potassium concentration [K+], systolic (SBP) and diastolic (DBP) blood pressure, and weight gain (ΔW) from the end of the previous treatment result to be statistically different between the HP and HR groups. A new index, J, was defined as a weighted patient-specific combination of these parameters and calculated for each session of each patient. The weight of the index coefficients can be dynamically adjourned based on the longitudinal analysis of [K+], SBP, DBP, and ΔW. The results reported in this paper were calculated based on a longitudinal analysis of a minimum of three sessions for each patient. The accuracy of the J index in predicting IDH events has been evaluated and quantified in terms of percentage number of predicted IDH events, with respect to the total number of IDHs. Values of J index higher than 1 point out the risk of IDH onset. J allows the prediction of 100% of IDH episodes using 5 sessions, the 90% using 3 sessions. More specifically, at Lecco Hospital 43 IDH events were detected by the automatic system of which 100% and 95% were respectively predicted by the new index calculated using 5 or 3 sessions. Similarly, at Lugano Hospital 58 IDH were detected by the automatic system of which 100% and 87,5% were predicted using 5 or 3 sessions respectively. A longer longitudinal dataset will allow a higher matching of J to actual IDH episodes. In conclusion, the evaluation of this new index at the beginning of the dialysis session prior to connecting the patient to the machine can provide the clinician with useful information about the risk for the patient to develop cardiovascular instabilities (IDH) during the treatment and can advise the physician about the need to modify the prescription

New Trends in Migraine Pharmacology: Targeting Calcitonin Gene–Related Peptide (CGRP) With Monoclonal Antibodies

Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients’ quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. The demonstrated pivotal role of calcitonin gene-related peptide (CGRP) has fostered the development of CGRP antagonists, unfortunately endowed with liver toxicity, and monoclonal antibodies (mAbs) toward circulating CGRP released during migraine attack or targeting its receptor. Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs. Moreover, in vitro studies are useful to anticipate potential herbal medicine-drug interactions. In particular, they help to elucidate the cellular target (metabolic or transporter protein) and the mechanism (induction or inhibition) by which a single constituent of the herbal medicine acts. The authors highlight the difficulties in predicting herbal–drug interactions from in vitro data where high concentrations of extracts or their constituents are used and pharmacokinetics are missed. Moreover, the difficulty to compare results from human studies where different kinds of herbal extracts are used is discussed. The herbal medicines discussed are among the best sellers and they are reported in the “Herbal Medicines for Human Use” section of the European Medicinal Agency (EMA)

Definition of an index to forecast intradialytic hypotension by a multi-variate statistical analysis

Aim: IntraDialysis Hypotension (IDH) is still one of the main hemodialysis related complications. The patient’s peculiar reaction to the treatment implies difficulties in preventing IDH. This work is aimed at defining an index to quantify the risk of IDH at the beginning of each session through a multivariate analysis of clinical data. Methods: Data referring to 516 sessions performed on 50 patients enrolled at A. Manzoni Hospital Lecco, Italy and 20 patients at Regional Hospital of Lugano, Switzerland were collected. Clinical prescriptions, hydration status, dialysis machine and hematochemical data were recorded and stored in a unique flexible structured database. Patients suffering from IDH in 2 or more sessions were classified as Hypotension Prone (HP), the others as Hypotension Resistant (HR). Statistical analysis was performed to identify the potential risk factor related to IDH onset. A new index, J, was defined as a weighted patient-specific combination of the statistically relevant parameters and calculated for each session of each patient. The weight of the index coefficients can be dynamically adjourned based on the longitudinal analysis of the parameters. J>1 points out the risk of IDH. J prediction accuracy was quantified as the percentage number of predicted IDH events versus the total number of IDHs. Results: Initial values of potassium concentration, systolic and diastolic blood pressure, and weight gain from the end of the previous treatment result to be statistically different between HP and HR patients. J allows recognising the 96% of the IDH episodes. Conclusions: The evaluation of J at the beginning of the dialysis session can provide the clinician useful information about the risk to develop IDH during the treatment and can advise physicians about the need to modify the prescription

Antispasmodic Effect of Bergamot Essential Oil on Rat Isolated Gut Tissues

Preclinical data indicate that bergamot essential oil (BEO) can modulate the synaptic functions within the central nervous system (CNS). Particularly, several data shows that essential oil is endowed with reproducible analgesic and anxiolytic effects that may derived from the ability to modulate the excitatory and inhibitory neurotransmission in the CNS. Although there are differences in the functional complexity of the enteric nervous system (ENS), it is likely that the phytocomplex has biological properties in gut superimposable to those showed in the CNS. Accordingly, the aim of this study was to investigate ex-vivo the effect of bergamot essential oil and its main constituents on the contractile activity of rat isolated colon, jejunum and ileum induced by different muscle stimulants such as acetylcholine (10−6 M) and potassium chloride (80 mM). Our present data demonstrate that BEO inhibits cholinergically- and non cholinergically-mediated contractions in rat isolated gut and that linalool is the most active component. These results suggest that the phytocomplex might be useful in the treatment of spastic disorders in ENS mainly characterized by the presence of pain; incidentally, irritable bowel syndrome (IBS) is a painful condition in which a role for neurotransmitter dysfunction has been envisaged. More investigation is required for clinical translation of the present data

Renal safety of tenofovir in HIV-infected children : a prospective, 96-week longitudinal study

Background: The renal safety of tenofovir in HIV-infected children has not been well studied. In paediatrics, prediction of glomerular filtration rate (GFR) is usually obtained by the Schwartz equation; the Cockcroft-Gault equation is considered more appropriate in children aged >12 years, but can be misleading in younger children. The aims of this study were to assess renal safety and GFR changes as estimated by the Schwartz and Cockcroft-Gault equations in HIV-infected children treated with tenofovir for 96 weeks. Methods: Several parameters of glomerular and tubular function were prospectively assessed (at baseline and at weeks 24, 48, 72 and 96) in 27 HIV-infected children (aged 4.9-18.0 years) receiving a tenofovir-containing antiretroviral regimen. GFR was estimated using Schwartz and Cockcroft-Gault equations in children younger and older than 12 years, respectively. Results: No child experienced a grade 1 (> or =44 micromol/L) or higher increase in serum creatinine or a grade 1 (< or =0.71 mmol/L) or higher hypophosphataemia. Serum bicarbonate values were in the normal range for age at baseline. Mean serum creatinine, serum phosphorus and serum bicarbonate values remained unchanged. No child showed proteinuria, microalbuminuria or glycosuria at baseline or during the study period. The mean urinary protein/creatinine, albumin/creatinine, alpha(1)-microglobulin/creatinine and maximal tubular phosphate reabsorption (TmPO(4)/GFR) ratios remained unchanged. Up to week 96, no patient experienced a significant decrease in GFR, as estimated by the more appropriate formula for age. Conclusion: Through 96 weeks, we found no evidence of impaired glomerular or tubular renal function in tenofovir-treated HIV-infected children