Effectiveness of a network of automatically activated trained volunteers on the reduction of cardiopulmonary resuscitation manoueuvers initiation time: study protocol.

BACKGROUND: Cardiorespiratory arrest (CRA) is a health emergency with high mortality. Mortality depends on time of initiation and quality of cardiopulmonary resuscitation (CPR) manoeuvres and the use of the automated external defibrillator (AED). METHODS: The aim of the study is to determine the effectiveness of an automatically activated network of volunteers using smartwatch and smartphone applications on the reduction of time of initiation of cardiopulmonary resuscitation manoeuvres. The protocol will be developed in four phases: 1) validation of an application (App) for smartwatch that automatically generates a health alert in case of out-of-hospital cardiorespiratory arrest (OHCA); 2) training course for laypersons on CPR manoeuvres and AED use; 3) creation of a network of volunteers trained in CPR and AED use that covers our city; and 4) simulation in which the network of volunteers is automatically activated via smartphone to attend simulated OHCAs. A total of 134 health alerts will be generated; on 67 occasions the alert will be directed to the emergency health services and to the network of trained volunteers (Intervention Group) and on 67 occasions the alert will be solely directed to the emergency health services (Control Group). The arrival time of the first rescuer, category of first rescuer (emergency services versus network of volunteers), initiation time of manoeuvres and competence will be recorded. DISCUSSION: CPR training for laypersons is advised, especially for relatives and people close to patients with heart disease, to reduce time of initiation of CPR and to improve OHCA survival rates. This study aims to verify that the initiation time of CPR manoeuvres and AED use is shorter in the intervention than in the control group. TRIAL REGISTRATION: Clinicaltrials.gov ID NCT03828305 . Trial registered on February 1, 2019 (retrospective register).

[Altitudinal richness patterns of Papilionidae, Pieridae and Nymphalidae (Lepidoptera) in Mexican mountain areas]. / Patrones de riqueza altitudinal de Papilionidae, Pieridae y Nymphalidae (Lepidoptera: Rhopalocera) en áreas montañosas de México.

Altitudinal richness patterns of Papilionidae, Pieridae and Nymphalidae (Lepidoptera) in Mexican mountain areas. Butterflies constitute an useful group to investigate biodiversity patterns in specific geographic areas. The aim of this study was to describe the altitudinal patterns distribution and to recognize the main grouping factors of these families. We conducted a comparative study between the butterfly fauna (Papilionidae, Pieridae and Nymphalidae) of five Mexican mountain ranges (Sierra de Manantlán, Sierra de Atoyac de Alvarez, Loxicha Region, Teocelo-Xalapa and Sierra de Juárez), that included 34 sites of altitudinal ranges from 100 to 2 820m. Data was obtained from the Zoology Museum of the National University of Mexico, and comprised more than 60 000 butterfly records of 398 taxa (subspecies level) proceeding during the last 35 years. Fauna similarity between localities were analyzed using a cluster analysis by Sorensen similarity coefficient. Species richness showed a general tendency to decrease with altitude; the main difference was found between the locality with higher altitude and the rest of the sites. The principal factors affecting the identified clusters followed this order: the location in Pacific or Atlantic slope, and location on a particular mountain range. Three altitudinal levels (low elevations, up to 1 200m; intermediate elevations, from 1200 to 1800 m; and high elevations, from 1800 to 2500 m) were described in accordance to their main characteristic taxa. While Neartic elements were common in the highest altitudinal floor, Neotropical taxa were common in the lowest one. It was more difficult to characterize the intermediate level in which a high number of localities were clustered; this intermediate level was characterized by the presence of some endemic species. The results suggest that historical factors are preeminent in butterfly fauna composition in these areas. Future studies may include other Mexican mountain areas to obtain more information on the different factors (latitude, altitude, slope) influencing biodiversity patterns.

Comparison of effects of a single dose of MHYOSPHERE® PCV ID with three commercial porcine vaccine associations against Mycoplasma hyopneumoniae (Mhyo) and porcine circovirus type 2 (PCV2) on piglet growth during the nursery period under field conditions.

Pigs routinely undergo stressful vaccination procedures, which are often unavoidable given the unavailability of safer alternatives, challenging animal welfare. The available vaccines for Mycoplasma hyopneumoniae (Mhyo) or Porcine circovirus type 2 (PCV2) are mostly administered intramuscularly in association to prevent Porcine respiratory disease complex (PRDC). MHYOSPHERE® PCV ID is the first vaccine protecting from both agents by intradermal route. This randomized, blind-field trial aimed to compare the effects of MHYOSPHERE® PCV ID with those of three different intramuscular associations of commercially available vaccines. A total of 7072 21-day-old piglets from 12 consecutive batches in one farm were randomly vaccinated with MHYOSPHERE® PCV ID (G1) or Ingelvac CircoFLEX® + Hyogen® (G2), Porcilis® PCV + M + PAC® (G3), and Porcilis® PCV + Hyogen® (G4). Growth performance during the nursery period and adverse reactions (ARs) after vaccine administration were monitored. Average Daily Weight Gain (ADWG) during the first 7 days post-weaning in G1 was 10.92, 3.03, and 20.08 g/day higher than in G2, G3, and G4, respectively, and 0.65, 4.06, and 9.58 g/day higher than in G2, G3, and G4 during the entire nursery period, respectively. G1 ADWG was significantly higher than G4 during both periods and significantly higher than G2 during the first 7 days post-weaning. Incidence of systemic ARs in G2 and G4 was 0.03% and 0.32%, respectively; none were recorded in G1 and G3. Replacing the usual intramuscular vaccination with MHYOSPHERE® PCV ID results in higher growth performance during the first weeks after weaning with no systemic ARs.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part C: use of QSAR and an expert system for the estimation of the mechanism of action of drug-induced hepatobiliary and urinary tract toxicities.

This report describes an in silico methodology to predict off-target pharmacologic activities and plausible mechanisms of action (MOAs) associated with serious and unexpected hepatobiliary and urinary tract adverse effects in human patients. The investigation used a database of 8,316,673 adverse event (AE) reports observed after drugs had been marketed and AEs noted in the published literature that were linked to 2124 chemical structures and 1851 approved clinical indications. The Integrity database of drug patent and literature studies was used to find pharmacologic targets and proposed clinical indications. BioEpisteme QSAR software was used to predict possible molecular targets of drug molecules and Derek for Windows expert system software to predict chemical structural alerts and plausible MOAs for the AEs. AEs were clustered into five types of liver injury: liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, and gall bladder disorders, and six types of urinary tract injury: acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, and urolithiasis. Results showed that drug-related AEs were highly correlated with: (1) known drug class warnings, (2) predicted off-target activities of the drugs, and (3) a specific subset of clinical indications for which the drug may or may not have been prescribed.

Identification of structure-activity relationships for adverse effects of pharmaceuticals in humans: Part B. Use of (Q)SAR systems for early detection of drug-induced hepatobiliary and urinary tract toxicities.

This report describes the development of quantitative structure-activity relationship (QSAR) models for predicting rare drug-induced liver and urinary tract injury in humans based upon a database of post-marketing adverse effects (AEs) linked to approximately 1600 chemical structures. The models are based upon estimated population exposure using AE proportional reporting ratios. Models were constructed for 5 types of liver injury (liver enzyme disorders, cytotoxic injury, cholestasis and jaundice, bile duct disorders, gall bladder disorders) and 6 types of urinary tract injury (acute renal disorders, nephropathies, bladder disorders, kidney function tests, blood in urine, urolithiases). Identical training data sets were configured for 4 QSAR programs (MC4PC, MDL-QSAR, BioEpisteme, and Predictive Data Miner). Model performance was optimized and was shown to be affected by the AE scoring method and the ratio of the number of active to inactive drugs. The best QSAR models exhibited an overall average 92.4% coverage, 86.5% specificity and 39.3% sensitivity. The 4 QSAR programs were demonstrated to be complementary and enhanced performance was obtained by combining predictions from 2 programs (average 78.4% specificity, 56.2% sensitivity). Consensus predictions resulted in better performance as judged by both internal and external validation experiments.

A single-centre, open-label, controlled, randomized clinical trial to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis in a high prevalence area.

The innate immune response acting immediately after initial infection with Leishmania parasites is known to play a relevant role in prevention against clinical progression of the disease. Domperidone is a dopamine D2 receptor antagonist that has shown to enhance the innate cell-mediated immune response. The aim of this study was to assess the preventive efficacy of a domperidone-based treatment programme against clinical canine leishmaniasis (CanL) in a high prevalence area. The study was performed with 90 healthy, seronegative dogs of different sex, age, weight and breed from a single veterinary clinic located in Valencia (Spain). Dogs were randomly allocated into two groups. Dogs in one group (domperidone-treated group; n=44) were administered an oral suspension of domperidone at 0.5 mg/kg bw/day during 30 consecutive days, every 4 months. Dogs in the other group (negative control group; n=46) were left untreated. A 21-month follow-up period was implemented covering two seasonal phases of the sand fly vector. During this period all animals underwent periodic clinical examinations and blood samplings for anti-Leishmania serological testing. Dogs seropositive for Leishmania (IFAT antibody titre≥1:80) plus at least one clinical sign consistent with CanL (indicative of active infection and incipient disease progression) were categorized as a 'prevention failure'. These dogs were withdrawn from the study after confirming the infection by direct observation of the parasite in smears of lymph nodes and/or bone marrow aspirates. The cumulative percentage of 'prevention failure' after 12 months was significantly lower in the domperidone-treated group than in the negative control group (7% versus 35%, p=0.003). Differences between groups persisted after 21 months (11% versus 48%, p<0.001). The prevention rate provided by domperidone was 80% during the first 12 months and 77% throughout the complete 21-month follow-up period, with odds ratios of 7.3 (p=0.001) and 7.15 (p<0.001), respectively, this indicating that the risk for domperidone-treated dogs to develop the clinical disease is quite 7 times lower than for dogs left untreated. The results of this study demonstrate that the implementation of a strategic domperidone-based treatment programme consisting in quarterly repeated 30-day treatments with domperidone effectively reduces the risk to develop clinical CanL in areas with high prevalence of the disease.

Effect of ketoprofen on pre-weaning piglet mortality on commercial farms.

The effect of ketoprofen on pre-weaning piglet mortality was evaluated in a large-scale study on commercial farms. Sows (n= 1486) from 15 farms were included. Half of the sows received 3 mg/kg ketoprofen in a single intramuscular administration within 12 h after farrowing. The other half remained untreated. Pre-weaning mortality was lower in the ketoprofen-treated group than in the control group (8.43% vs. 10.24%, respectively; P= 0.010). The major impact of ketoprofen on mortality was seen between days 2 and 7 postpartum (mortality rates of 2.75% vs. 4.02% for treated and control groups, respectively; P= 0.001). In addition, ketoprofen treatment was associated with a higher number of piglets weaned per litter than when no treatment was given (10.0 vs. 9.84, respectively; P= 0.012).

Use of the nitroblue tetrazolium reduction test for the evaluation of Domperidone effects on the neutrophilic function of healthy dogs.

The nitroblue tetrazolium reduction test (NBT) is an assay based on the activation percentage of neutrophils in peripheral blood, that has been proposed for the follow up of canine leishmaniosis owing to the narrow relationship between the molecules involved in the oxidative burst and the leishmanicidal activity of phagocytes. Domperidone is a drug used for the treatment of canine leishmaniosis having been claimed to stimulate the dogs' cell-mediated immune response. The aim of this study was to evaluate the degree and the lasting of phagocytic activation induced by a 30-day course treatment with Domperidone (0.5 mg/kg/day) in healthy dogs, by using the NBT. A statistically significant increase in the percentages of activated phagocytes was observed in the treated group during treatment, thereafter remaining high for up to one month after the end of treatment. In contrast, untreated dogs maintained the baseline percentage of activated neutrophils all along the study. It is concluded that the NBT is a useful tool for the follow up of the stimulating effects of Domperidone on the neutrophilic response of healthy dogs and that these effects persist for up to one month after treatment with this molecule.