EAN consensus statement for management of patients with neurological diseases during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.

The international European Academy of Neurology survey on neurological symptoms in patients with COVID-19 infection.

BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.

Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis.

The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi-DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta-regression. In total, 24 studies were included in the meta-analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow-up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4-30.8] and 65.2% (95% CI, 59.6-70.7), respectively. The corresponding changes in disability score at the last follow-up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0-7.8) and 58.6% (95% CI, 50.3-66.9). Multivariate meta-regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow-up. Reporting of safety data was frequently inconsistent and could not be included in the meta-analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi-DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.

Ketamine does not enhance the quality of recovery following laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Ketamine has been used as part of the multimodal analgesia technique in the acute perioperative period. The effect of perioperative intravenous small-dose ketamine on the quality of recovery from the patient point-of-view has not been assessed. We hypothesized that low-dose ketamine would enhance recovery following laparoscopic cholecystectomy under total intravenous anesthesia. METHODS: One hundred thirty five patients undergoing laparoscopic cholecystectomy were enrolled in this randomized, double-blind placebo-controlled trial. Subjects were randomly assigned to one of three groups: saline, ketamine 0.2 mg/kg, or ketamine 0.4 mg/kg immediately following the induction of anesthesia and before skin incision. The primary endpoint was assessed using the Quality of Recovery Questionnaire (QoR-40), a 40-item quality of recovery scoring system. In addition, early clinical recovery variables, such as time to eye opening, occurrence of nausea and vomiting, pain score, analgesic use, and length of PACU stay were assessed. RESULTS: No differences were detected in the total or individual dimension scores of the QoR-40 questionnaire. The incidence of nausea, vomiting, and other complications did not differ among the three groups. CONCLUSIONS: Small doses of ketamine do not improve the quality of recovery after remifentanil-based anesthesia for laparoscopic cholecystectomy.

Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease.

BACKGROUND: Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS: Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS: Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.

Macroscopic response to microscopic intrinsic noise in three-dimensional Fisher fronts.

We study the dynamics of three-dimensional Fisher fronts in the presence of density fluctuations. To this end we simulate the Fisher equation subject to stochastic internal noise, and study how the front moves and roughens as a function of the number of particles in the system, N. Our results suggest that the macroscopic behavior of the system is driven by the microscopic dynamics at its leading edge where number fluctuations are dominated by rare events. Contrary to naive expectations, the strength of front fluctuations decays extremely slowly as 1/logN, inducing large-scale fluctuations which we find belong to the one-dimensional Kardar-Parisi-Zhang universality class of kinetically rough interfaces. Hence, we find that there is no weak-noise regime for Fisher fronts, even for realistic numbers of particles in macroscopic systems.

Reduced paired pulse depression in the basal ganglia of dystonia patients.

Decreased inhibition and aberrant plasticity are key features in the pathophysiology of dystonia. Impaired short interval cortical inhibition and resultant increased excitability have been described for various forms of dystonia using paired pulse methods with transcranial magnetic stimulation of motor cortex. It is hypothesized that, in addition to cortical abnormalities, impairments in basal ganglia function may lead to dystonia but a deficit of inhibition within the basal ganglia has not been demonstrated to date. To examine the possibility that impaired inhibition and synaptic plasticity within the basal ganglia play a role in dystonia, the present study used a pair of microelectrodes to test paired pulse inhibition in the globus pallidus interna (GPi) and substantia nigra pars reticulata (SNr) of dystonia and PD patients undergoing implantation of deep brain stimulating (DBS) electrodes. We found that there was less paired pulse depression of local field evoked potentials in the basal ganglia output nuclei of dystonia patients compared with Parkinson's disease patients on dopaminergic medication. Paired pulse depression could be restored following focal high frequency stimulation (HFS). These findings suggest that abnormalities exist in synaptic function of striatopallidal and/or striatonigral terminals in dystonia patients and that these abnormalities may contribute to the pathophysiology of dystonia, either independent of, or in addition to the increased excitability and plasticity observed in cortical areas in dystonia patients. These findings also suggest that HFS is capable of enhancing striatopallidal and striatonigral GABA release in basal ganglia output nuclei, indicating a possible mechanism for the therapeutic benefits of DBS in the GPi of dystonia patients.

[Work-related injuries in Monfalcone shipyard (2000-2010)]. / Il fenomeno infortunistico nei lavoratori della cantieristica navale del cantiere di Monfalcone (Gorizia) dal 2000 al 2010.

Shipbuilding industry exhibits higher injury rates at the workplace than those reported in other industrial sectors. Work-related injuries (n = 6714) occurred from 2000 to 2010 at the shipyard of Monfalcone (Gorizia-Italy) were considered. Injury frequency incidence (IF = number of accidents/number of workers x 1000) and injury severity rate were estimated. Among permanent (directly employed) shipyard workers, the IF ranged from 294.6 in 2000 to 113.7 in 2010. Injury severity rates showed the same decreasing trend. The IF for contract workers was unchanged over the calendar period (110.5 in 2000 to 110.9 in 2010) with no significant change in the injury severity rate. These findings suggest an improvement of the working condition for permanent shipyard workers as a result of prevention policies (education and surveillance) and the automation of production processes. Further preventative interventions are suggested to minimize work-related injuries and to promote health and safety in the shipbuilding industry.

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation.

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.

Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson's disease patients.

Parkinson's disease, caused by the loss of dopaminergic nigrostriatal projections, is a debilitating neurodegenerative disease characterized by bradykinesia, rigidity, tremor and postural instability. The dopamine precursor levodopa (L-dopa) is the most effective treatment for the amelioration of Parkinson's disease signs and symptoms, but long-term administration can lead to disabling motor fluctuations and L-dopa -induced dyskinesias (LIDs). Studies in rat striatal slices have shown dopamine to be an essential component of activity-dependent synaptic plasticity at the input to the basal ganglia, but dopamine is also released from ventrally projecting dendrites of the substantia nigra pars compacta (SNc) on the substantia nigra pars reticulata (SNr), a major output structure of the basal ganglia. We characterized synaptic plasticity in the SNr using field potentials evoked with a nearby microelectrode (fEPs), in 18 Parkinson's disease patients undergoing implantation of deep brain stimulating (DBS) electrodes in the subthalamic nucleus (STN). High frequency stimulation (HFS--four trains of 2 s at 100 Hz) in the SNr failed to induce a lasting change in test fEPs (1 Hz) amplitudes in patients OFF medication (decayed to baseline by 160 s). Following oral L-dopa administration, HFS induced a potentiation of the fEP amplitudes (+29.3% of baseline at 160 s following a plateau). Our findings suggest that extrastriatal dopamine modulates activity-dependent synaptic plasticity at basal ganglia output neurons. Dopamine medication state clearly impacts fEP amplitude, and the lasting nature of the increase is reminiscent of LTP-like changes, indicating that aberrant synaptic plasticity may play a role in the pathophysiology of Parkinson's disease.

A randomized controlled double-blind study of rotigotine on neuropsychiatric symptoms in de novo PD.

Management of apathy, depression and anxiety in Parkinson's disease (PD) represents a challenge. Dopamine agonists have been suggested to be effective. This multicenter, randomized (1:1), double-blind study assessed the 6-month effect of rotigotine versus placebo on apathy, depression and anxiety in de novo PD. The primary outcome was the change of apathy, measured with the LARS. The secondary outcomes were the change in depression and anxiety, measured with BDI-2 and STAI-trait and state. Forty-eight drug-naive PD patients were included. The primary outcome was not reached, with a surprisingly high placebo effect on apathy (60%). There was no significant difference in the change of depression at 6 months between rotigotine and placebo. Trait-anxiety was significantly improved by rotigotine compared to placebo (p = 0.04). Compared to placebo, low dose rotigotine significantly improved trait anxiety, but not apathy and depression. The major placebo effect on apathy points towards the importance of a multidisciplinary and tight follow-up in the management of neuropsychiatric symptoms.

Pallidal stimulation in cervical dystonia: clinical implications of acute changes in stimulation parameters.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is successful in dystonia, but the role of each electrical parameters of stimulation is unclear. We studied the clinical effects of acute changes of different parameters of GPi-DBS in cervical dystonia (CD). METHODS: Eight CD patients with bilateral GPi-DBS at 28.6 +/- 19.2 (mean +/- SD) months after surgery were recruited. Mean improvement in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity score was 54.5% compared to before surgery. Ten settings, including a combination of a wide range of pulse widths (PWs), low and high frequencies and voltage, were administered in a randomized double blinded fashion. Clinical benefit was assessed by two raters using the TWSTRS and by the patients using an analogue rating scale. RESULTS: The TWSTRS severity scores were reduced by 56.7% with stimulation at the best settings. Improvement was significantly associated with high frequency (> or = 60 Hz) and high voltage. Stimulation at 130 Hz showed the best clinical improvement. Increasing PWs (from 60 to 450 micros) did not result in a significant improvement. CONCLUSION: Frequency and amplitude appear to be the most important factors in the acute anti-dystonic effects in GPi-DBS patients with CD.

[Genetic analysis (PKD2) of autosomal dominant polycystic kidney disease]. / Análisis genético (PKD2) de la poliquistosis renal autosómica dominante.

Autosomal dominant polycystic kidney disease is a multi-organic hereditary disorder. It is responsible for 7-10% of cases of end stage renal failure. It is caused by mutations in the genes PKD1 and PKD2. Both polycystic kidney disease's forms have a pathogeny and similar clinic, but in the patients with mutation in PKD2, the clinical manifestations appear later and the progression to end stage renal failure happens 10 years later than in the patients with mutation in PKD1. The diagnosis of this disease can be performed through ultrasounds, but the molecular diagnosis offers some advantages, such as the early detection of asymptomatic individuals who carry this genetic defect, in order to perform a preventive monitoring and genetic counselling. In this work, we present the results of the mutational analysis of the PKD2 gene in 18 patients diagnosed with autosomal dominant polycystic kidney disease. The objectives of this work were to analyze the profitability of the genetic study compared with the radiologic study, and perform an early genetic diagnosis in the descendants of patients who were affected by a mutation in the PKD2 gene, trying to establish a correlation between phenotype and genotype. After the genetic analysis, only one family was diagnosed with a mutation in exon 13 of the PKD2 gene (5.56%), which consists on a substitution of the nucleotide adenosine by cytosine (c.2398A>C), which implies that the amino acid methionine is replaced by leucine (p.800Met>Leu). In our population, contrary to what was published in the literature, the mutation of the gene was clinically significant and did segregate with the disease. All the members with a clinical and ultrasound diagnosis of polycystic renal disease presented the above mentioned mutation. We could not confirm any clinical-genetic correlation. Due to the high prevalence of chronic renal failure and terminal chronic renal failure secondary to polycystic kidney disease in our study, an early genetic diagnosis would involve a better prognosis in connection with a closer clinical monitoring.

Battery longevity of neurostimulators in Parkinson disease: A historic cohort study.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor complications in Parkinson disease (PD). Since 2012, the nonrechargeable dual-channel neurostimulator available in France seems to have shorter battery longevity compared to the same manufacturer's previous model. OBJECTIVE: The aim of this study was to evaluate the battery longevity of older and more recent neurostimulators from the same manufacturer and to explore factors associated with battery life variations. MATERIALS AND METHODS: We retrospectively studied our cohort of PD patients who underwent STN DBS between 1987 and 2017. We collected data concerning neurostimulator replacements and parameters. We compared the survival of the first device available, Kinetra® and the current one, Activa-PC® (Medtronic Inc.) and estimated the factors that had an impact on battery longevity through a Cox logistic regression. RESULTS: Three hundred sixty-four PD patients received a total of 654 DBS STN neurostimulators: 317 Kinetra® and 337 Activa-PC®. The survival analysis, using the Kaplan-Meier estimator, showed a difference between the curves of the two devices (log-rank test; p < 0.001). The median survival of an Activa-PC® neurostimulator was 1666 days, while it was 2379 days for a Kinetra®. After adjustment, according to the multivariate analysis, the main factors associated with battery lifetime were: the neurostimulator type; the number of subsequent neurostimulator implantations; the total electrical energy delivered (TEED); and sex. CONCLUSION: The Kinetra® neurostimulator lifetime is 2.5 years longer than the Activa-PC®. The type of the device, the high TEED and the number of subsequent neurostimulator implantations influence battery longevity most. These results have medical-economic implications since the survival of PD patients with DBS increases over years.

Y chromosome microdeletions and alterations of spermatogenesis.

Three different spermatogenesis loci have been mapped on the Y chromosome and named "azoospermia factors" (AZFa, b, and c). Deletions in these regions remove one or more of the candidate genes (DAZ, RBMY, USP9Y, and DBY) and cause severe testiculopathy leading to male infertility. We have reviewed the literature and the most recent advances in Y chromosome mapping, focusing our attention on the correlation between Y chromosome microdeletions and alterations of spermatogenesis. More than 4,800 infertile patients were screened for Y microdeletions and published. Such deletions determine azoospermia more frequently than severe oligozoospermia and involve especially the AZFc region including the DAZ gene family. Overall, the prevalence of Y chromosome microdeletions is 4% in oligozoospermic patients, 14% in idiopathic severely oligozoospermic men, 11% in azoospermic men, and 18% in idiopathic azoospermic subjects. Patient selection criteria appear to substantially influence the prevalence of microdeletions. No clear correlation exists between the size and localization of the deletions and the testicular phenotype. However, it is clear that larger deletions are associated with the most severe testicular damage. Patients with Y chromosome deletions frequently have sperm either in the ejaculate or within the testis and are therefore suitable candidates for assisted reproduction techniques. This possibility raises a number of medical and ethical concerns, since the use of spermatozoa carrying Y chromosome deletions may produce pregnancies, but in such cases the genetic anomaly will invariably be passed on to male offspring.

Intranasal vaccination with poly(lactide-co-glycolide) microparticles containing a peptide T of Ole e 1 prevents mice against sensitization.

BACKGROUND: Biodegradable microparticles, in particular poly(lactide-co-glycolide) (PLGA), have been shown as potential delivery vehicles for intranasal (i.n.) vaccines in animal models. OBJECTIVES: To evaluate whether i.n. administration of PLGA microparticles containing a peptide with the major T cell epitope of Ole e 1, the main allergen of olive pollen, prevented mice from allergic sensitization to the whole protein. METHODS: Peptide-PLGA microparticles were prepared by a solvent evaporation double emulsion method. Microparticles in a size range of 0.8 mum were evaluated for peptide loading and in vitro antigen release. Stability and immunogenicity of the entrapped peptide were retained, as determined by dot blot and ELISA inhibition. BALB/c mice were intranasally treated with peptide-PLGA microparticles for 3 consecutive days, 1 week before sensitization/challenge to Ole e 1. Blood, lungs and spleen were collected and analysed for immune response. Biodistribution of microparticles was investigated using confocal microscopy. RESULTS: I.n. pretreatment of BALB/c mice with peptide-PLGA microparticles before sensitization to Ole e 1 led to a significant inhibition of serum allergen-specific IgE and IgG1 antibody levels, but a marked increase of specific IgG2a antibodies as compared with sham-pretreated mice. Moreover, IL-5 and IL-10 levels in spleen cell cultures were suppressed in peptide-PLGA pretreated mice. The airway histopathologic parameters associated with inflammation were significantly suppressed by the pretreatment. CONCLUSION: These results demonstrate that i.n. immunization with peptide T-PLGA microparticles is effective in preventing subsequent allergic sensitization to Ole e 1. Our data indicate that peptide-PLGA microparticles may be promising candidates for the design of nasal vaccines against allergic diseases in humans.

Delivering a sustainable trauma management training programme tailored for low-resource settings in East, Central and Southern African countries using a cascading course model.

BACKGROUND: Injuries cause five million deaths and 279 Disability Adjusted Life Years (DALYS) each year worldwide. The COSECSA Oxford Orthopaedic Link (COOL) is a multi-country partnership programme that has delivered training in trauma management to nine sub-Saharan countries across a wide-cadre of health-workers using a model of "primary" courses delivered by UK instructors, followed by "cascading" courses led by local faculty. This study examines the impact on knowledge and clinical confidence among health-workers, and compares the performance of "cascading" and "primary" courses delivered in low-resource settings. METHODS: Data was collated from 1030 candidates (119 Clinical Officers, 540 Doctors, 260 Nurses and 111 Medical Students) trained over 28 courses (9 "primary" and 19 "cascading" courses) in nine sub-Saharan countries between 2012 and 2013. Knowledge and clinical confidence of candidates were assessed using pre- and post-course MCQs and confidence matrix rating of clinical scenarios. Changes were measured in relation to co-variants of gender, job roles and primary versus cascading courses. Multivariate regression modelling and cost analysis was performed to examine the impact of primary versus cascading courses on candidates' performance. FINDINGS: There was a significant improvement in knowledge (58% to 77%, p<0.05) and clinical confidence (68% to 90%, p<0.05) post-course. "Non-doctors" demonstrated a greater improvement in knowledge (22%) and confidence (24%) following the course (p<0.05). The degree of improvement of MCQ scores differed significantly, with the cascading courses (21%) outperforming primary courses (15%) (p<0.002). This is further supported by multivariate regression modelling where cascading courses are a strong predictor for improvement in MCQ scores (Coef=4.83, p<0.05). INTERPRETATION: Trauma management training of health-workers plays a pivotal role in tackling the ever-growing trauma burden in Africa. Our study suggests cascading PTC courses may be an effective model in delivering trauma training in low-resource settings, however further studies are required to determine its efficacy in improving clinical competence and retention of knowledge and skills in the long term.

New approach for the strategic control of gastrointestinal nematodes in grazed beef cattle during the growing phase in central Brazil.

We evaluated the effect of different treatment protocols against gastrointestinal nematodes in Nelore beef cattle during the growing phase in the municipality of Terenos, MS, in central Brazil from May 2013 to April 2014 and from May 2014 to April 2015. Ninety-six Nelore calves were kept on Brachiaria brizantha grass during each trial period and were distributed into six experimental groups (replicate paddocks for each group) based on live weight and the number of eggs per gram of feces (EPG): T1 (control)-treated in May, July and September with a saline solution; T2-treated in May and November with 700 µg/kg doramectin; T3-treated in May (doramectin), July (4.7 mg/kg levamisole phosphate) and September (doramectin); T4-treated in May (doramectin), July (200 µg/kg moxidectin) and September (doramectin); T5-treated in May (doramectin), August (levamisole phosphate) and November (doramectin) and T6-treated in May (doramectin), August (moxidectin) and November (doramectin). The calves were weighed and feces were collected (for faecal culture and EPG counts) from calves every 28 days, concomitantly with the collection of forage samples. The efficacies of doramectin, moxidectin and levamisole were low, at 69.2, 65.9 and 69.4% in the first and 13.8, 92.6, and 76.5% in the second experimental periods, respectively, but only the untreated animals lost weight during the dry season. Final weight gains did not differ significantly (p>0.05) among the animals in T2 (120.8 kg), T3 (131.4 kg), T4 (131.2 kg) and T5 (134.4 kg). T6 was the only group with a significantly higher final weight gain (140.9 kg) compared to the protocol with two annual dosages (T2). The weight gain was 31.9% higher in T6 than in the untreated animals (T1). None of the protocols affected the number of larvae on the pasture. Body weight was significantly and negatively (r=-0.65) correlated with EPG counts, which were significantly lower in June (T2, T3, T4 and T6), August (T3), September (T5 and T6), October (T5) and November (T5 and T6). Haemonchus, Cooperia, Trichostrongylus and Oesophagostomum were identified. Treatments in May and November, the most common practice in Brazil, did not increase the final weight gain, so an additional and intermediate treatment during the dry season (August) is recommended.