To determine the tolerability of lamotrigine in elderly patients with epilepsy.
Pooled data from 13 lamotrigine clinical trials.
Multicentre clinical trials conducted in primary care and neurology ...practices.
208 elderly patients (aged > or = 65 years) were identified: 146 lamotrigine-treated patients, 53 carbamazepine-treated patients and 9 phenytoin-treated patients.
Extent of exposure, incidence of drug-related adverse events, serious adverse events and study withdrawals were examined.
The median duration of exposure for lamotrigine monotherapy and add-on therapy was 24.1 and 47.4 weeks, respectively. The median daily dosage of lamotrigine was 100 mg for monotherapy (range 75 to 500 mg) and 300 mg for add-on therapy (range 25 to 700 mg). Overall, the incidence of drug-related adverse events was lower for lamotrigine than comparator drugs: 49% (72/146) for lamotrigine compared with 72% (38/53) for carbamazepine (p = 0.006), and 89% (8/9) for phenytoin (p = 0.035) although patient numbers in each treatment group were not comparable. Patients receiving lamotrigine reported incidences of somnolence (p = 0.012), rash (p = 0.034), and headache (nonsignificant) that were one-half the incidence reported with carbamazepine monotherapy. Rash was the most common reason for study withdrawal: 4% (6/146) lamotrigine, 17% (9/53) carbamazepine and 0% phenytoin. Seven (5%, 7/146) lamotrigine-treated patients, 4 (8%, 4/53) carbamazepine-treated patients and 1 (11%, 1/9) phenytoin-treated patient experienced drug-related serious adverse events.
Lamotrigine, used in the currently prescribed adult dosage regimen, was well tolerated in elderly patients with epilepsy.
Dolowitz et al chart the chronological development of change in civil service reform, health policy and employment policy since 1979, assess the extent of this change, consider whether more change ...occurred in the third term of the Thatcher government and examine the causes of the changes that did occur.
Purpose
We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence ...regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products.
Source
Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv.
Review 1
: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure.
Review 2:
we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology.
Principal findings
No eligible studies included COVID-19 patients.
Review 1:
12 RCTs (
n
= 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk RR, 0.85; 95% confidence interval CI, 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively).
Review 2
: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density.
Conclusions
High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.
ObjectivesSARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, ...particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear.DesignSystematic review.Data sourcesWe searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020.Eligibility criteriaAll comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing.ResultsOf 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified.ConclusionsThere is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.
Background
Pain management for patients in hospital is a major problem. There is significant variation in care provision. Evidence is needed about the ways in which acute pain services are organized ...in order to understand whether these are linked to important differences in patient outcomes. The National Inpatient Pain Study group is a voluntary collaborative venture of inpatient pain specialists in the United Kingdom who are working toward establishing a national prospective database of service provision and activity.
Objectives
The objectives of this article are 1) to describe current pain service provision and activity 2) to define and monitor the quality and side effects of the primary analgesic techniques, such as central neuraxial block or systemic analgesia, and identify variations in practice.
Methods
Phase 1: Surveys were conducted in two phases during 2010–2011. Information about the organization of services was collected from 121 centers via a live Website. Phase 2: The pilot clinical dataset was collected from 13 hospitals in 2011.
Results
Results indicated that staffing varied widely from one to nine nurses per hospital site. Twelve percent of hospitals did not routinely collect data. The main workload was orthopedic and general surgery based on data from 13 hospitals and 29,080 patients in 2011. Thirty‐seven percent of patients reported a pain score of moderate to severe pain on the first assessment by the specialist pain team, and 21% reported severe pain. Nausea and vomiting was the most frequent adverse event reported. Sixty‐nine major adverse events were logged, of which 64 documented respiratory depression (N = 29,080, 0.22%).
Conclusions
Prospective longitudinal data has the potential to improve our understanding of variation in process and outcome measures and establish future research priorities.
Many animal and plant species exhibit increased growth rates, reach larger sizes and, in the cases of crops and farm animals, produce higher yields when bred as hybrids between genetically differing ...strains, a phenomenon known as hybrid vigour or heterosis. Despite the importance of heterosis, and its extensive genetic analysis, little understanding exists of its molecular basis. We aimed to determine whether characteristics of the leaf transcriptome, as an indicator of the innate functional genetic architecture of a plant line, could be used as markers to predict heterosis and the performance of hybrids, a methodology we term Association Transcriptomics. Relationships between transcript abundance of specific genes and the values of heterosis and heterosis-dependent traits were identified and mathematical models were constructed that relate gene expression characteristics in inbred lines of Arabidopsis thaliana and maize with vegetative biomass and grain yield, respectively, in corresponding hybrids. These models were used to predict, using gene expression data, the performance of additional hybrids. The success of the application in a monocot crop of a methodology developed in a dicot model species indicates that transcriptional markers may have widespread applicability in hybrid breeding.
This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues.
The linkage sample of the ...Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test.
According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied.
This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.
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