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Despite proven effectiveness in refractory schizophrenia, clozapine remains underutilised, and it is important to understand potential reasons for this. This study’s aim was to examine in a National sample of Consultant Psychiatrists their knowledge of, attitudes and perceived barriers to clozapine use.
Methods:
A novel questionnaire was designed and distributed by email to 275 Consultant Psychiatrists in Republic of Ireland.
Results:
Twenty-eight percent (n = 77) completed the survey, with 55% of respondents practicing for 15 or more years. Clinicians expressed confidence in managing clozapine treatment and side effects and were well aware of clozapine’s clinical effectiveness and guideline-based use. A majority indicated insufficient experience managing rechallenge and half expressed insufficient experience managing adverse events. Perceived patient factors were highlighted as barriers with 69% of respondents reporting patients’ concern about effectiveness and 50% regarding tolerability. Sixty-four percent (n = 40) indicated that a specialised/tertiary clozapine service would facilitate initiation, with 57% (n = 36) reporting less frequent blood monitoring would aid clozapine prescribing. A majority identified that access to dedicated staff (81%, n = 51) and dedicated day hospital services (84%, n = 53) would facilitate community initiation.
Conclusion:
Consultants are familiar with clozapine use and related guidelines. Dedicated staff and facilities for clozapine use is one identified structural change to enhance clozapine prescribing in Ireland. Tertiary service or clinical advice service would assist in clozapine rechallenge cases or in managing significant adverse events. More structured patient education regarding clozapine effectiveness and professional development programmes focused on managing side effects and rechallenge may promote clozapine use.
reSET-O® is an FDA-authorized prescription digital therapeutic (PDT) for opioid use disorder (OUD) providing cognitive behavioral therapy as an adjunct to buprenorphine therapy. This analysis describes differences in inpatient hospitalization rates over a 2-year period between patients treated with the PDT and those who were not.
Methods
A real-world claims analysis using the HealthVerity Private Source 20 database compared inpatient hospitalization rates (including intensive care unit stays and rehospitalizations) in patients who filled a reSET-O prescription (“cases”) to patients not filling their prescription (“controls”). Index date was date of reSET-O initiation for cases, and prescription date for controls, from January 1, 2019 to June 30, 2020. Pre- and post-index incidence rates of HCRU were compared with the incidence rate ratio (IRR) using a repeated-measures negative binomial model, adjusted for age, sex, region, payer type, Charlson comorbidity index (CCI) score, and number of similar services in the 12 months pre-index with an offset for number of days in the 12-month post-index period. Adjusted differences in inpatient hospitalizations in cases vs. controls were evaluated at 3-month intervals beginning at 12 months pre-index through 12 months post-index, using a difference in differences (DID) approach.
Results
In this analysis, 901 cases (median age 36 years, 62.4% female, 73.9% Medicaid recipients, 95% treated with buprenorphine in the post-index period) were compared with 978 controls (median age 38 years, 55.1% female, 65.4% Medicaid recipients, 95% treated with buprenorphine in the post-index period). Incidence rate ratios of inpatient stays trended lower in later pre-post comparison periods among cases (IRRs 0.80, 0.95, 0.87, and 0.75 at 3-, 6-, 9-, and 12 months pre-post, respectively), and trended higher in later pre-post periods in controls (IRRs 0.93, 0.83, 0.86, 0.88 at 3-, 6-, 9-, and 12-month intervals respectively). The DID for controls vs. cases during the 12-month post interval compared to the 12-month pre-index rates, represented a 44% lower incidence of inpatient hospitalizations vs. controls between the first and last quarters of observation.
Conclusions
This difference in difference analysis showed a lower 12-month pre-post incidence rate ratio of inpatient hospitalizations for patients using reSET-O vs. controls, and a 24-month change in quarterly inpatient hospitalizations in reSET-O patients that was almost half that of controls.
The presence of excessive mirror overflow in children with Attention Deficit/Hyperactivity Disorder (ADHD) is discussed in numerous published reports. These reports, however, include a limited age range in their samples. The objective of this study is to examine the effects of diagnosis and sex on mirror overflow and standard deviation (SD) of tap time in children with and without ADHD across a larger age range (5–12 years) of children.
Methods:
One-hundred and forty-eight children with ADHD and 112 age- and sex-matched typically developing (TD) children completed a finger sequencing task. Mirror overflow, SD of tap time, and mean tap time were measured using finger twitch transducers.
Results:
Results reveal a significant diagnostic effect on mirror overflow such that boys and girls with ADHD demonstrate increased overflow compared to same-sex TD children. Boys with ADHD demonstrated more variable tap times compared to TD boys; no diagnostic effect was observed in the girls.
Conclusions:
Boys with ADHD exhibit anomalous motor variability; girls with ADHD show similar levels of variability as TD girls. Boys and girls with ADHD exhibit similar levels of excessive mirror overflow. This lack of sex differences on mirror overflow is distinct from reports finding sex effects on overflow and could result from an examination of a broader age range than is included in prior reports. Adolescent data would provide a greater understanding of the trajectory of anomalous mirror overflow across development. Examination of functional and structural connectivity would expand the current understanding of the neurobiological foundation of motor overflow.
Poor connectivity between diverse resource users and complex wider governance networks is a challenge in environmental governance. Organizations that ‘broker’ interactions among these relationships are expected to improve governance outcomes. Here, we used semi-structured interviews and social network analysis to identify actors in positions to broker coral reef-related information to and from resource users and to assess the performance of these brokers. Representatives (n = 262) of actor groups were interviewed, including local and national government, non-governmental organizations (NGOs), community organizations and resource user groups from 12 communities across four Caribbean countries, to map information-sharing networks and to identify brokers. Broker performance was assessed through separate interviews with coral reef resource users (n = 545). The findings show that marine NGOs were the highest-functioning brokers. Where such local-level organizations were absent, government agencies in reef management roles acted as brokers, but their performance was lower. Actors in brokerage positions did not always effectively share information, with broker performance being positively correlated with network brokerage scores. The results further our understanding of the roles of brokers in different governance contexts. Identifying those in brokerage positions and supporting their roles in connecting local resource users to wider governance networks could encourage functional brokerage and enhance reef management outcomes.
Although researchers have described numerous risk factors for salmonellosis and for infection with specific common serotypes, the drivers of Salmonella serotype diversity among human populations remain poorly understood. In this retrospective observational study, we partition records of serotyped non-typhoidal Salmonella isolates from human clinical specimens reported to CDC national surveillance by demographic, geographic and seasonal characteristics and adapt sample-based rarefaction methods from the field of community ecology to study how Salmonella serotype diversity varied within and among these populations in the USA during 1996–2016. We observed substantially higher serotype richness in children <2 years old than in older children and adults and steadily increasing richness with age among older adults. Whereas seasonal and regional variation in serotype diversity was highest among infants and young children, variation by specimen source was highest in adults. Our findings suggest that the risk for infection from uncommon serotypes is associated with host and environmental factors, particularly among infants, young children and older adults. These populations may have a higher proportion of illness acquired through environmental transmission pathways than published source attribution models estimate.
Guillain Barré syndrome (GBS), which is triggered by autoantibodies produced in response to antigenic stimuli such as certain infections and vaccinations, is the most common cause of acute flaccid paralysis worldwide. Campylobacter, the most common bacterial enteric infection in the USA, is reported to be the most commonly diagnosed antecedent of GBS, yet little information is available about the risk of post-Campylobacter GBS. Data collected through active, population-based surveillance in the Emerging Infections Program during the 2009–2010 novel Influenza A (H1N1) vaccination campaign allowed us to compare confirmed and probable GBS cases to non-cases to determine whether antecedent Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis) was more common among cases and to assess the risk of GBS following Campylobacter infection. We estimate that 8–12% of GBS cases in the USA are attributable to Campylobacter infection (or a diarrhoeal illness consistent with campylobacteriosis), with 434–650 cases of post-diarrhoeal GBS annually and about 49 cases of GBS per 100 000 Campylobacter infections. These results provide updated estimates for post-Campylobacter GBS incidence in the USA and highlight an important benefit of effective measures to prevent Campylobacter infections.
Studies estimating the human health impact of the foodborne disease often include estimates of the number of gastroenteritis hospitalisations. The aims of this study were to examine the degree to which hospital discharge data underreport hospitalisations due to bacterial gastroenteritis and to estimate the frequency of stool sample submission among patients presenting with gastroenteritis. Using linked laboratory and hospital discharge data from a healthcare organisation and its affiliated hospital, we examined the International Classification of Disease (ICD-9-CM) diagnosis codes assigned to hospitalised adults with culture-confirmed Campylobacter, Salmonella, or Escherichia coli O157 infections and determined the frequency of stool sample submission. Among 138 hospitalised patients with culture-confirmed infections, 43% of Campylobacter patients, 56% of Salmonella patients and 35% of E. coli O157 patients had that pathogen-specific code listed on the discharge record. Among patients without their infection listed as a diagnosis, 65% were assigned a nonspecific gastroenteritis code. Submitting a specimen for culture ⩾3 days before discharge was significantly associated with having the pathogen-specific diagnosis listed. Of 6181 patients assigned a nonspecific gastroenteritis code, 69% had submitted a stool sample for bacterial culture. This study can be used to understand differences and adjust for the underreporting and underdiagnosed of Campylobacter, Salmonella and E. coli O157 in hospital discharge and surveillance data, respectively.
The Foodborne Diseases Active Surveillance Network (FoodNet) conducts population-based surveillance for Campylobacter infection. For 2010 through 2015, we compared patients with Campylobacter jejuni with patients with infections caused by other Campylobacter species. Campylobacter coli patients were more often >40 years of age (OR = 1·4), Asian (OR = 2·3), or Black (OR = 1·7), and more likely to live in an urban area (OR = 1·2), report international travel (OR = 1·5), and have infection in autumn or winter (OR = 1·2). Campylobacter upsaliensis patients were more likely female (OR = 1·6), Hispanic (OR = 1·6), have a blood isolate (OR = 2·8), and have an infection in autumn or winter (OR = 1·7). Campylobacter lari patients were more likely to be >40 years of age (OR = 2·9) and have an infection in autumn or winter (OR = 1·7). Campylobacter fetus patients were more likely male (OR = 3·1), hospitalized (OR = 3·5), and have a blood isolate (OR = 44·1). International travel was associated with antimicrobial-resistant C. jejuni (OR = 12·5) and C. coli (OR = 12) infections. Species-level data are useful in understanding epidemiology, sources, and resistance of infections.
The aim of this study was to ascertain farmers’ knowledge of the risk of spread of infection from animals to humans, and their transmission prevention practices. This was a survey of farmers who submitted material to Ireland's Regional Veterinary Laboratories in 2015. There was an 84% response rate (1044 farmers). Ninety per cent of farmers were not aware that infection can be acquired from apparently healthy animals. Over half were not aware that disease could be contracted from sick poultry or pets. Conversely, the knowledge of the risk to pregnant women of infection from birthing animals was high (88%). Four-fifths of farmers sourced drinking water from a private well, and of these, 62% tested their water less frequently than once a year. Of dairy farmers, 39% drank unpasteurised milk once a week or more frequently. Veterinarians were the most commonly cited information source for diseases on farms. The survey findings indicate that the level of farmers’ knowledge and awareness of the spread of infection from animals to humans is a concern. Further education of the farming community is needed to increase awareness of both the potential biohazards present on farms and the practical measures that can be taken to mitigate the risk of zoonoses.
Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.
Methods
Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).
Results
Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.
Conclusions
This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.
Vibrio alginolyticus causes soft tissue and bloodstream infection; little systematically collected clinical and epidemiological information is available. In the USA, V. alginolyticus infections are reported to the Cholera and Other Vibrio Illness Surveillance system. Using data from 1988 to 2012, we categorised infections using specimen source and exposure history, analysed case characteristics, and calculated incidence rates using US Census Bureau data. Most (96%) of the 1331 V. alginolyticus infections were from coastal states. Infections of the skin and ear were most frequent (87%); ear infections occurred more commonly in children, lower extremity infections more commonly in older adults. Most (86%) infections involved water activity. Reported incidence of infections increased 12-fold over the study period, although the extent of diagnostic or surveillance bias is unclear. Prevention efforts should target waterborne transmission in coastal areas and provider education to promote more rapid diagnosis and prevent complications.
Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera epidemics, but other serogroups – such as O75 or O141 – can also produce cholera toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years of surveillance for toxigenic non-O1, non-O139 infections in the United States and map these infections to the state where the exposure probably originated. While serogroups O75 and O141 are closely related pathogens, they differ in how and where they infect people. Oysters were the main vehicle for O75 infection. The vehicles for O141 infection include oysters, clams, and freshwater in lakes and rivers. The patients infected with serogroup O75 who had food traceback information available ate raw oysters from Florida. Patients infected with O141 ate oysters from Florida and clams from New Jersey, and those who only reported being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and Texas. Improving the safety of oysters, specifically, should help prevent future illnesses from these toxigenic strains and similar pathogenic Vibrio species. Post-harvest processing of raw oysters, such as individual quick freezing, heat-cool pasteurization, and high hydrostatic pressurization, should be considered.
Introduction: Hypoglycemia is a common treatment consequence in diabetes mellitus (DM) and the second most common cause of Emergency Department (ED) visits for adverse drug events. Prior studies have examined the rates of ED visits and inpatient hospitalizations for hypoglycemia. These represent only a small proportion of severe hypoglycemic events, as many do not present to hospital. To date, there have been no Canadian population-based studies examining the rates of EMS assist-requiring hypoglycemia in DM patients in the pre-hospital setting. The objective of this study was to determine the prevalence and describe the EMS assist-requiring hypoglycemia in DM patients in Southwestern Ontario. Methods: A population-based retrospective cohort study was conducted on all EMS calls for diabetic emergency from 2008-2014 in Southwestern Ontario, Canada. Data was extracted from the electronic ambulance call records for 11 EMS services in the region. Results: There were 9,265 EMS calls for a diabetic emergency (mean age 59 ± 20 years, 57% male, 82% DM). For 223 calls (2.4%) patients were younger than 19 years of age. The mean blood glucose level on presentation was 2.49 ± 1.02 mmol/L and 2,116 (24%) call subjects had initial GCS score less than 9. Treatment (intravenous glucose or IM glucagon) was given in 7,126 (77%) calls. There were 3,884 (51 %) hypoglycemia episodes with documented insulin use and 1,436 (19 %) documented oral hypoglycemia agents use. Between 2008 and 2014, rates of calls increased by 7.4% (p<0.0001). Prevalence of hypoglycemia calls during the study period was estimated at 189 per 10,000 diabetes patients per year. In 2,297 (24.8%) instances, the patient refused transport to the ED. Conclusion: The rates of EMS assist-requiring hypoglycemia are almost double the rates of hospitalization/ED visits for acute DM complications in our region. Many life threatening episodes of hypoglycemia may go unreported and subsequently not followed by the patient's primary health care provider. Further assessment and proper education following those episodes may help decrease the rate of severe hypoglycemia.
Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy andplacental amino acid transporter gene expression have been associated withdevelopment of the offspring in terms of body composition and bone structure.Several amino acid transporter genes have vitamin D response elements in theirpromoters suggesting the possible linkage of these two mechanisms. We aimed toestablish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levelsrelate to expression of placental amino acid transporters. RNA was extractedfrom 102 placental samples collected in the Southampton Women's Survey,and gene expression was analysed using quantitative real-time PCR. Geneexpression data were normalised to the geometric mean of three housekeepinggenes, and related to maternal factors and childhood body composition. Maternalserum 25(OH)D and VDBP levels were measured by radioimmunoassay. Maternal25(OH)D and VDBP levels were positively associated with placental expression ofspecific genes involved in amino acid transport. Maternal 25(OH)D and VDBPconcentrations were correlated with the expression of specific placental aminoacid transporters, and thus may be involved in the regulation of amino acidtransfer to the fetus. The positive correlation of VDBP levels and placentaltransporter expression suggests that delivery of vitamin D to the placenta maybe important. This exploratory study identifies placental amino acidtransporters which may be altered in response to modifiable maternal factors andprovides a basis for further studies.
We explored the overall impact of foodborne disease caused by seven leading foodborne pathogens in the United States using the disability adjusted life year (DALY). We defined health states for each pathogen (acute illness and sequelae) and estimated the average annual incidence of each health state using data from public health surveillance and previously published estimates from studies in the United States, Canada and Europe. These pathogens caused about 112 000 DALYs annually due to foodborne illnesses acquired in the United States. Non-typhoidal Salmonella (32 900) and Toxoplasma (32 700) caused the most DALYs, followed by Campylobacter (22 500), norovirus (9900), Listeria monocytogenes (8800), Clostridium perfringens (4000), and Escherichia coli O157 (1200). These estimates can be used to prioritize food safety interventions. Future estimates of the burden of foodborne disease in DALYs would be improved by addressing important data gaps and by the development and validation of US-specific disability weights for foodborne diseases.
Although rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2% vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.
US cholera surveillance offers insight into global and domestic trends. Between 2001 and 2011, 111 cases were reported to the Centers for Disease Control and Prevention. Cholera was associated with international travel in 90 (81%) patients and was domestically acquired in 20 (18%) patients; for one patient, information was not available. From January 2001 to October 2010, the 42 (47%) travel-associated cases were associated with travel to Asia. In October 2010, a cholera epidemic started in Haiti, soon spreading to the Dominican Republic (Hispaniola). From then to December 2011, 40 (83%) of the 48 travel-associated cases were associated with travel to Hispaniola. Of 20 patients who acquired cholera domestically, 17 (85%) reported seafood consumption; 10 (59%) ate seafood from the US Gulf Coast. In summary, an increase in travel-associated US cholera cases was associated with epidemic cholera in Hispaniola in 2010–2011. Travel to Asia and consumption of Gulf Coast seafood remained important sources of US cholera cases.
Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 s.d. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not.
Method
A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning.
Results
Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia.
Conclusions
These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment.
In June 2011, a cluster of suspected cases of Guillain–Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May–21 July 2011, exceeding the expected number of cases (n = 1–2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5–∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Design
Longitudinal study.
Setting
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Subjects
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Results
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Conclusions
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.