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Patients with severe mental disorders in low-resource settings have limited access to services, resulting in overwhelming caregiving burden for families. In extreme cases, this has led to the long-term restraining of patients in their homes. China underwent a nationwide initiative to unlock patients and provide continued treatment. This study aims to quantify household economic burden in families after unlocking and treatment, and to identify factors associated with increased burden due to schizophrenia.
A total of 264 subjects were enrolled from three geographically diverse provinces in 2012. Subjects were patients with schizophrenia who were previously put under restraints and had participated in the ‘unlocking and treatment’ intervention. The primary outcome was the current household economic burden, obtained from past year financial information collected through on-site interview. Patient disease characteristics, treatment, outcomes and family caregiving burden were collected as well. Univariate and multivariate linear regression were used to construct risk factor models for indirect economic burden.
After participating in the intervention, 85% of patients continued to receive mental health services, 70% used medication as prescribed and 80% were never relocked. Family members reported significantly decreased caregiving burden after receiving the intervention. Mean direct and indirect household economic burdens were CNY963 (US$31.7) and CNY11 724 (US$1670) per year, respectively, while family total income was on average CNY12 108 (US$1913) per year. Greater disease severity and poorer patient psychosocial function at time of study were found to be independent factors related to increased indirect burden.
The ‘unlocking and treatment’ intervention has improved the lives of patients and families. Indirect burden due to disease is still a major economic issue that needs to be addressed, potentially through improving treatment and patient functioning. Our findings contribute to the unravelling and eventual elimination of chronic restraining of mentally ill patients in low-resource settings.
Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Introduction: Despite their widespread use, measures of classification accuracy (i.e. sensitivity and specificity) have several limitations that conceals relevant information and may bias decision-making. Assessing the predictive ability of clinical tools instead may provide more useful prognostic information to support decision-making, particularly in an Emergency setting. We sought to contrast classification accuracy versus predictive ability of the Systemic Inflammatory Response Syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA) Sepsis scores for determining mortality risk among patients with infection transported by paramedics. Methods: A one-year cohort of patients with infections transported to the Emergency Department by paramedics was linked to in-hospital administrative databases. Hospital mortality was determined for each patient at the time of discharge. We calculated sensitivity and specificity of SIRS and qSOFA for classifying hospital mortality across different score thresholds, and estimated discrimination (assessed using the C statistic) and calibration (assessed visually) of prediction. Prediction models for hospital mortality were constructed using the aggregated SIRS or qSOFA scores for each patient as a predictor, while accounting for clustering by institution and adjusting for differences in patient age and sex. Predicted and observed risk were plotted to assess calibration and change in risk across levels of each score. Results: A total of 10,409 patients with infection who were transported by paramedics were successfully linked, with an overall mortality rate of 9.2%. The median SIRS score among non-survivors was 2, while the median qSOFA score was 1. SIRS score had higher sensitivity estimates than qSOFA for classifying hospital mortality at all thresholds (0.11 – 0.83 vs. 0.08 – 0.80), but the qSOFA score had better discrimination (C statistic 0.76 vs. 0.71) and calibration. The risk of hospital mortality predicted by the SIRS score ranged from 6.6-24% across score values, whereas the risk predicted by the qSOFA score ranged from 8.6-53%. Conclusion: Assessing the SIRS and qSOFA scores predictive ability reveals that the qSOFA score provides more information to clinicians about a patient's mortality risk despite having worse sensitivity. This study highlights important limitations of classification accuracy for diagnostic test studies and supports a shift toward assessing predictive ability instead. Character count 2490
Although federal regulation of vehicle fuel economy is often seen as environmental policy, over 70% of the estimated benefits of the 2017–2025 federal standards are savings in consumer expenditures on gasoline. Rational-choice economists question the counting of these benefits since studies show that the fuel efficiency of a car is reflected in its price at sale and resale. We contribute to this debate by exploring why most consumers in the United States do not purchase a proven fuel-saving innovation: the hybrid-electric vehicle (HEV). A database of 110 vehicle pairs is assembled where a consumer can choose a hybrid or gasoline version of virtually the same vehicle. Few choose the HEV. A total cost of ownership model is used to estimate payback periods for the price premiums associated with the HEV choice. In a majority of cases, a rational-choice explanation is sufficient to understand consumer disinterest in the HEV. However, in a significant minority of cases, a rational-choice explanation is not readily apparent, even when non-pecuniary attributes (e.g., performance and cargo space) are considered. Future research should examine, from a behavioral economics perspective, why consumers do not choose HEVs when pricing and payback periods appear to be favorable.
Middle-third helical rim defects may arise from trauma or oncological resection, and pose a challenging reconstructive problem. Reconstructing defects larger than 2 cm using traditional methods commits patients to the inconvenience of staged procedures.
This paper describes a single-stage helical rim reconstruction technique using a post-auricular bipedicled flap and ipsilateral conchal cartilage graft for delayed middle-third helical rim reconstruction.
Two examples of this technique used in post-trauma and oncological reconstruction cases are presented, with pre- and post-operative photographs provided for demonstration.
Contralateral graft harvest and staged operations for helical rim reconstruction are associated with donor site morbidity and the inconvenience of multiple operations to achieve the desired reconstructive outcome. Our single-stage helical rim reconstruction technique was well tolerated by patients, and showed satisfactory aesthetic results in terms of size and symmetry.
During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.
The flow of an electrified liquid film down an inclined plane wall is investigated with the focus on coherent structures in the form of travelling waves on the film surface, in particular, single-hump solitary pulses and their interactions. The flow structures are analysed first using a long-wave model, which is valid in the presence of weak inertia, and second using the Stokes equations. For obtuse angles, gravity is destabilising and solitary pulses exist even in the absence of an electric field. For acute angles, spatially non-uniform solutions exist only beyond a critical value of the electric field strength; moreover, solitary-pulse solutions are present only at sufficiently high supercritical electric-field strengths. The electric field increases the amplitude of the pulses, can generate recirculation zones in the humps and alters the far-field decay of the pulse tails from exponential to algebraic with a significant impact on pulse interactions. A weak-interaction theory predicts an infinite sequence of bound-state solutions for non-electrified flow, and a finite set for electrified flow. The existence of single-hump pulse solutions and two-pulse bound states is confirmed for the Stokes equations via boundary-element computations. In addition, the electric field is shown to trigger a switch from absolute to convective instability, thereby regularising the dynamics, and this is confirmed by time-dependent simulations of the long-wave model.
Prenatal programming models have rarely been applied to research on children with prenatal substance exposure, despite evidence suggesting that prenatal drug exposure is a form of stress that impacts neurodevelopmental outcomes and risk for psychopathology. Utilizing data from two longitudinal multisite studies comprising children prenatally exposed to substances as well as a nonexposed comparison group (Maternal Lifestyle Study, n = 1,388; Infant Development, Environment, and Lifestyle study, n = 412), we tested whether early phenotypic indicators of hypothesized programming effects, indexed by growth parameters at birth and infant temperament, served as a link between prenatal substance exposure and internalizing and externalizing behavior at age 5. Latent profile analysis indicated that individual differences in reactivity and regulation for infants prenatally exposed to substances was best characterized by four temperament profiles. These profiles were virtually identical across two independent samples, and demonstrated unique associations with adjustment difficulties nearly 5 years later. Results of path analysis using structural equation modeling also showed that increased prenatal substance exposure was linked to poorer growth parameters at birth, profiles of temperamental reactivity in infancy, and internalizing and externalizing behavior at age 5. This pathway was partially replicated across samples. This study was among the first to link known individual-level correlates of prenatal substance exposure into a specific pathway to childhood problem behavior. Implications for the developmental origins of a child's susceptibility to psychopathology as a result of intrauterine substance exposure are discussed.