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Choosing Wisely Canada (CWC) is a national initiative designed to encourage patient-clinician discussions about the appropriate, evidence-based use of medical tests, procedures and treatments. The Canadian Association of Emergency Physicians’ (CAEP) Choosing Wisely Canada (CWC) working group developed and released ten recommendations relevant to Emergency Medicine in June 2015 (items 1–5) and October 2016 (items 6–10). In November 2016, the CAEP CWC working group developed a process for updating the recommendations. This process involves: 1) Using GRADE to evaluate the quality of evidence, 2) reviewing relevant recommendations on an ad hoc basis as new evidence emerges, and 3) reviewing all recommendations every five years. While the full review of the CWC recommendations will be performed in 2020, a number of high-impact studies were published after our initial launch that prompted an ad hoc review of the relevant three of our ten recommendations prior to the full review in 2020. This paper describes the results of the CAEP CWC working group's ad hoc review of three of our ten recommendations in light of recent publications.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Background: To attain the most comprehensive view of the quality of life (QoL) of a child with Duchenne Muscular Dystrophy (DMD), the completion of a pediatric QoL measure by the child and his/her parent and the assessment of QoL and health-related quality of life (HRQoL) as separate constructs is crucial. Previous QoL research has not assessed HRQoL as a separate construct. By using the Quality of My Life (QoML) questionnaire, our objective was to describe QoL and HRQoL in boys with DMD based on child-and parent-reports. Methods: Parent and child dyads identified via the Canadian Neuromuscular Disease Registry received QoML questionnaires (2013-2016). Children and parent-proxy each completed the QoL and HRQoL Visual Analog Scales. Responses were marked on a 10-cm line, with higher scores (max=10) reflecting higher QoL and HRQoL. Descriptive statistics were computed for child- and parent-reports of QoL and HRQoL at three time-points. Results: Mean(SD) QoL and HRQoL scores for child- and parent-reports were: 1) Baseline (n=20 dyads), 8.32(1.72) vs. 6.73(2.23) and 7.63(2.51) vs. 6.73(2.19); 2)18-months (n=10 dyads, n=9 dyads), 7.83(2.05) vs 7.66(1.66) and 7.62(2.41) vs 7.41(2.16); 3) 36-months (n=15 dyads) 7.38(2.00) vs. 6.99(1.77) and 7.19(2.70) vs. 6.76(2.26). Conclusions: Boys with DMD report higher QoL and HRQoL compared to their parents.
Background: Longitudinal data on health-related quality of life (HRQOL) and fatigue in paediatric Duchenne muscular dystrophy (DMD) are limited. Recently, fatigue was reported to be the greatest predictor of poor HRQOL in paediatric DMD. Understanding the trajectory of HRQOL and its relationship with fatigue may facilitate the development of improved therapeutic strategies. Our objective was to describe three-year changes in HRQOL and fatigue in children with DMD. Methods: Patients identified via the Canadian Neuromuscular Disease Registry received mailed questionnaires (2013–2016). HRQOL was assessed using the PedsQLTM GCS and NMM domains, and fatigue was assessed using the MFS domain (patient- and parent-report). Mean three-year change in scores were computed. Pearson correlations were computed between three-year change in HRQOL and fatigue. Results: Mean decline in MFS scores for patient- and parent-reports were 1.03 and 1.19, respectively. Mean decline in GCS scores for patient- and parent-report were 1.75 and 4.13, respectively. Mean change in NMM scores for patient- and parent-report were 0.72 and -8.36, respectively. Change in MFS score was associated with changes in GCS (r=0.72, p<0.001) and NMM scores (r=0.84, p<0.001) by patient-report. Conclusions: Children with DMD experience worse fatigue and HRQOL over time. Parents perceive a greater decline in HRQOL over time compared to patients.
Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group A Streptococcus (GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.
Background: Mowat-Wilson Syndrome (MWS) is a genetic syndrome (ZEB2, OMIM: 235730) that occurs in 1 in 50000 births. It is characterized by microcephaly, intellectual disability, dysmorphisms (prominent chin, cupped ears, broad nasal bridge) and Hirschsprung’s disease. Although motor delay and hypotonia are common components, a myopathy has not been described in MWS literature. A childhood case with myopathic features prompted further study of this rare disease. Methods: Patients were recruited from the Mowat-Wilson Foundation via email or social media to complete a survey. Results: Thirteen surveys were returned to date. Although 54% of the patients reported motor delay, none of the patients had myopathy investigations. The index patient, presented at 1 year old, with hypotonia and developmental delay. Pregnancy and family history were unremarkable. Investigations revealed high CK levels (range 300 to 500 U/L), EMG confirmed myopathic motor units, and muscle biopsy showed type 1 fibre predominance. Single gene sequencing revealed pathogenic mutations of ZEB2, confirming a diagnosis of MWS. Conclusions: The description of myopathic features expands the spectrum of this rare syndrome and adds to the differential diagnosis of hyperCKemia in early childhood.
Background: Fatigue is frequent and disabling in adults with neuromuscular disorders, but not well characterized in paediatric neuromuscular disorders. Recently, fatigue was reported to be associated with poor health-related quality of life in children with Duchenne muscular dystrophy (DMD). Determinants of fatigue—a modifiable symptom—have not been studied in DMD. Our objective was to explore risk factors for fatigue in children with DMD. Methods: Patients aged 4–17 years identified via the Canadian Neuromuscular Disease Registry received mailed questionnaires. Fatigue was assessed using the PedsQLTM Multidimensional Fatigue Scale (patient- and parent-report). Standardized measures for depressive symptoms, sleep disturbances, functional ability and physical activity were used. Spearman’s correlations and Wilcoxon rank-sum tests were computed. Results: Of 194 eligible patients, 64 have responded to date. DMD patients reported greater fatigue than healthy controls from published data. Depressive symptoms were associated with greater fatigue, by patient-report (ρ=-0.44, P<0.001) and parent-report (ρ=-0.40, P=0.002). Sleep disturbances were associated with greater fatigue, by patient-report (ρ=-0.41, P=0.007) and parent-report (ρ=-0.51, P<0.001). Greater functional ability was associated with less fatigue, by parent-report (ρ=0.30, P=0.02). Physical activity and ambulatory status were not associated with fatigue. Conclusions: Fatigue is a significant issue in DMD. Depressive symptoms and sleep disturbances are associated with fatigue, warranting attention in therapeutic strategies to reduce fatigue.
Background: Fatigue was recently reported to be the largest contributor to poor health-related quality of life (HRQOL) in paediatric Duchenne muscular dystrophy (DMD). Additional studies are necessary to confirm the generalizability of this finding. Our objective was to explore the longitudinal relationship between fatigue and HRQOL in an additional cohort of DMD patients. Methods: We performed a secondary analysis of data from a clinical trial (NCT00592553), which enrolled patients with nonsense mutation DMD, aged 5–20 years, from 37 sites in 11 countries (N=174). Fatigue and HRQOL were assessed using the PedsQLTM Multidimensional Fatigue Scale and Generic Core Scales, respectively, by patient- and parent-report at baseline and over 48 weeks. Results: Patients reported greater fatigue than healthy controls from published data. There was no significant difference between patient- and parent-reported fatigue. Fatigue was significantly correlated with worse HRQOL at baseline, by patient-report (r=0.70, P<0.001) and parent-report (r=0.70, P<0.001); and at 48 weeks, by patient-report (r=0.79, P<0.001) and parent-report (r=0.74, P<0.001). Change in fatigue was significantly correlated with change in HRQOL over 48 weeks, by patient-report (r=0.64, P<0.001) and parent-report (r=0.67, P<0.001). Conclusions: Fatigue is a major contributor to HRQOL in DMD. The strong association between fatigue and HRQOL corroborates previous studies, and suggests that reducing fatigue may improve HRQOL.
Choosing Wisely Canada (CWC) is an initiative to encourage patient-physician discussions about the appropriate, evidence based use of medical tests, procedures and treatments. We present the Canadian Association of Emergency Physicians’ (CAEP) top five list of recommendations, and the process undertaken to generate them.
The CAEP Expert Working Group (EWG) generated a candidate list of 52 tests, procedures, and treatments in emergency medicine whose value to care was questioned. This list was distributed to CAEP committee chairs, revised, and then divided and randomly allocated to 107 Canadian emergency physicians (EWG nominated) who voted on each item based on: action-ability, effectiveness, safety, economic burden, and frequency of use. The EWG discussed the items with the highest votes, and generated the recommendations by consensus.
The top five CAEP CWC recommendations are: 1) Don’t order CT head scans in adults and children who have suffered minor head injuries (unless positive for a validated head injury clinical decision rule); 2) Don’t prescribe antibiotics in adults with bronchitis/asthma and children with bronchiolitis; 3) Don’t order lumbosacral spinal imaging in patients with non-traumatic low back pain who have no red flags/pathologic indicators; 4) Don’t order neck radiographs in patients who have a negative examination using the Canadian C-spine rules; and 5) Don’t prescribe antibiotics after incision and drainage of uncomplicated skin abscesses unless extensive cellulitis exists.
The CWC recommendations for emergency medicine were selected using a mixed methods approach. This top 5 list was released at the CAEP Conference in June 2015 and should form the basis for future implementation efforts.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.
The aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the United States of America.
The Kids’ Inpatient Databases (1997–2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. Weighted multivariable logistic regression and chi-square tests were used to evaluate the trends over time and factors associated with hospitalisation, comparing eras before and after publication of the 2003 American Academy of Pediatrics palivizumab immunoprophylaxis guidelines. Secondary outcomes included in-hospital mortality, morbidity, length of stay, and cost.
Overall, 549,265 respiratory syncytial virus-related hospitalisations were evaluated, including 2518 (0.5%) in children with haemodynamically significant heart disease. The incidence of respiratory syncytial virus hospitalisation in children with haemodynamically significant heart disease decreased by 36% when comparing pre- and post-palivizumab guideline eras versus an 8% decline in children without haemodynamically significant heart disease (p<0.001). Children with haemodynamically significant heart disease had higher rates of respiratory syncytial virus-associated mortality (4.9 versus 0.1%, p<0.001) and morbidity (31.5 versus 3.5%, p<0.001) and longer hospital length of stay (17.9 versus 3.9 days, p<0.001) compared with children without haemodynamically significant heart disease. The mean cost of respiratory syncytial virus hospitalisation in 2009 was $58,166 (95% CI:$46,017, $70,315).
These data provide stakeholders with a means to evaluate the cost–utility of various immunoprophylaxis strategies.
A high level of parental involvement is widely considered to be essential for optimal child and adolescent development and wellbeing, including academic success. However, recent consideration has been given to the idea that extremely high levels of parental involvement (often called ‘overparenting’ or ‘helicopter parenting’) might not be beneficial. This study used a newly created overparenting measure, the Locke Parenting Scale (LPS), to investigate the association of overparenting and children's homework. Eight hundred and sixty-six parents completed online questionnaires about their parenting beliefs and intentions, and their attitudes associated with their child's homework. Parents with higher LPS scores tended to take more personal responsibility for the completion of their child's homework than did other parents, and ascribed greater responsibility for homework completion to their child's teacher. However, increased perceived responsibility by parents and teachers was not accompanied by a commensurate reduction in what they perceived was the child's responsibility. Future research should examine whether extreme parental attitudes and reported behaviours translate to validated changes in actual homework support.
Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.
Microcrystals of platinum-group element (PGE)-bearing cobaltite occur in the Gulcari A deposit of vanadiferous titanomagnetite in the lower zone of the Rio Jacaré mafic-ultramafic layered intrusion, Brazil. Aggregates of cobaltite and sperrylite are cluster-like and developed generally along the boundary of Fe-Ti oxide grains with deuteric silicates. Our observations of cryptic zoning, compositional variability and interelement correlations are based on 37 analytical points (wavelength-dispersion spectrometry mode) of cobaltite, and indicate that Ir and Rh behave uniformly with Ni and antipathetically with Co which, in turn, correlates directly with S content. Iridium, Rh and Ni apparently substitute for Co in the As-enriched grain core, and the substitution mechanism invokes solid solution with a cattierite-type molecule: (Ni + Ir + Rh) + (AsS) = Co + (S2). The PGE-bearing cobaltite probably crystallized as a primary phase at 500 to 300°C, from microvolumes of a late fluid phase. The observed enrichment in S and decrease in the As:S ratio at the cobaltite grain margins is a reflection of the increase in sulfur fugacity (fS2) with decrease in temperature of crystallization.
Background: Improvement of health-related quality of life (HRQOL) is a major goal in chronic disease management and HRQOL has become an important outcome in clinical trials. Longitudinal data on HRQOL are needed to elucidate change over time and to assess effectiveness of interventions; such research is lacking in the paediatric Duchenne Muscular Dystrophy (DMD) population. Methods: We followed up participants from our initial HRQOL study in 2013 a year and a half later. Multidimensional generic and disease-specific measures from the Pediatric Quality of Life Inventory were used to assess HRQOL from child and parent perspectives. Mean changes in HRQOL were calculated. Results: Data collection is ongoing and currently, data from 16 families (out of the initial 98) are available. Preliminary results indicated that by both child and parent reports, there were declines in all domains of HRQOL except for social function, in which there was a slight improvement. Mean decline in HRQOL scores ranged from 1.6 to 8.6 for child reports; and 3.3 to 7.7 for parent reports. Conclusion: HRQOL of boys with DMD deteriorates over time. Our results may be helpful in interpreting patient reported outcomes in forthcoming clinical trials and determining minimally clinically important changes in this population.
We investigate the synthesis of kesterite Cu2ZnSnS4 (CZTS) thin films using thermal evaporation from copper, zinc and tin pellets and post-annealing in a sulfur atmosphere. The effects of chemical composition were studied both on the absorber layer properties and on the final solar cell performance. It is confirmed that CZTS thin film chemical composition affects the carrier concentration profile, which then influences the solar cell properties. Solar cells using a CZTS thin film with composition ratio Cu/(Zn+Sn) = 0.87, and Zn/Sn = 1.24 exhibited an open-circuit voltage of 483 mV, a short-circuit current of 14.54 mA/cm2, a fill factor of 37.66 % and a conversion efficiency of 2.64 %. Only a small deviation from the optimal chemical composition can drop device performance to a lower level, which confirms that the CZTS solar cells with high conversion efficiency existed in a relatively narrow composition region.
In my middle fifties, and as a father of young adults who are choosing their paths in life, I find myself looking along my own path. I ask myself why I chose it, where it has taken me, and where it will lead next.
How I Became an Economist: Accidents and Ancestors
Seen from one point of view, my life as an economist is serendipitous, the accidental result of decisions that I made in order to postpone commitments to one career or another. Seen from another point of view, it was no accident that I became a macrofinance economist; perhaps psychological forces have steadily pushed me along a predetermined path.
I grew up in Oxford, England, in an academic family and was fortunate enough to have an intellectually intense education. The private schools I attended, the Dragon School and Winchester College, had their eccentricities but both challenged their students every day. I reached the moment when the English educational system demands that one choose a specialty even earlier than normal, at age fifteen.
Is there a point where parental effort can be too much? While the link between parenting effort and the wellbeing of children has been firmly established, contemporary discussion has proposed that extreme levels of parental protection of and responsiveness to children could be counterproductive. Research has not yet addressed this phenomenon to ascertain if overparenting is a genuinely different type of parenting approach. The purpose of the present study was to gain insight into the parenting actions considered by parenting professionals (psychologists and school guidance counsellors) to be overparenting. One hundred and twenty-eight professionals responded to an online survey about their observations of overparenting, with eighty-six respondents providing lists of the types of actions they believed were behavioural examples of the term. The survey data revealed that certain types of actions were considered to be indicative of overparenting, and that particular beliefs and outcomes may be involved in this parenting approach. Implications for parenting advice and education programs, and further research are discussed.