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Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
This was a naturalistic study of community patients recommended for clozapine treatment.
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
OBJECTIVES/GOALS: Osteoarthritis (OA) is a cartilage destroying disease. We are investigating abaloparatide (ABL) activation of parathyroid hormone receptor type 1 (PTH1R), which is expressed by articular chondrocytes in OA. We propose ABL treatment is chondroprotective in murine PTOA via stimulation of matrix production and inhibition of chondrocyte maturation. METHODS/STUDY POPULATION: 16-week-old C57BL/6 male mice received destabilization of the medial meniscus (DMM) surgery to induce knee PTOA. Beginning 2 weeks post-DMM, 40 Î¼g/kg of ABL (or saline) was administered daily via subcutaneous injection and tissues were harvested after 6 weeks of daily injections and 8 weeks after DMM surgery. Harvested joint tissues were used for histological and molecular assessment of OA using three 5 Î¼m thick sagittal sections from each joint, 50 Î¼m apart, cut from the medial compartment of injured knees. Safranin O/Fast Green tissue staining and immunohistochemistry-based detection of type 10 collagen (Col10) and lubricin (Prg4) was performed using standard methods. Histomorphometric quantification of tibial cartilage area and larger hypertrophic-like cells was performed using the Osteomeasure system. RESULTS/ANTICIPATED RESULTS: Safranin O/Fast Green stained sections showed a decreased cartilage loss in DMM joints from ABL-treated versus saline-treated mice. Histomorphometric analysis of total tibial cartilage area revealed preservation of cartilage tissue on the tibial surface. Immunohistochemical analyses showed that upregulation of Col10 in DMM joints was mitigated in the cartilage of ABL-treated mice, and chondrocyte expression of Prg4 was increased in uncalcified cartilage areas in ABL-treated group. The Prg4 finding suggests a matrix anabolic effect that may counter OA cartilage loss. Quantification of chondrocytes in uncalcified and calcified tibial cartilage areas revealed a reduction in the number of larger hypertrophic-like cells in ABL treated mice, suggesting deceleration of hypertrophic differentiation. DISCUSSION/SIGNIFICANCE: Cartilage preservation/regeneration therapies would fill a critical unmet need. We demonstrate that an osteoporosis drug targeting PTH1R decelerates PTOA in mice. ABL treatment was associated with preservation of cartilage, decreased Col10, increased Prg4, and decreased number of large hypertrophic-like chondrocytes in the tibial cartilage.
Ralph Ellison's reputation as a major American writer has been secured in the past twenty-five years. This period has witnessed a remarkable resurgence in Ellison scholarship, stimulated partly by the availability of previously unpublished materials and the opening of The Ralph Ellison Papers in the Library of Congress. This chapter surveys major events and trends in Ellison studies since his death in 1994.
A broad survey and analysis of Wright's critical reputation from its low point at the time of his death to the great revival of interest in his work from the mid-1960s to the present day. Wright is seen not only as a major American writer but also as a transnational figure of global importance. Wright scholarship is discussed in terms of a rich historical and cultural context rooted in a number of American social and political forces as well as significant worldwide freedom movements. Careful attention is paid to major biographical studies, feminist responses to Wright's work, and new directions in Wright scholarship.
This paper explores the interaction of informal constraints on human behaviour by examining the evolution of English football jerseys. The jersey provides an excellent setting to demonstrate how informal constraints emerge from formal rules and shape human behaviour. Customs, approved norms and habits are all observed in this setting. The commercialisation of football in recent decades has resulted in these informal constraints, in many cases dating back over a century, co-existing with branding, goodwill and identity effects. Combined, these motivate clubs to maintain the status quo. As a result, club colours have remained remarkably resilient within a frequently changing landscape.
Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI.
Retrospective cohort study.
Single tertiary-care hospital.
Adult patients diagnosed with hospital-onset, healthcare facility–associated CDI from June 2014 to September 2015.
We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality.
Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe–complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23–40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72–0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90–1.09) or recurrence (OR, 0.88; 95% CI, 0.77–1.00).
Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.
Physical health outcomes in severe mental illness are worse than in the general population. Routine physical health check completion in this group is poor.
To quantitatively and qualitatively evaluate the impact of point of care (POC) blood testing on physical health check completion in community mental health services.
In a prospective cohort design, we equipped an early intervention service (EIS) and a community mental health team (CMHT) with a POC blood testing device for 6 months. We compared rates of blood test and full physical health check completion in the intervention teams with a matched EIS and CMHT, historically and during the intervention. We explored attitudes to POC testing using thematic analysis of semi-structured interviews with patients and clinicians.
Although the CMHT scarcely used the POC device and saw no change in outcomes, direct comparison of testing rates in the intervention period showed increased physical health check completion in the EIS with the device (rate ratio RR = 5.18; 95% CI 2.54–12.44; P < 0.001) compared with usual care. The rate was consistent with the EIS's increasing rate of testing over time (RR = 0.45; 95% 0.09–2.08; P = 0.32). Similar trends were seen in blood test completion. POC testing was acceptable to patients but clinicians reported usability, provision and impact on the therapeutic relationship as barriers to uptake.
POC testing was beneficial and acceptable to patients and may increase physical health check uptake. Further research, accounting for clinician barriers, is needed to evaluate its clinical and cost-effectiveness.
Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom.
A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements.
The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test.
Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.
The Iberia–Newfoundland continental margin is one of the most-studied conjugate margins in the world. However, many unknowns remain regarding the nature of rifting preceding its break-up. We analyse a large dataset of tectonic subsidence curves, created from publicly available well data, to show spatial and temporal trends of rifting in the proximal domains of the margin. We develop a novel methodology of bulk averaging tectonic subsidence curves that can be applied on any conjugate margin with a similar spread of well data. The method does not rely on the existence of conjugate, deep seismic profiles and, specifically, attempts to forego the risk of quantitative bias derived from localized anomalies and uncertain stratigraphic dating and correlation. Results for the Iberia–Newfoundland margin show that active rift-driven tectonic subsidence occurred in the Central segment of the conjugate margin from c. 227 Ma (early Norian) to c. 152.1 Ma (early Tithonian), in the southern segment from c. 208.5 Ma (early Rhaetian) to c. 152.1 Ma (early Tithonian) and in the northern segment from c. 201.3 Ma (early Hettangian) to c. 132.9 Ma (early Hauterivian). This indicates that rifting in the stretching phase of the proximal domain of the Iberia–Newfoundland margin does not mirror hyperextended domain rifting trends (south to north) that ultimately led to break-up. The insights into broad-scale three-dimensional spatial and temporal trends, produced using the novel methodology presented in this paper, provide added value for interpretation of the development of passive margins, and new constraints for modelling of the formation of conjugate margins.
The DESGW program is a collaboration between members of the Dark Energy Survey, the wider astronomical community, and the LIGO-Virgo Collaboration to search for optical counterparts of gravitational wave events, such as those expected from binary neutron star mergers or neutron star-black hole mergers. While binary black hole (BBH) events are not expected to produce an electromagnetic (EM) signature, emission is certainly not impossible. The DESGW program has performed follow-up observations of four BBH events detected by LIGO in order to search for any possible EM counterpart. Failure to find such counterparts is still relevant in that it produces limits on optical emission from such events. This is a review of follow-up results from O1 BBH events and a discussion of the status of ongoing uniform re-analysis of all BBH events that DESGW has followed up to date.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
The objective of this paper is to recall the forgotten opposition of Clément Juglar to the colonization of Algeria, the originality of this position, and his contributions to the genesis of analysing colonial institutions. Juglar was not a theoretician of colonialism, but a liberal economist who rejected the process of colonization on economic grounds. This paper provides evidence that conventional wisdom on French colonialism is indebted to his work. The issues of capital returns in the colonies, French colonialism as mercantilism and protectionism, and the role of colonial institutions in economic development were all addressed by Juglar. He identified property rights and colonial institutions as central issues in his explanation of the predictable failure of colonialism, and in doing so he can be regarded as a forerunner of neo-institutionalist analysis of colonialism.
Exclusive breast-feeding (EBF) provides optimal nutrition for infants and mothers. The practice of EBF while adhering to antiretroviral medication decreases the risk of mother-to-child transmission of HIV from approximately 25 % to less than 5 %. Thus the WHO recommends EBF for the first 6 months among HIV-infected women living in resource-limited settings; however, EBF rates remain low. In the present study our aim was to design and implement a pilot intervention promoting EBF among HIV-infected women.
The Information–Motivation–Behavioural Skills (IMB) model was applied in a brief motivational interviewing counselling session that was tested in a small randomized controlled trial.
Pietermaritzburg, South Africa, at two comparable rural public health service clinics.
Sixty-eight HIV-infected women in their third trimester were enrolled and completed baseline interviews between June and August 2014. Those randomized to the intervention arm received the IMB-based pilot intervention directly following baseline interviews. Follow-up interviews occurred at 6 weeks postpartum.
While not significantly different between trial arms, high rates of intention and practice of EBF at 6-week follow-up were reported. Findings showed high levels of self-efficacy being significantly predictive of breast-feeding initiation and duration regardless of intervention arm.
Future research must account for breast-feeding self-efficacy on sustaining breast-feeding behaviour and leverage strategies to enhance self-efficacy in supportive interventions. Supporting breast-feeding behaviour through programmes that include both individual-level and multi-systems components targeting the role of health-care providers, family and community may create environments that value and support EBF behaviour.
Various medications and devices are available for facilitation of emergent endotracheal intubations (EETIs). The objective of this study was to survey which medications and devices are being utilized for intubation by Canadian physicians.
A clinical scenario-based survey was developed to determine which medications physicians would administer to facilitate EETI, their first choice of intubation device, and backup strategy should their first choice fail. The survey was distributed to Canadian emergency medicine (EM) and intensive care unit (ICU) physicians using web-based and postal methods. Physicians were asked questions based on three scenarios (trauma; pneumonia; heart failure) and responded using a 5-point scale ranging from “always” to “never” to capture usual practice.
The survey response rate was 50.2% (882/1,758). Most physicians indicated a Macintosh blade with direct laryngoscopy would “always/often” be their first choice of intubation device in the three scenarios (mean 85% [79%-89%]) followed by video laryngoscopy (mean 37% [30%-49%]). The most common backup device chosen was an extraglottic device (mean 59% [56%-60%]). The medications most physicians would “always/often” administer were fentanyl (mean 45% [42%-51%]) and etomidate (mean 38% [25%-50%]). EM physicians were more likely than ICU physicians to paralyze patients for EETI (adjusted odds ratio 3.40; 95% CI 2.90-4.00).
Most EM and ICU physicians utilize direct laryngoscopy with a Macintosh blade as a primary device for EETI and an extraglottic device as a backup strategy. This survey highlights variation in Canadian practice patterns for some aspects of intubation in critically ill patients.
To determine the effect of graft choice (allograft, bone-patellar tendon-bone autograft, or hamstring autograft) on deep tissue infections following anterior cruciate ligament (ACL) reconstructions.
Retrospective cohort study.
SETTING AND POPULATION
Patients from 6 US health plans who underwent ACL reconstruction from January 1, 2000, through December 31, 2008.
We identified ACL reconstructions and potential postoperative infections using claims data. A hierarchical stratified sampling strategy was used to identify patients for medical record review to confirm ACL reconstructions and to determine allograft vs autograft tissue implanted, clinical characteristics, and infection status. We estimated infection rates overall and by graft type. We used logistic regression to assess the association between infections and patients’ demographic characteristics, comorbidities, and choice of graft.
On review of 1,452 medical records, we found 55 deep wound infections. With correction for sampling weights, infection rates varied by graft type: 0.5% (95% CI, 0.3%-0.8%) with allografts, 0.6% (0.1%–1.5%) with bone-patellar tendon-bone autografts, and 2.5% (1.9%–3.1%) with hamstring autograft. After adjusting for potential confounders, we found an increased infection risk with hamstring autografts compared with allografts (odds ratio, 5.9; 95% CI, 2.8–12.8). However, there was no difference in infection risk among bone-patellar tendon-bone autografts vs allografts (odds ratio, 1.2; 95% CI, 0.3–4.8).
The overall risk for deep wound infections following ACL reconstruction is low but it does vary by graft type. Infection risk was highest in hamstring autograft recipients compared with allograft recipients and bone-patellar tendon-bone autograft recipients.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
A small proportion of pediatric sport- and recreation-related injuries are serious enough to be considered “major trauma.” However, the immediate and long-term consequences in cases of pediatric major trauma are significant and potentially life-threatening. The objective of this study was to describe the incidence and outcomes of pediatric major traumas related to sport and recreational activities in Nova Scotia.
This study was a retrospective case series. Data on major pediatric traumas related to sport and recreational activities on a provincial scope were extracted from the Nova Scotia Trauma Program Registry between 2000 and 2013. We evaluated frequency, type, severity, and outcomes of major traumas. Outcomes assessed included length of hospital stay, admission to a special care unit (SCU), and mortality.
Overall, 107 children aged three to 18 years sustained a major trauma (mean age 12.5 [SD 3.8]; 84% male). Most injuries were blunt traumas (97%). The greatest proportion were from cycling (59, 53%), followed by hockey (8, 7%), skateboarding (7, 7%) and skiing (7, 7%). The Nova Scotia Pediatric Trauma Team was activated in 27% of cases. Mean in-hospital length of stay was five days (SD 5.6), and nearly half (49%) of patients required SCU admission. Severe traumatic brain injury occurred in 52% of cases, and mortality in five cases.
Over a 13-year period, the highest incidence of pediatric major trauma related to sport and recreational activities was from cycling, followed by hockey. Severe traumatic brain injury occurred in over half of pediatric major trauma patients.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.