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No evidence-based therapy for borderline personality disorder (BPD) exhibits a clear superiority. However, BPD is highly heterogeneous, and different patients may specifically benefit from the interventions of a particular treatment.
From a randomized trial comparing a year of dialectical behavior therapy (DBT) to general psychiatric management (GPM) for BPD, long-term (2-year-post) outcome data and patient baseline variables (n = 156) were used to examine individual and combined patient-level moderators of differential treatment response. A two-step bootstrapped and partially cross-validated moderator identification process was employed for 20 baseline variables. For identified moderators, 10-fold bootstrapped cross-validated models estimated response to each therapy, and long-term outcomes were compared for patients randomized to their model-predicted optimal v. non-optimal treatment.
Significant moderators surviving the two-step process included psychiatric symptom severity, BPD impulsivity symptoms (both GPM > DBT), dependent personality traits, childhood emotional abuse, and social adjustment (all DBT > GPM). Patients randomized to their model-predicted optimal treatment had significantly better long-term outcomes (d = 0.36, p = 0.028), especially if the model had a relatively stronger (top 60%) prediction for that patient (d = 0.61, p = 0.004). Among patients with a stronger prediction, this advantage held even when applying a conservative statistical check (d = 0.46, p = 0.043).
Patient characteristics influence the degree to which they respond to two treatments for BPD. Combining information from multiple moderators may help inform providers and patients as to which treatment is the most likely to lead to long-term symptom relief. Further research on personalized medicine in BPD is needed.
During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.
Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses.
The Cavan–Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life.
Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct.
There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.
To update current estimates of non–device-associated pneumonia (ND pneumonia) rates and their frequency relative to ventilator associated pneumonia (VAP), and identify risk factors for ND pneumonia.
Academic teaching hospital.
All adult hospitalizations between 2013 and 2017 were included. Pneumonia (device associated and non–device associated) were captured through comprehensive, hospital-wide active surveillance using CDC definitions and methodology.
From 2013 to 2017, there were 163,386 hospitalizations (97,485 unique patients) and 771 pneumonia cases (520 ND pneumonia and 191 VAP). The rate of ND pneumonia remained stable, with 4.15 and 4.54 ND pneumonia cases per 10,000 hospitalization days in 2013 and 2017 respectively (P = .65). In 2017, 74% of pneumonia cases were ND pneumonia. Male sex and increasing age we both associated with increased risk of ND pneumonia. Additionally, patients with chronic bronchitis or emphysema (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.40–3.06), congestive heart failure (HR, 1.48; 95% CI, 1.07–2.05), or paralysis (HR, 1.72; 95% CI, 1.09–2.73) were also at increased risk, as were those who were immunosuppressed (HR, 1.54; 95% CI, 1.18–2.00) or in the ICU (HR, 1.49; 95% CI, 1.06–2.09). We did not detect a change in ND pneumonia risk with use of chlorhexidine mouthwash, total parenteral nutrition, all medications of interest, and prior ventilation.
The incidence rate of ND pneumonia did not change from 2013 to 2017, and 3 of 4 nosocomial pneumonia cases were non–device associated. Hospital infection prevention programs should consider expanding the scope of surveillance to include non-ventilated patients. Future research should continue to look for modifiable risk factors and should assess potential prevention strategies.
To update current estimates of non–device-associated urinary tract infection (ND-UTI) rates and their frequency relative to catheter-associated UTIs (CA-UTIs) and to identify risk factors for ND-UTIs.
Academic teaching hospital.
All adult hospitalizations between 2013 and 2017 were included. UTIs (device and non-device associated) were captured through comprehensive, hospital-wide active surveillance using Centers for Disease Control and Prevention case definitions and methodology.
From 2013 to 2017 there were 163,386 hospitalizations (97,485 unique patients) and 1,273 UTIs (715 ND-UTIs and 558 CA-UTIs). The rate of ND-UTIs remained stable, decreasing slightly from 6.14 to 5.57 ND-UTIs per 10,000 hospitalization days during the study period (P = .15). However, the proportion of UTIs that were non–device related increased from 52% to 72% (P < .0001). Female sex (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.50–2.50) and increasing age were associated with increased ND-UTI risk. Additionally, the following conditions were associated with increased risk: peptic ulcer disease (HR, 2.25; 95% CI, 1.04–4.86), immunosuppression (HR, 1.48; 95% CI, 1.15–1.91), trauma admissions (HR, 1.36; 95% CI, 1.02–1.81), total parenteral nutrition (HR, 1.99; 95% CI, 1.35–2.94) and opioid use (HR, 1.62; 95% CI, 1.10–2.32). Urinary retention (HR, 1.41; 95% CI, 0.96–2.07), suprapubic catheterization (HR, 2.28; 95% CI, 0.88–5.91), and nephrostomy tubes (HR, 2.02; 95% CI, 0.83–4.93) may also increase risk, but estimates were imprecise.
Greater than 70% of UTIs are now non–device associated. Current targeted surveillance practices should be reconsidered in light of this changing landscape. We identified several modifiable risk factors for ND-UTIs, and future research should explore the impact of prevention strategies that target these factors.
Paragonimiasis, human lung fluke disease, is a foodborne anthropozoonosis caused by the trematodes assigned to Paragonimus and is regarded by the World Health Organization as a Neglected Tropical Disease (NTD). The life cycle of this medically important parasite centres on a complex freshwater biological community that includes two intermediate hosts: a mollusc and a decapod, usually a brachyuran. Although there is a perception that the biology, symptoms, diagnosis and treatment of Paragonimus is well understood, in reality, this is not the case, especially in Africa. Much remains unknown concerning the life-cycle of the parasite, its transmission, the current epidemiology of the disease, diagnosis and the effectiveness of treatment. Furthermore, cases of paragonimiasis may be misdiagnosed as resistant tuberculosis (TB) because of the similar pulmonary symptoms and no remission after anti TB therapy. The endemic foci of human paragonimiasis in Africa have been reported mainly in the forest zones of Upper Guinea (Liberia, Guinea and Ivory Coast) and Lower Guinea (Nigeria, Cameroon, Equatorial Guinea and Gabon). Despite the perceived medical importance of paragonimiasis, relatively little attention has been paid to this NTD since its discovery in Africa in the 1960s. This review focuses on the current understanding of the life cycle and transmission of Paragonimus in Africa, discusses its diagnosis and public health importance and highlights many outstanding gaps in the knowledge that still exist for this NTD.
The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Rapid, non-destructive methods for measuring seed germination and vigour are valuable. Standard germination and seed vigour were determined using 81 soybean seed lots. From these data, seed lots were separated into high and low germinating seed lots as well as high, medium and low vigour seed lots. Near-infrared spectra (950–1650 nm) were collected for training and validation samples for each seed category and used to create partial least squares (PLS) prediction models. For both germination and vigour, qualitative models provided better discrimination of high and low performing seed lots compared with quantitative models. The qualitative germination prediction models correctly identified low and high germination seed lots with an accuracy between 85.7 and 89.7%. For seed vigour, qualitative predictions for the 3-category (low, medium and high vigour) models could not adequately separate high and medium vigour seeds. However, the 2-category (low, medium plus high vigour) prediction models could correctly identify low vigour seed lots between 80 and 100% and the medium plus high vigour seed lots between 96.3 and 96.6%. To our knowledge, the current study is the first to provide near-infrared spectroscopy (NIRS)-based predictive models using agronomically meaningful cut-offs for standard germination and vigour on a commercial scale using over 80 seed lots.
Although hospital emergency preparedness efforts have been recognized as important, there has been growing pressure on cost containment, as well as consolidation within the US health care system. There is little data looking at what health care emergency preparedness functions have been, could be, or should be centrally coordinated at a system level.
We developed a questionnaire for academic health systems and asked about program funding, resources provided, governance, and activities. The questionnaire also queried managers’ opinions regarding the appropriate role for the system-level resources in emergency response, as well as about what is most helpful at the system-level supporting preparedness.
Fifty-two of 97 systems (54%) responded. The most frequently occurring system-wide activities included: creating trainings or exercise templates (75%), promoting preparedness for employees in the system (75%), providing access to specific subject matter experts (73%), and developing specific plans for individual member entities within their system (73%). The top resources provided included a common mass notification system (71%), arranging for centralized contracts for goods and services (71%), and providing subject matter expertise (69%).
Currently, there is wide variation in the resources, capabilities, and programs used to support and coordinate system-level emergency preparedness among academic health systems. (Disaster Med Public Health Preparedness. 2018;12:574–577)
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.
Introduction: Many barriers exist to integrating smoking cessation into delivery of lung cancer screening including limited provider time and patient misconceptions.
Aims: To demonstrate that proactive outreach from a telephone counsellor outside of the patient's usual care team is feasible and acceptable to patients.
Methods: Smokers undergoing lung cancer screening were approached for a telephone counselling study. Patients agreeing to participate in the intervention (n = 27) received two telephone counselling sessions. A 30-day follow-up evaluation was conducted, which also included screening participants receiving usual care (n = 56).
Results/Findings: Most (89%) intervention participants reported being satisfied with the proactive calls, and 81% reported the sessions were helpful. Use of behavioural cessation support programs in the intervention group was four times higher (44%) compared to the usual care group (11%); Relative Risk (RR) = 4.1; 95% CI: 1.7 to 9.9), and seven-day abstinence in the intervention group was double (19%) compared to the usual care group (7%); RR = 2.6; 95% CI: 0.8 to 8.9).
Conclusions: This practical telephone-based approach, which included risk messages clarifying continued risks of smoking in the context of screening results, suggests such messaging can boost utilisation of evidence-based tobacco treatment, self-efficacy, and potentially increase the likelihood of successful quitting.
OBJECTIVES/SPECIFIC AIMS: Obesity is a rapidly growing epidemic and long-term interventions aimed to reduce body weight are largely unsuccessful due to an increased drive to eat and a reduced metabolic rate established during weight loss. Previously, our lab demonstrated that exercise has beneficial effects on weight loss maintenance by increasing total energy expenditure above and beyond the cost of an exercise bout and reducing the drive to eat when allowed to eat ad libitum (relapse). We hypothesized that exercise’s ability to counter these obesogenic-impetuses are mediated via improvements in skeletal muscle oxidative capacity, and tested this using a mouse model with augmented oxidative capacity in skeletal muscle. METHODS/STUDY POPULATION: We recapitulated the exercise-induced improvements in oxidative capacity using FVB mice that overexpress lipoprotein lipase in skeletal muscle (mLPL). mLPL and wild type (WT) mice were put through a weight-loss-weight-regain paradigm consisting of a high fat diet challenge for 13 weeks, with a subsequent 1-week calorie-restricted medium fat diet to induce a ~15% weight loss. This newly established weight was maintained for 2 weeks and followed with a 24-hour relapse. Metabolic phenotype was characterized by indirect calorimetry during each phase. At the conclusion of the relapse day, mice were sacrificed and tissues were harvested for molecular analysis. RESULTS/ANTICIPATED RESULTS: During weight loss maintenance, mLPL mice had a higher metabolic rate (p=0.0256) that was predominantly evident in the dark cycle (p=0.0015). Furthermore, this increased metabolic rate was not due to differences in activity (p=0.2877) or resting metabolic rate (p=0.4881). During relapse, mLPL mice ingested less calories and were protected from rapid weight regain (p=0.0235), despite WT mice exhibiting higher metabolic rates during the light cycle (p=0.0421). DISCUSSION/SIGNIFICANCE OF IMPACT: These results highlight the importance of muscular oxidative capacity in preventing a depression in total energy expenditure during weight loss maintenance, and in curbing overfeeding and weight regain during a relapse. Moreover, our data suggest that the thermic effect of food is responsible for the differences in metabolic rate, because no differences were found in activity or resting metabolic rate. Additional studies are warranted to determine the molecular mechanisms driving the ability of oxidative capacity to assist with weight loss maintenance.
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36–54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.
Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ– or Aβ+.
At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ– Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.
While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.
We present low-frequency spectral energy distributions of 60 known radio pulsars observed with the Murchison Widefield Array telescope. We searched the GaLactic and Extragalactic All-sky Murchison Widefield Array survey images for 200-MHz continuum radio emission at the position of all pulsars in the Australia Telescope National Facility (ATNF) pulsar catalogue. For the 60 confirmed detections, we have measured flux densities in 20 × 8 MHz bands between 72 and 231 MHz. We compare our results to existing measurements and show that the Murchison Widefield Array flux densities are in good agreement.