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Purpose: Early evidence supports the safety and efficiency of extended scope speech-language pathology (SLP) clinics designed to manage low risk ear nose and throat (ENT) outpatient referrals, howe...

Objectives: Tourette syndrome (TS) is characterized by the presence of sudden, rapid movements and vocalizations (tics). The nature of tics suggests impairments in inhibitory control. However, findings of impaired inhibitory control have so far been inconsistent, possibly due to small sample sizes, wide age ranges, or not taking medication use or attention-deficit/hyperactivity disorder (ADHD) comorbidity into account. Methods: We investigated group differences in response inhibition using an fMRI-based stop-signal task in 103 8-12-year-old children (n = 51 with TS, of whom n = 28 without comorbid ADHD [TS–ADHD] and n = 23 with comorbid ADHD [TS + ADHD]; and n = 52 healthy controls), and related these measures to tic and ADHD severity. Results: We observed an impaired response inhibition performance in children with TS + ADHD, but not in those with TS–ADHD, relative to healthy controls, as evidenced by a slower stop-signal reaction time, slower mean reaction times, and larger variability of reaction times. Dimensional analyses implicated ADHD severity as the driving force in these findings. Neural activation during failed inhibition was stronger in the inferior frontal gyrus and temporal and parietal areas in TS + ADHD compared to healthy controls. Conclusions: Impaired inhibitory performance and increased neural activity in TS appear to manifest predominantly in relation to ADHD symptomatology.

Aim Children with middle ear disease often experience lengthy delays waiting for outpatient paediatric ear nose and throat (ENT) services. This study aimed to investigate whether an alternative service delivery model using audiologists working in an expanded scope of practice reduced waiting times for children to access such services. Methods A total of 131 children consecutively referred to a large ENT outpatient service in Queensland, Australia, for middle ear and hearing concerns were prospectively allocated to either a standard ENT service or an advanced audiology (AA)-led service. Waiting times and attendance rates were collected and compared between the two patient groups. Results The median waiting time from referral to first offered appointment was 96 days for children in the AA-led service versus 417.5 days for children in the standard ENT service. Seventy-nine percent of children in the AA-led service attended their first offered appointment versus 61% in the standard ENT service. For children receiving grommets, the median waiting time from initial referral to grommet insertion was 226 days for children in the AA-led service versus 627 days for children in the standard ENT service. Conclusion The AA-led service was an effective alternative pathway to reduce waiting times for children referred to ENT services with middle ear and hearing concerns.

Setting This paper documents a participatory process of Health Portfolio staff in the design of a clock, and announces the 2020 Canadian Health Clock, with links to numerous online health calculators. The clock is part of the Health Portfolio’s celebration activities in 2019 of “100 Years of Health”, as the Department of Health was established in Canada in 1919. Intervention The intervention was the development of a clock on the Government of Canada website with linkage to calculators as a health promotion tool. The clock was built on the concept of the 2004 Chronic Disease Clock, which shows the number of deaths so far today, and so far this year. The clock was developed using a consultative approach, following a review of the original clock. Outcomes The 2020 clock incorporates new data visualization concepts. New features, facilitated by improved technology, include: expansion to all causes of death; blinking red dots to enhance visual impact; and three clock versions (analogue, featuring a moving circle; digital, table format; and graphical, bar chart format). The clock also provides links to a number of health calculators, to allow people to seek personalized information to improve their health. Implications The online health clock and health calculators are good examples of innovation in health risk communication tools for effective knowledge translation and dissemination. They inform people about health statistics (clock) and their health (calculators). The clock engages people in the context of the Canadian population, whereas the calculators provide personalized information about improving an individual’s future health.

Introduction: Sickle Cell Disease (SCD) is an inherited haemolytic disorder that affects virtually all body systems including the eye. Ocular complications of SCD could have dire consequences if not detected early. Objectives: We aimed at determining the prevalence of ocular complications of SCD in our patients. Methods: This study was carried out on patients attending both the adult and Paediatric Sickle cell disease clinic at Chukwuemeka Odumegwu Ojukwu Teaching Hospital, Akwa, Anambra State, Nigeria, over an 8 month period. A structured questionnaire was administered to consenting patients to determine their sociodemographic variables and other characteristics. Visual acuity was determined with multiple optotype Snellen’s chart at 6 metres in natural daylight. Using pen-torch, the face, external eye examination, anterior segment examination and pupillary reaction to light were assessed. Magnified anterior segment examination was performed with slit-lamp biomicroscope. All subjects underwent dilated fundoscopy (after instillation of tropicamide 0.5% eye drop) using Welch Allyn indirect ophthalmoscope. Results were analysed using SPSS version 22.0 Inc Chicago Illinois and represented in tables. Statistically significant P value was set at < 0.05. Results: A total of 28 patients with age range of 6-42 years were seen. 17 (60.7%) were males, while 11 (39.3%) were females. 8 (28.6%) had at least one ocular anomaly comprising of refractory errors 3 (10.8%), sickle cell retinopathy 4 (14.3%) and glaucoma 2 (7.1%). Only 2 (7.1%) routinely visit eye clinic. SCD retinopathy was found to increase with age (P value= 0.005). Conclusion: SCD retinopathy was found more in the older age group despite the small sample size at a prevalence rate of 14.3%. Early initiation of routine ocular examination for SCD patients will be beneficial to avert these complications. More efforts should be made at educating the patients. Larger studies will be required to determine the actual prevalence of ocular anomaly in SCD patients in Anambra State.

OBJECTIVES: Expansion of the scopes of practice of allied health practitioners has the potential to improve the efficiency and cost-effectiveness of healthcare, given the identified shortages in medical personnel. Despite numerous examples in other allied health disciplines, this has yet to be applied to pediatric Audiology. This study aimed to investigate the effectiveness and safety of using audiologists with advanced training to independently triage children referred to otolaryngology (ORL) services, and compare the subsequent use of specialist resources, and postoperative grommet care to a standard medical ORL service. DESIGN: One hundred twenty children consecutively referred to a large ORL outpatient service in Queensland, Australia, for middle ear and hearing concerns were prospectively allocated to either the ORL service or Advanced Audiology-led service. Demographic and clinical data were extracted from electronic medical records and compared between the two services. Clinical incidents and adverse events were recorded for the Advanced Audiology-led service. RESULTS: Approximately half of all children referred to ORL for middle ear or hearing concerns were discharged without requiring any treatment, with the remaining half offered surgical treatment. The Advanced Audiology-led model increased the proportion of children assessed by ORL that proceeded to surgery from 57% to 82% compared with the standard medical ORL model. Children followed up by the audiologists after grommet insertion were more likely to be discharged independently and at the first postoperative review appointment compared with the standard medical ORL service. There were no reports of adverse events or long-term bilateral hearing loss after discharge by the Advanced Audiology-led service. CONCLUSIONS: These findings indicate that an Advanced Audiology-led service provides a safe and effective triaging model for the independent management of children not requiring treatment, and children requiring routine postoperative grommet review, and improves the effective use of specialist resource compared with the standard medical ORL service.

The advanced audiology-led service is designed to triage and manage children who are referred to Ear Nose and Throat (ENT) outpatient services with middle ear or hearing concerns. This service has resulted in shorter waiting times for children to receive ENT treatment, and improved ENT capacity. The aim of this study was to explore parental satisfaction with the advanced audiology-led ENT service and to determine if there were cultural or process factors affecting satisfaction.Prospective cross-sectional study using a modified Visit-Specific Satisfaction Questionnaire (VSQ-9) survey.One hundred and thirteen parents of children consecutively attending a first appointment in the advanced audiology-led service recruited between October 2016 and October 2017.There were a total of 100 valid responses (rate of 88.5%). The survey showed high levels of satisfaction. Satisfaction scores were significantly higher for items related to interactions with the audiologist compared to items related to waiting times. There were no differences in satisfaction across cultural groups. Parents were equally satisfied with the service whether their child was managed independently by the audiologist or required another appointment for medical input.The advanced audiology-led service had high levels of satisfaction from parents attending with their children.

Although much research has been devoted to the neural correlates of motion perception, the processing of speed of motion is still a topic of discussion. Apart from patient LM, no in-depth clinical research has been done in the past 20 years on this topic. In the present study, we investigated patient TD, who suffered from the rare disorder akinetopsia due to bilateral lesions of V5 after stroke. By means of a Random-Dot-Kinematogram (RDK) in which speed was varied systematically, it was found that TD was impaired in perceiving the direction of movement at speeds exceeding 9 deg/s. Our study suggests that V5 plays an important role in processing high-speed visual motion and further implies that V5 does not play a crucial role in processing low-speed visual motion. A remarkable finding, which has not been shown before, was that TD always reported the opposite direction of the actual movement at a speed of 24 deg/s. This suggests a form of the continuous wagon wheel illusion, which might have been caused by intact brain areas operating at different sampling rates than area V5.

The aim of this study was to investigate whether apathy in schizophrenia is associated with rigidity in behavior and brain functioning. To this end, we studied associations between variability in dynamic functional connectivity (DFC) in relevant functional brain networks, apathy, and variability in physical activity in schizophrenia. Thirty-one patients with schizophrenia, scoring high on apathy, were included and wore an actigraph. Activity variability was calculated on the activity counts using the root of the Mean Squared Successive Difference (MSSD). Furthermore, we calculated DFC on resting-state data as phase interactions between blood oxygen-level dependent (BOLD) signals of 270 brain regions per volume. Variability (MSSD) in DFC was calculated for 3 networks, including the default-mode network (DMN), frontoparietal network, and salience-reward network (SRN). Finally, we calculated correlations between these DFC estimates and apathy and activity variability. First, lower activity variability was associated with higher levels of apathy. Second, higher levels of apathy were associated with lower variability in DFC in the DMN and SRN. Third, higher activity variability was associated with higher variability in DFC in the SRN. In conclusion, patients with schizophrenia and more severe levels of apathy showed less variability in their physical activity and more rigid functional brain network behavior in the DMN and SRN. These networks have been shown relevant for self-reflection, mental simulation, and reward processing, processes that are pivotal for self-initiated goal-directed behavior. Functional rigidity of these networks may therefore contribute to reduced goal-directed behavior, which is characteristic for these patients.

Purpose: To solve complex health issues, an innovative and multidisciplinary framework is necessary. The Clinical Public Health (CPH) Division was established at the University of Toronto (UofT), Canada to foster inte-gration of primary care, preventive medicine and public health in education, practice and research. To better understand how the construct of CPH might be applied, we surveyed clinicians, researchers and public health professionals affiliated with the CPH Division to assess their understanding of the CPH concept and its utility in fostering broad collaboration. Methods: A two-wave anonymous survey of the active faculty of the CPH Division, UofT was conducted across Canada. Wave 1 participants (n = 187; 2016) were asked to define CPH, while Wave 2 participants (n = 192; 2017) were provided a synthesis of Wave 1 results and asked to rank each definition. Both waves were asked about the need for a common definition, and to comment on CPH. Results: Response rates for the first and second waves were 25% and 22%, respectively. Of the six definitions of CPH from Wave 1, “the intersection of clinical practice and public health,” was most highly ranked by Wave 2 participants. Positive perceptions of CPH included multidisciplinary collaboration, new fields and insights, forward thinking and innovation. Negative perceptions included CPH being a confusing term, too narrow in scope or too clinical. Conclusion: The concept of Clinical Public Health can foster multidisciplinary collaboration to address com-plex health issues because it provides a useful framework for bringing together key disciplines and diverse professional specialties.

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Highlights • Post-mTBI fatigue relates to visual processing and effort perception. • Fatigue correlates with activity in the extrastriate cortex and left midcingulate. • CNS drive during a sustained effort correlates with post-contraction BOLD-activity. • Insular and midcingulate activation suggests changes in cortical homeostasis., Introduction Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. Methods Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. Results The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p

Highlights • In aMCI, apathy severity was associated with lower FA in widespread WM pathways. • WM aberrations are related to apathy severity after controlling for depression. • Disruptions related to apathy severity are not limited to frontal-subcortical area., Apathy is recognized as a prevalent behavioral symptom of amnestic Mild Cognitive Impairment (aMCI). In aMCI, apathy is associated with an increased risk and increases the risk of progression to Alzheimer’s Disease (AD). Previous DTI study in aMCI showed that apathy has been associated with white matter alterations in the cingulum, middle and inferior longitudinal fasciculus, fornix, and uncinate fasciculus. However, the underlying white matter correlates associated with apathy in aMCI are still unclear. We investigated this relationship using whole-brain diffusion tensor imaging (DTI). Twenty-nine aMCI patients and 20 matched cognitively healthy controls were included. Apathy severity was assessed using the Apathy Evaluation Scale Clinician version. We applied the tract-based spatial statistics analyses to DTI parameters: fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity to investigate changes in white matter pathways associated with the severity of apathy. No significant difference was found in any of the DTI parameters between aMCI and the control group. In aMCI, higher severity of apathy was associated with lower FA in various white matter pathways including the left anterior part of inferior fronto-occipital fasciculus/uncinate fasciculus, genu and body of the corpus callosum, superior and anterior corona radiata, anterior thalamic radiation of both hemispheres and in the right superior longitudinal fasciculus/anterior segment of arcuate fasciculus (p

Background This study aimed to reduce the total waiting time for high-end health screening processes. Method The subjects of this study were recruited from a health screening center in a tertiary hospital in northern Taiwan from September 2016 to February 2017, where a total of 2342 high-end customers participated. Three policies were adopted for the simulation. Results The first policy presented a predetermined proportion of customer types, in which the total waiting time was increased from 72.29 to 83.04 mins. The second policy was based on increased bottleneck resources, which provided significant improvement, decreasing the total waiting time from 72.29 to 28.39 mins. However, this policy also dramatically increased the cost while lowering the utilization of this health screening center. The third policy was adjusting customer arrival times, which significantly reduced the waiting time—with the total waiting time reduced from 72.29 to 55.02 mins. Although the waiting time of this policy was slightly longer than that of the second policy, the additional cost was much lower. Conclusions Scheduled arrival intervals could help reduce customer waiting time in the health screening department based on the “first in, first out” rule. The simulation model of this study could be utilized, and the parameters could be modified to comply with different health screening centers to improve processes and service quality.

The ability to maintain postural stability is essential in our daily lives. Relatedly, hemiparetic stroke patients have a very high risk of falls. This study aimed to improve the traditional rehabilitation treatment for stroke patients with hemiparesis by providing a virtual reality (VR) feedback system with modular interactive tiles (MITs) to enhance their postural stability and thus prevent falls. The data collected included pre-test and post-test Berg Balance Scale (BBS) values, and complexity index (CI) values for center of pressure (COP) data based on multiscale entropy (MSE) and multivariate multiscale entropy (MMSE) at the 12-week exercise program. Higher BBS and CI values indicate better postural stability, and the results showed that the exercise program yielded significant improvements in postural stability. The mean pre-test BBS value of 51.67 &plusmn, 3.12 increased to 53.83 &plusmn, 2.17 (p &lt, 0.05), and the mean CI of MMSE value increased by 14.8% (p &lt, 0.01). We confirmed that this training program including MITs is beneficial to the rehabilitation of stroke patients. More specifically, the MITs training program positively affected the CI of MMSE values, and the affected result similar to the BBS values of the patients, indicating their improved balance and ability to avoid falls.

This paper describes chronic features of neuroangiostrongyliasis (NAS), a long-term outcome of the disease that has not been adequately described. Current and past literature is predominantly limited to acute manifestations of NAS, and mention of chronic, ongoing clinical symptoms is usually limited to brief notes in a discussion of severe cases. This study investigated the long-term outcomes in ten individuals who were diagnosed with acute neuroangiostrongyliasis in Hawaii between 2009 and 2017. The study demonstrates a significant number of persons in Hawaii sustain residual symptoms for many years, including troublesome sensory paresthesia (abnormal spontaneous sensations of skin experienced as ‘burning, pricking, pins and needles’; also described as allodynia or hyperesthesia) and extremity muscle pains. As a consequence, employment and economic hardships, domestic relocations, and psychological impairments affecting personal relationships occurred. The study summarizes common features of chronic disease, sensory paresthesia and hyperesthesia, diffuse muscular pain, insomnia, and accompanying emotional distress; highlights the frequently unsuccessful endeavours of individuals struggling to find effective treatment; proposes pathogenic mechanisms responsible for prolonged illness including possible reasons for differences in disease presentation in Hawaii compared to Southeast Asia.

BackgroundThe importance of the hippocampus and amygdala for disrupted emotional memory formation in depression is well-recognized, but it remains unclear whether functional abnormalities are state-dependent and whether they are affected by the persistence of depressive symptoms.MethodsThirty-nine patients with major depressive disorder and 28 healthy controls were included from the longitudinal functional magnetic resonance imaging (fMRI) sub-study of the Netherlands Study of Depression and Anxiety. Participants performed an emotional word-encoding and -recognition task during fMRI at baseline and 2-year follow-up measurement. At baseline, all patients were in a depressed state. We investigated state-dependency by relating changes in brain activation over time to changes in symptom severity. Furthermore, the effect of time spent with depressive symptoms in the 2-year interval was investigated.ResultsSymptom change was linearly associated with higher activation over time of the left anterior hippocampus extending to the amygdala during positive and negative word-encoding. Especially during positive word encoding, this effect was driven by symptomatic improvement. There was no effect of time spent with depression in the 2-year interval on change in brain activation. Results were independent of medication- and psychotherapy-use.ConclusionUsing a longitudinal within-subjects design, we showed that hippocampal–amygdalar activation during emotional memory formation is related to depressive symptom severity but not persistence (i.e. time spent with depression or ‘load’), suggesting functional activation patterns in depression are not subject to functional ‘scarring’ although this hypothesis awaits future replication.

The role of human papillomavirus type 16 (HPV16) in oral potentially malignant disorders (OPMD) and oral cavity carcinoma (OC) is still under debate. We investigated HPV16 prevalence in unstimulated saliva, oral rinse samples, oral swabs and tumour biopsies collected from OPMD (n = 83) and OC (n = 106) patients. HPV16 genotype, viral load, physical status (episomal vs. integrated) and tumour p16INK4a expression were determined. Oral HPV16 prevalence was higher in OC than in OPMD, but this difference was not statistically significant (7.5% (8/106) versus 3.6% (3/83), odds ratio (OR): 2.18, 95% confidence interval (CI): 0.56, 8.48, p = 0.26). There was a significant association (p &lt, 0.05) between oral HPV16 infection and heavy tobacco consumption. Real-time PCR results indicated that no integration events occurred in either OPMD or OC cases based on the HPV16 E2/E6 ratio. HPV16 positive OPMD and OC patients had similar HPV16 E2 and E6 viral loads. The inter-rater agreement between tumour p16INK4a expression and oral HPV16 infection was considered as fair (k = 0.361) for OC. Our data suggest that the involvement of HPV16 in oral carcinogenesis is limited.

An MR headset experience is only as good as its combined display and sensor systems. Thus, motion-to-photon (MTP) latency is a critical spec that defines the quality of the visual and global sensory experience. MTP latency is also instrumental in reducing the well-documented VR/AR motion sickness (vestibular nausea).

Background Apathy, a common neuropsychiatric (NPS) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), is associated with structural and metabolic brain changes. However, functional connectivity changes across the brain in association with apathy remain unclear. In this study, graph theoretical measures of integration and segregation from resting state functional connectivity in MCI and AD patients with low depression scores, and healthy controls. Methods In MCI and AD patients with low depression scores, graph theoretical measures of integration and segregation were derived from resting state functional connectivity in patients, which were compared between those with apathy (NPS_A, n = 21) to those without NPS (NPS_None, n = 28) and those with NPS other than apathy (NPS_NA, n = 38). Additionally, the same measures were compared between AD patients and healthy controls (amyloid uptake below threshold levels). Results Altered whole brain global efficiency and reduced local efficiency were found in NPS_A compared to NPS_None and NPS_NA. In similar contrasts, apathy was associated with increased participation coefficient in the frontoparietal and cingulo-opercular template-based networks. A study-specific network definition also showed similar results. In comparison, AD patients showed higher modularity compared to controls at the whole brain level and higher participation coefficient in the ventral attention network. Limitations The severity and dimensions of apathy were not assessed. Conclusions Loss of segregation in the frontoparietal and cingulo-opercular network, which are involved in the control of goal-directed behavior, was associated with apathy in MCI/AD. The results also suggest that network-level changes in AD patients may underlie specific NPS.

Little is known about the brain's functional organization during resting-state in children with Tourette syndrome (TS). We aimed to investigate this with a specific focus on the role of comorbid attention-deficit/hyperactivity disorder (ADHD). We applied graph theoretical analysis to resting-state functional magnetic resonance imaging data of 109 8-to-12-year-old children with TS (n = 46), ADHD without tics (n = 23), and healthy controls (n = 40). First, we compared these three groups, and in a second comparison four groups, distinguishing TS with (TS + ADHD, n = 19) and without comorbid ADHD (TS−ADHD, n = 27). Weighted brain graphs were constructed for both comparisons to investigate global efficiency, local efficiency, and clustering coefficient per acquired network. Local efficiency and clustering coefficient were significantly lower in children with TS−ADHD in the default mode network compared with healthy controls, and in the frontoparietal network compared with ADHD; we also found associations with higher tic severity. Our study supports a different functional brain network organization in children with TS−ADHD, compared with healthy controls and children with ADHD.

Background Antibiotic use is a well-known risk factor for acquisition of drug-resistant bacteria and community antibiotic prescribing can drive high rates of resistance within the hospital setting. Owing to concerns over increasing fluoroquinolone (FQ) resistance among Gram-negative organisms at UAB Hospital, our stewardship program implemented a pre-authorization policy. The goal of this study was to assess the relationship between hospital fluoroquinolone use and antibiotic resistance. Methods In 2006, the inpatient formulary was consolidated to only ciprofloxacin and moxifloxacin with implementation of guidelines for use to limit inpatient prescribing. Any use outside of these guidelines required approval from an infectious diseases physician. Organism-specific data were obtained from the clinical microbiology database and FQ use was obtained from the hospital database. Correlations were calculated using Pearson’s coefficient. Results From 1998 to 2004, FQ use peaked at 173 days of therapy (DOT)/1,000 patient-days, but has remained below 60 DOT/1,000 patient-days since restriction implementation (Figure 1). FQ susceptibility was documented for five common Gram-negative isolates, P. aeruginosa, Acinetobacter spp., Enterobacter cloacae, E. coli, and K. pneumoniae, over an 18-year period (1998–2016). Common hospital acquired pathogens, including Pseudomonas aeruginosa, Acinetobacter spp. and Enterobacter cloacae improved in their susceptibilities to fluoroquinolones. Acinetobacter went from 35% to over 50% susceptible in the preceding 10 years after the policy. Pseudomonas improved from 50% susceptible to over 70% and Enterobacter improved from less than 50% to over 90% susceptible. Interestingly this improvement was not seen for E. coli which continued to show a decline in susceptibility from over 90% to near 60% in 2016. Conclusion In a large academic hospital setting, FQ susceptibility for common hospital-acquired GNRS improved significantly with the introduction of a restricted use program. A continued decline in E. coli FQ susceptibility suggests resistance rates may be driven by outpatient and community antibiotic use and thus, outpatient stewardship programs are necessary to prevent further spread of FQ resistance. Disclosures All authors: No reported disclosures.

BackgroundMajor Depressive Disorder (MDD) is a psychiatric disorder with a highly recurrent character, making prevention of relapse an important clinical goal. Preventive Cognitive Therapy (PCT) has been proven effective in preventing relapse, though not for every patient. A better understanding of relapse vulnerability and working mechanisms of preventive treatment may inform effective personalized intervention strategies. Neurocognitive models of MDD suggest that abnormalities in prefrontal control over limbic emotion-processing areas during emotional processing and regulation are important in understanding relapse vulnerability. Whether changes in these neurocognitive abnormalities are induced by PCT and thus play an important role in mediating the risk for recurrent depression, is currently unclear.In the Neurocognitive Working Mechanisms of the Prevention of Relapse In Depression (NEWPRIDE) study, we aim to 1) study neurocognitive factors underpinning the vulnerability for relapse, 2) understand the neurocognitive working mechanisms of PCT, 3) predict longitudinal treatment effects based on pre-treatment neurocognitive characteristics, and 4) validate the pupil dilation response as a marker for prefrontal activity, reflecting emotion regulation capacity and therapy success.MethodsIn this randomized controlled trial, 75 remitted recurrent MDD (rrMDD) patients will be included. Detailed clinical and cognitive measurements, fMRI scanning and pupillometry will be performed at baseline and three-month follow-up. In the interval, 50 rrMDD patients will be randomized to eight sessions of PCT and 25 rrMDD patients to a waiting list. At baseline, 25 healthy control participants will be additionally included to objectify cross-sectional residual neurocognitive abnormalities in rrMDD. After 18 months, clinical assessments of relapse status are performed to investigate which therapy induced changes predict relapse in the 50 patients allocated to PCT.DiscussionThe present trial is the first to study the neurocognitive vulnerability factors underlying relapse and mediating relapse prevention, their value for predicting PCT success and whether pupil dilation acts as a valuable marker in this regard. Ultimately, a deeper understanding of relapse prevention could contribute to the development of better targeted preventive interventions.Trial registrationTrial registration: Netherlands Trial Register, August 18, 2015, trial numberNL5219.

Background Clostridioides difficile infections (CDIs) have been identified as a major health concern due to the high morbidity, mortality, and cost of treatment. The aim of this study was to review the extant literature and identify the various patient-related, medication-related, and organizational risk factors associated with developing hospital-acquired CDIs in adult patients in the United States. Methods A systematic review of four (4) online databases, including Scopus, PubMed, CINAHL, and Cochrane Library, was conducted to identify empirical studies published from 2007 to 2017 pertaining to risk factors of developing hospital-acquired CDIs. Findings Thirty-eight studies (38) were included in the review. Various patient-level and medication-related risk factors were identified including advanced patient age, comorbidities, length of hospital stay, previous hospitalizations, use of probiotic medications and proton pump inhibitors. The review also identified organizational factors such as room size, academic affiliation, and geographic location to be significantly associated with hospital-acquired CDIs. Conclusion Validation of the factors associated with high risk of developing hospital-acquired CDIs identified in this review can aid in the development of risk prediction models to identify patients who are at a higher risk of developing CDIs and developing quality improvement interventions that might improve patient outcomes by minimizing risk of infection.

Background Enterococcus species frequently cause health care–associated bacteremia, with high attributable mortality. The benefit of consultation with infectious disease (ID) specialists has been previously illustrated with Staphylococcus aureus bacteremia. Whether ID consultation (IDC) improves mortality in enterococcal bacteremia is unknown. Methods This is a retrospective cohort single-center study from January 1, 2015, to June 30, 2016, that included all patients >18 years of age admitted with a first episode of Enterococcus bacteremia. Patients were excluded if death or transfer to palliative care occurred within 2 days of positive blood culture. Results Two hundred five patients were included in the study, of whom 64% received IDC. Participants who received IDC were more likely to undergo repeat cultures to ensure clearance (99% vs 74%; P, We report a retrospective cohort study of the effect of infectious diseases consultation (IDC) on thirty-day mortality in patients with Enterococcus bacteremia. We found a 65% decrease in 30-day in-hospital mortality, illustrating that IDC may be essential in improving survival.

Background The Centers for Disease Control and Prevention (CDC) replaced its definition for ventilator-associated pneumonia (VAP) in 2013. The aim of the current study is to compare the outcome of burn patients with ventilator associated events (VAEs). Methods Burn patients with at least two days of ventilator support were identified from the registry between 2013 and 2016. Kruskal-Wallis and Fisher's exact tests were utilized for continuous and categorical variables, respectively. A logistic regression was used for the association between VAE and in-hospital mortality. Results 243 patients were admitted to our burn center, of whom 208 had no VAE, 8 had a VAC, and 27 had an IVAC or PVAP. There was no difference in hospital length of stay, ICU length of stay and ventilator support days between those with no VAE and a VAC. Those with IVAC-plus had significantly worse outcomes compared to patients with no VAEs. Conclusions Burn patients with IVAC-plus had significantly longer hospital and ICU lengths of stay, days on ventilator compared with patients with no VAEs.

Purpose: The present study's objective was to predict the effect of an advanced audiology-led clinic on paediatric ENT outpatient waiting lists in a large secondary public hospital. Methods: A retrospective, single observational study was performed to obtain data on all children referred for semi-urgent or routine ENT outpatient assessment over a six month period. Set criteria were used to calculate the proportion of new ENT referrals that could be eligible for a new advanced audiology-led clinic and the effect this could have on ENT outpatient referrals and capacity. Results: Results indicated that 23% of all semi-urgent and routine paediatric ENT outpatient referrals were eligible for referral to an advanced audiology-led clinic, with 74% of these being from the semi-urgent category. Based on these data, an advanced audiology-led clinic was predicted to increase this facility's ENT outpatient capacity by 77%. Conclusion: In conclusion, the introduction of an advanced audiology-led service could significantly reduce waiting lists and increase capacity in paediatric ENT outpatient services in the public healthcare system.

The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the αENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion of αENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa+)/low potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the γENaC subunit in the PHA-I phenotype. Nephron-specific γENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking αENaC or βEΝaC, an HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase NCC activation. However, when K+ was eliminated from the diet at the time that γENaC was deleted, plasma K+ concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced βENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K+ concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na+ balance in γENaC-deficient mice.

Subtrochanteric fractures are one of the common fractures encountered in general population following a fall due to high velocity injury warranting immediate and active intervention. The main benefit of Proximal Femoral Nailing is being a closed technique offering an excellent reduction at the fracture site and adequate strength for weight bearing even in unstable hip fractures. This intramedullary device is proven to be biomechanically superior to DHS which is an extramedullary device in the treatment of subtrochanteric fractures. The objective of this study is to analyse and evaluate the functional and radiological outcome of subtrochanteric fracture treated with proximal femoral nail. A study population was selected and was carried out with a total of 25 patients (male: 20, female: 5) treated with proximal femoral nail from the year 2015-2016. All the patients were selected based on inclusion criteria such as closed fractures of less than 3 weeks and age above 25. The appropriate selected patients were assessed both clinically and radiologically at regular intervals of 4wks, 8wks, 12wks, 16wks and 20wks. The functional outcome was assessed using Harris Hip score. From our selected study sample we found majority of the patients were unstable fractures (70%) and others were stable fractures (30%). Based on the union, 50% of patients showed full union by 10 to 15 weeks and 35% showed full union by 16 to 20 weeks. We had 95% of the patients with good anatomical results and 50% of the patients with excellent functional results. PFN is a quite safe, well tolerated and effective instrumentation useful in the treatment of all subtrochanteric fractures. Being a closed intramedullary procedure early mobilization and rehabilitation is possible with early restoration of premorbid functions.

OBJECTIVES The National Healthcare Safety Network (NHSN) replaced its old definition for ventilator-associated pneumonia (VAP) with ventilator-associated events (VAEs) in 2013. Little data is available comparing the two definitions in burn patients. METHODS Data from 2011 to 2014 were collected on burn patients mechanically ventilated for at least 2 days. VAP was determined using two methods: (1) pneumonia as defined by the previous more clinical CDC (NHSN) definition captured in the burn registry; (2) pneumonia as defined by the recent CDC (NHSN) standard of VAEs where patients meeting the criteria for possible VAP were considered having a pneumonia. Cohen kappa statistic was measured to compare both definitions, and chi-square and ANOVA to compare admission and clinical outcomes. RESULTS There were 266 burn patients who were mechanically ventilated for at least 2 days between 2011 and 2014. One hundred patients (37.5%) met the criteria by the old definition and 35 (13.1%) met the criteria for both. The kappa statistic was 0.34 (95% confidence interval 0.23-0.45), suggesting weak agreement. Those who met both definitions were mechanically ventilated for a longer period of time (P = 0.0003), and had a longer intensive care unit (ICU) length of stay (LOS) (P = 0.0004) and hospital LOS (P = 0.0014). CONCLUSIONS There is weak agreement between the two definitions of VAP in severely burn patients. However, patients who met both VAP definitions had longer ventilator days, ICU, and hospital stays.

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged 40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to

Balance is an important criterion in assessing health. The lack of exercise of most young people leads to an increased risk of balance abnormity as part of irregular lifestyles. This paper examines the effect of training with an interactive exercise game on young people’s balance after 1 month. The experiment and analysis followed a three-stage design. Initially, gait function testing was conducted to determine a datum point for the situation at the outset; next, a Gym Top balance trainer was used for training; finally, balance was measured with a force plate and center of pressure signals were collected. Differences in balance before and after training were analyzed with multiscale entropy and multivariate multiscale entropy methods. 12 healthy young people were recruited for the experiment. Statistical analysis of the gait test observations revealed that the number of times of standing and sitting increased significantly after training. Multiscale entropy analysis showed that the multiscale entropy curve was higher after training than before training. Multivariate multiscale entropy analysis showed that balance after training was greater than before training. These results demonstrate that the balance of young people was improved after training with a balance trainer eight times a month.

Background The Centers for Disease Control and Prevention's National Healthcare Safety Network (NHSN) replaced its old definition for ventilator-associated pneumonia (VAP) with the ventilator-associated events algorithm in 2013. We sought to compare the outcome of trauma patients meeting the definitions for VAP in the two modules. Methods Trauma patients with blunt or penetrating injuries and with at least 2 d of ventilator support were identified from the trauma registry from 2013 to 2014. VAP was determined using two methods: (1) VAP as defined by the “old,” clinically based NHSN definition and (2) possible VAP as defined by the updated “new” NHSN definition. Cohen's kappa statistic was determined to compare the two definitions for VAP. To compare demographic and clinical outcomes, the chi-square and Student's t-tests were used for categorical and continuous variables, respectively. Results From 2013 to 2014, there were 1165 trauma patients admitted who had at least 2 d of ventilator support. Seventy-eight patients (6.6%) met the “new” NHSN definition for possible VAP, 361 patients (30.9%) met the “old” definition of VAP, and 68 patients (5.8%) met both definitions. The kappa statistic between VAP as defined by the “new” and “old” definitions was 0.22 (95% confidence interval, 0.17-0.27). There were no differences in age, gender, race, or injury severity score when comparing patients who met the different definitions. Those satisfying both definitions had longer ventilator support days (P = 0.0009), intensive care unit length of stay (LOS; P = 0.0003), and hospital LOS (P = 0.0344) when compared with those meeting only one definition. There was no difference in mortality for those meeting both and those meeting the old definition for VAP; patients meeting both definitions had higher respiratory rate at arrival (P = 0.0178). Conclusions There was no difference in mortality between patients meeting the “old” and “new” NHSN definitions for VAP; those who met “both” definitions had longer ventilator support days, intensive care unit, and hospital LOS.

Background: Both metabolic syndrome (MetSyn) and the Renin Angiotensin Aldosterone System (RAAS) are predictors of adverse outcomes in stroke patients. This study aimed at evaluating the association between RAAS and MetSyn among ischaemic stroke subjects in a tertiary hospital of Ghana from September 2015 to June 2016. Methodology: The study purposively recruited 252 Ghanaians comprising 132 ischaemic stroke patients and 120 apparently healthy control subjects. The participants were subjected to measurements of plasma renin, serum aldosterone, lipid profile, anthropometries and blood pressure. Results: MetSyn prevalence among the stroke subjects compared to the controls were 50.0% vs 8.3% (NCEP/ATP III), 71.2% vs 9.2 (IDF) and 71.2% vs 6.7% (H_MS). Both renin and aldosterone were significantly (p 3) aldosterone (aOR = 2.7, p = 0.008), obesity (aOR = 11.7, p = 0.004) and high triglyceride (aOR = 5.3, p p = 0.742) were independently associated with increasing odds of metabolic syndrome. Moreover, there was a significant (p p

WOS: 000485217300010, PubMed ID: 31443932, BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +10.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct., Research Council of NorwayResearch Council of Norway [223273]; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01 MH117601, R01 MH116147, R01 MH111671, P41 EB015922, 5T32MH073526, U54EB020403, R03 MH105808]; National Institute on Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [T32AG058507]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [103703, 106469, 341717]; National Centre for Mental Health; 2010 National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award [17319]; Dokuz Eylul University Department of Scientific Research Projects FundingDokuz Eylul University [2012.KB.SAG.062]; National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London; Ege University School of Medicine Research Foundation [2009-D-00017]; Medical Research CouncilMedical Research Council UK (MRC) [G0901310]; Geestkracht program of the Netherlands Organisation for Health Research and Development [10-000-1002]; National Institute of Mental HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH 085667]; Nova Scotia Health Research Foundation; Dalhousie Clinical Research Scholarship; 2007 Brain and Behavior Research Foundation Young Investigator Award; Ministry of Health of the Czech RepublicMinistry of Health, Czech Republic [NR8786, NT13891]; Swedish Research CouncilSwedish Research Council [K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2, K2012-61X-15078-09-3]; Stockholm County CouncilStockholm County Council; Karolinska InstitutetKarolinska Institutet; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; HUBIN project; Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III [PI070066, PI1100683, PI1500467]; Fundacio Marato TV3 [091630]; ERDF Funds from the European Commission A Way of Making Europe"); Brain and Behaviour Research Foundation (NARSAD Young Investigator Award); Alicia Koplowitz Foundation; Stanley Medical Research Institute; NARSADNARSAD [20244]; Wellcome TrustWellcome Trust [064971, 085475/B/08/Z, 085475/Z/08/Z]; NARSAD Young Investigator AwardNARSAD; European CommunityEuropean Community (EC); NIMH Intramural Research ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH); NIHR Biomedical Research Centre at University College London Hospital; British Medical Association Margaret Temple Fellowship 2016; German Federal Ministry for Education and ResearchFederal Ministry of Education & Research (BMBF) [O1ZX1314B, O1ZX1314G]; Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [1617]; NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01 MH116147, R01 MH113619]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [U01 MH097435, R01 MH084803, R01 EB020062, R01 MH080912, R01 MH052857]; National Science FoundationNational Science Foundation (NSF) [1636893, 1734853]; Australian National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [510135, 1037196, 1063960, 1066177]; ZonMwNetherlands Organization for Health Research and Development [908-02-123]; VIDINetherlands Organization for Scientific Research (NWO) [452-11-014, 917-46-370]; Janssen PharmaceuticaJohnson & Johnson USAJanssen Biotech Inc; Otsuka PharmaceuticalOtsuka Pharmaceutical; Bipolar Disorder Research Network, The researchers and studies included in this article were supported by the Research Council of Norway (Grant No. 223273), National Institutes of Health (NIH) (Grant No. R01 MH117601 [to NJ], Grant Nos. R01 MH116147, R01 MH111671, and P41 EB015922 [to PMT], Grant Nos. 5T32MH073526 and U54EB020403 [to CRKC], and Grant No. R03 MH105808 [to CEB and SCF]) and National Institute on Aging (NIA) (Grant No. T32AG058507 [to CRKC]).; C-SFS: This work was supported by Canadian Institutes of Health Research.; Cardiff: This work was supported by the National Centre for Mental Health, Bipolar Disorder Research Network, 2010 National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (Grant No. 17319).; DEU: This work was supported by Dokuz Eylul University Department of Scientific Research Projects Funding (Grant No. 2012. KB. SAG. 062). This report represents independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, or Department of Health.; EGEU: This work was supported by the Ege University School of Medicine Research Foundation (Grant No. 2009-D-00017).; EHRS: The Edinburgh High Risk Study was supported by the Medical Research Council.; GROUP: The infrastructure for the GROUP study was supported by the Geestkracht program of the Netherlands Organisation for Health Research and Development (Grant No. 10-000-1002).; ENBD_UT/BPO_FLB: This work was supported by the National Institute of Mental Health (Grant No. R01 MH 085667).; HHR/PHHR: This work was supported by the Canadian Institutes of Health Research (Grant Nos. 103703, 106469, and 341717), Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship (to TH), 2007 Brain and Behavior Research Foundation Young Investigator Award (to TH), and Ministry of Health of the Czech Republic (Grant Nos. NR8786 and NT13891).; HUBIN: This work was supported by the Swedish Research Council (Grant Nos. K2007-62X-15077-04-1, K2008-62P-20597-01-3, K2010-62X-15078-07-2, K2012-61X-15078-09-3), regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet, Knut and Alice Wallenberg Foundation, and HUBIN project.; IDIBAPS: This work was supported by the Spanish Ministry of Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI070066, PI1100683, and PI1500467) and Fundacio Marato TV3 (Grant No. 091630), co-financed by ERDF Funds from the European Commission A Way of Making Europe"), Brain and Behaviour Research Foundation (NARSAD Young Investigator Award), and Alicia Koplowitz Foundation.; IoP-BD: The Maudsley Bipolar Twin Study was supported by the Stanley Medical Research Institute and NARSAD.; IoP-SZ: This work was supported by a Wellcome Trust Research Training Fellowship (Grant No. 064971 to MMP), NARSAD Young Investigator Award (to TT), and European Community's Sixth Framework Programme through a Marie Curie Training Network called the European Twin Study Network on Schizophrenia.; Lieber Institute for Brain Development (LIBD): This work was supported by the NIMH Intramural Research Program (to DRW's laboratory). LIBD is a nonprofit research institute located in Baltimore, MD. The work performed at LIBD was performed in accordance with an NIMH material transfer agreement with LIBD.; MFS: The Maudsley Family Study cohort collection was supported by the Wellcome Trust (Grant Nos. 085475/B/08/Z and 085475/Z/08/Z), NIHR Biomedical Research Centre at University College London Hospital, Medical Research Council (Grant No. G0901310), and British Medical Association Margaret Temple Fellowship 2016.; MooDS: This work was supported by the German Federal Ministry for Education and Research grants NGFNplus MooDS (Systematic Investigation of the Molecular Causes of Major Mood Disorders and Schizophrenia) and Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e: Med program (Grant Nos. O1ZX1314B and O1ZX1314G) and Deutsche Forschungsgemeinschaft (Grant No. 1617 [to AH]).; MSSM: This work was supported by NIMH (Grant Nos. R01 MH116147 and R01 MH113619).; NU: This work was supported by NIH (Grant Nos. U01 MH097435, R01 MH084803, and R01 EB020062) and National Science Foundation (Grant Nos. 1636893 and 1734853).; OLIN: This work was supported by NIH (Grant No. R01 MH080912).; STAR: This work was supported by NIH (Grant No. R01 MH052857).; SydneyBipolarGroup: The Australian cohort collection was supported by the Australian National Health and Medical Research Council Program Grants (Grant No. 510135 [to PBM] and Grant No. 1037196 [to PBM and PRS]) and Project Grants (Grant No. 1063960 [to JMF and PRS] and Grant No. 1066177 [to JMF]).; UMCU: This work was supported by NARSAD (Grant No. 20244 [to MHJH]), ZonMw (Grant No. 908-02-123 [to HEHP]), VIDI (Grant No. 452-11-014 [to NEMvH] and Grant No. 917-46-370 [to HEHP]), and Stanley Medical Research Institute.; CliNG: We thank Anna Fanelli, Kathrin Jakob, and Maria Keil for help with data acquisition.; All authors have contributed to and approved the contents of this manuscript.; GS has received research and travel support from Janssen Pharmaceutica and Otsuka Pharmaceutical and honoraria from Adamed Pharma. NY has been an investigator in clinical studies conducted together with Janssen-Cilag, Corcept Therapeutics, and COMPASS Pathways in the last 3 years. AM-L has received consultant fees from Boehringer Ingelheim, BrainsWay, Elsevier, Lundbeck International Neuroscience Foundation, and Science Advances. CRKC has received partial research support from Biogen, Inc. (Boston, MA) for work unrelated to the topic of this manuscript. The remaining authors report no biomedical financial interests or potential conflicts of interest.

The development of a health evaluation system from human-related data is an important issue in preventive medicine. Previously, most studies have focused on disease assessment and prevention in patients. However, even if certain risk factors are all within normal ranges, individuals may not necessarily be completely healthy. This study focused on healthy individuals to develop a new index to assess health risks, this index can be used for the prevention of multiple diseases in healthy people. The kernel density technique was proposed to estimate the distribution of common risk factors and to develop a health risk index. A dataset of hypertension, hyperlipidemia, and hyperglycemia (Triple H) data from the National Health Insurance Research Database in Taiwan was used to demonstrate the proposed analytical process. The results of risk factor changes after six weeks of exercise were used to calculate the health risk index. The results showed that the subjects experienced a 7.29% reduction in their health risk index after the exercise intervention. This finding demonstrates the potential impact of an important reference index on quantifying the effect of maintenance in healthy people.

A key factor for fall prevention involves understanding the pathophysiology of stability. This study proposes the postural stability index (PSI), which is a novel measure to quantify different stability states on healthy subjects. The results of the x-, y-, and z-axes of the acceleration signals were analyzed from 10 healthy young adults and 10 healthy older adults under three conditions as follows: Normal walking, walking with obstacles, and fall-like motions. The ensemble empirical mode decomposition (EEMD) was used to reconstruct the acceleration signal data. Wearable accelerometers were located on the ankles and knees of the subjects. The PSI indicated a decreasing trend of its values from normal walking to the fall-like motions. Free-walking data were used to determine the stability based on the PSI. The segmented free-walking data indicated changes in the stability states that suggested that the PSI is potentially helpful in quantifying gait stability.

It is poorly understood how healthy aging affects neural mechanisms underlying motor learning. We used blood-oxygen-level dependent (BOLD) contrasts to examine age-related changes in brain activation after acquisition and consolidation (24 h) of a visuomotor tracking skill. Additionally, structural magnetic resonance imaging and diffusion tensor imaging were used to examine age-related structural changes in the brain. Older adults had reduced gray matter volume (628 ± 57 ml) and mean white matter anisotropy (0.18 ± 0.03) compared with young adults (741 ± 59 ml and 0.22 ± 0.02, respectively). Although motor performance was 53% lower in older (n = 15, mean age 63.1 years) compared with young adults (n = 15, mean age 25.5 years), motor practice improved motor performance similarly in both age groups. While executing the task, older adults showed in general greater brain activation compared with young adults. BOLD activation decreased in parietal and occipital areas after skill acquisition but activation increased in these areas after consolidation in both age groups, indicating more efficient visuospatial processing immediately after skill acquisition. Changes in deactivation in specific areas were age-dependent after consolidating the motor skill into motor memory. Young adults showed greater deactivations from post-test to retention in parietal, occipital and temporal cortices, whereas older adults showed smaller deactivation in the frontal cortex. Since learning rate was similar between age groups, age-related changes in activation patterns may be interpreted as a compensatory mechanism for age-related structural decline.

Highlights • Connectivity analyses complemented with a metric exploring switching in brain activity. • Lower insula-salience connectivity predicts insufficient antidepressant response. • This same insula region is activated less when switching from task to a rest. • This could be a potential biomarkers for predicting future antidepressant response., Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.

Summary Background In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017–18 human monkeypox outbreak in Nigeria. Methods We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. Findings 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. Interpretation This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. Funding None.

Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. (C) 2016 Published by Elsevier Ltd.

Home parenteral nutrition (HPN) is increasingly used for nutrition support after patients are discharged from the hospital. Catheter-related bloodstream infections (CR-BSI) are a common and potentially fatal complication of HPN. The risk factors for development of CR-BSI in the outpatient setting are poorly understood.We conducted an observational, retrospective study of 225 patients discharged from Barnes-Jewish Hospital on HPN between January 1, 2007, and December 31, 2009. HPN complications were defined as any cause that led to either premature discontinuation of HPN therapy or catheter replacement. CR-BSI events were identified by provider documentation. We calculated the overall complication rate and the complication rate specifically due to CR-BSI. Backward stepwise Cox regression analyses were used to assess for independent predictors of catheter-related complications.In total, 111 of 225 patients (49%) developed complications while receiving HPN (incidence = 5.06 episodes/1000 catheter days). Sixty-eight of 225 patients (30%) required catheter removal for CR-BSI (incidence = 3.10 episodes/1000 catheter days). Independent predictors of line removal specifically due to infection included anticoagulant use, ulcer or open wound, and Medicare or Medicaid insurance. The following risk factors were associated with catheter-associated complications and/or CR-BSI: the presence of ulcers, the use of systemic anticoagulants, public insurance (Medicare or Medicaid), and patient age. Independent predictors of line removal for any complication included age and anticoagulant use.Catheter-related complications were extremely common in patients receiving HPN. Healthcare providers caring for individuals who require HPN should be aware of risk factors for complications.

Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.

ObjectivesTo assess the role of brain networks in emotion regulation and post-traumatic complaints in the sub-acute phase after non-complicated mild traumatic brain injury (mTBI). Experimental designFifty-four patients with mTBI (34 with and 20 without complaints) and 20 healthy controls (group-matched for age, sex, education, and handedness) were included. Resting-state fMRI was performed at four weeks post-injury. Static and dynamic functional connectivity were studied within and between the default mode, executive (frontoparietal and bilateral frontal network), and salience network. The hospital anxiety and depression scale (HADS) was used to measure anxiety (HADS-A) and depression (HADS-D). Principal ObservationsRegarding within-network functional connectivity, none of the selected brain networks were different between groups. Regarding between-network interactions, patients with complaints exhibited lower functional connectivity between the bilateral frontal and salience network compared to patients without complaints. In the total patient group, higher HADS-D scores were related to lower functional connectivity between the bilateral frontal network and both the right frontoparietal and salience network, and to higher connectivity between the right frontoparietal and salience network. Furthermore, whereas higher HADS-D scores were associated with lower connectivity within the parietal midline areas of the bilateral frontal network, higher HADS-A scores were related to lower connectivity within medial prefrontal areas of the bilateral frontal network. ConclusionsFunctional interactions of the executive and salience networks were related to emotion regulation and complaints after mTBI, with a key role for the bilateral frontal network. These findings may have implications for future studies on the effect of psychological interventions. Hum Brain Mapp 37:1645-1654, 2016. (c) 2016 Wiley Periodicals, Inc.

Background: One of the major risk factors for cardiovascular diseases is lipid abnormalities. Objective: To determine the mean lipid levels and the prevalence of lipid disorders among patients attending outpatient clinics in Banjul, The Gambia. Design: Cro...