Asymptomatic individuals can increase the final epidemic size under adaptive human behavior.

Infections produced by non-symptomatic (pre-symptomatic and asymptomatic) individuals have been identified as major drivers of COVID-19 transmission. Non-symptomatic individuals, unaware of the infection risk they pose to others, may perceive themselves-and be perceived by others-as not presenting a risk of infection. Yet, many epidemiological models currently in use do not include a behavioral component, and do not address the potential consequences of risk misperception. To study the impact of behavioral adaptations to the perceived infection risk, we use a mathematical model that incorporates the behavioral decisions of individuals, based on a projection of the system's future state over a finite planning horizon. We found that individuals' risk misperception in the presence of non-symptomatic individuals may increase or reduce the final epidemic size. Moreover, under behavioral response the impact of non-symptomatic infections is modulated by symptomatic individuals' behavior. Finally, we found that there is an optimal planning horizon that minimizes the final epidemic size.

Predicting subclinical psychotic-like experiences on a continuum using machine learning.

Previous studies applying machine learning methods to psychosis have primarily been concerned with the binary classification of chronic schizophrenia patients and healthy controls. The aim of this study was to use electroencephalographic (EEG) data and pattern recognition to predict subclinical psychotic-like experiences on a continuum between these two extremes in otherwise healthy people. We applied two different approaches to an auditory oddball regularity learning task obtained from N = 73 participants: A feature extraction and selection routine incorporating behavioural measures, event-related potential components and effective connectivity parameters; Regularisation of spatiotemporal maps of event-related potentials. Using the latter approach, optimal performance was achieved using the response to frequent, predictable sounds. Features within the P50 and P200 time windows had the greatest contribution toward lower Prodromal Questionnaire (PQ) scores and the N100 time window contributed most to higher PQ scores. As a proof-of-concept, these findings demonstrate that EEG data alone are predictive of individual psychotic-like experiences in healthy people. Our findings are in keeping with the mounting evidence for altered sensory responses in schizophrenia, as well as the notion that psychosis may exist on a continuum expanding into the non-clinical population.

Identifying Preclinical Alzheimer's Disease Using Everyday Driving Behavior: Proof of Concept.

We examined whether driving behavior can predict preclinical Alzheimer's disease (AD). Data from 131 cognitively normal older adults with cerebrospinal fluid (CSF) and/or positron emission tomography (PET) biomarkers were examined with naturalistic driving behavior. Receiver operating characteristic curves were used to predict the highest 10%, 25%, and 50% of values for CSF tau/Aß42, ptau181/Aß42, or amyloid PET. Six in vivo driving variables alone yielded area under the curves (AUC) from 0.64-0.82. Addition of age, Apolipoprotein ɛ4, and neuropsychological measures to the models improved the AUC (0.81 to 0.90). Driving can be used as novel neurobehavioral marker to identify presence of preclinical AD.

Silent cerebral infarcts in patients with sickle cell disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Silent cerebral infarcts (SCIs) are the most common neurological complication in children and adults with sickle cell disease (SCD). In this systematic review, we provide an overview of studies that have detected SCIs in patients with SCD by cerebral magnetic resonance imaging (MRI). We focus on the frequency of SCIs, the risk factors involved in their development and their clinical consequences. METHODS: The databases of Embase, MEDLINE ALL via Ovid, Web of Science Core Collection, Cochrane Central Register of Trials via Wiley and Google Scholar were searched from inception to June 1, 2019. RESULTS: The search yielded 651 results of which 69 studies met the eligibility criteria. The prevalence of SCIs in patients with SCD ranges from 5.6 to 80.6% with most studies reported in the 20 to 50% range. The pooled prevalence of SCIs in HbSS and HbSß0 SCD patients is 29.5%. SCIs occur more often in patients with the HbSS and HbSß0 genotype in comparison with other SCD genotypes, as SCIs are found in 9.2% of HbSC and HbSß+ patients. Control subjects showed a mean pooled prevalence of SCIs of 9.8%. Data from included studies showed a statistically significant association between increasing mean age of the study population and mean SCI prevalence. Thirty-three studies examined the risk factors for SCIs. The majority of the risk factors show no clear association with prevalence, since more or less equal numbers of studies give evidence for and against the causal association. CONCLUSIONS: This systematic review and meta-analysis shows SCIs are common in patients with SCD. No clear risk factors for their development were identified. Larger, prospective and controlled clinical, neuropsychological and neuroimaging studies are needed to understand how SCD and SCIs affect cognition.

Clinical characteristics and online mental health care of asymptomatic or mildly symptomatic patients with coronavirus disease 2019.

Comparing to data in patients with severe coronavirus diseases 2019 (COVID-19), there are few studies on the prevalence anxiety and/or depression in patients with asymptomatic or mildly symptomatic COVID-19. We investigated the clinical characteristics and the prevalence of anxiety and/or depression among asymptomatic or mildly symptomatic patients with COVID-19 and monitored their mental health using an online assessment. An online survey for monitoring and assessing the mental health of patients with COVID-19 using a mobile phone was conducted. We used the Hospital Anxiety and Depression Scale to measure anxiety and/or depression levels. Of the 234 patients, 66 patients were asymptomatic (28.2%), while the remaining 168 patients were mildly symptomatic. The prevalence of anosmia (p = 0.001) and ageusia (p = 0.008) significantly decreased with the increasing age. In addition, 19.8% and 14.0% patients had anxiety and/or depression in the first survey, and one week after the first survey, respectively. Compared to patients without anxiety and/or depression, those with anxiety and/or depression had a longer quarantine duration. We found that anomia and ageusia were relatively common in the young age group. Furthermore, one-fifth asymptomatic or mildly symptomatic patients with COVID-19 had anxiety and/or depression.

Psychological Wellbeing and Aortic Stiffness: Longitudinal Study.

This study investigated 2 distinct aspects of positive wellbeing: affective wellbeing and eudaimonia with progression of aortic stiffness, an index of subclinical cardiovascular disease. A total of 4754 participants (mean age 65.3 years, 3466 men, and 1288 women) from the Whitehall II cohort study provided data on affective and eudaimonic wellbeing using subscales from the control, autonomy, self-realization and pleasure-19 questionnaire. Aortic stiffness was measured by aortic pulse wave velocity (PWV) at baseline (2008-2009) and 5 years later (2012-2013). Linear mixed models were used to measure the effect of affective and eudaimonic wellbeing on baseline PWV and 5-year PWV longitudinal change. A 1-SD higher eudaimonic wellbeing was associated with lower baseline PWV in men (ß=-0.100 m/s [95% CI=-0.169 to -0.032]), independent of social, behavioral, and biological factors. This association persisted over 5 years. No such association was found in women (ß=-0.029 m/s [95% CI=-0.126 to 0.069]). We did not find any association of positive wellbeing with change in PWV over time in either men or women. In older men, higher levels of eudaimonic wellbeing were associated with lower long-term levels of arterial stiffness. These findings support the notion that the pattern of association between positive wellbeing and cardiovascular health outcomes involves eudaimonic rather than affective wellbeing and is sex-specific.

Hypothesized behavioral host manipulation by SARS-CoV2/COVID-19 infection.

Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host's central nervous system and triggers hyper aggression. The virus is also present in the rabid animal's saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.

[Religious-spiritual crisis or psychosis? The impact of basic symptoms in the differentiation of prepsychotic states].

Religious-spiritual crises include distress associated with the weakening or loss of faith, turbulent conversions, and affective states associated with negative spirituality. The differential diagnosis in regard to psychosis is often challenging. The purpose of the present study was to investigate the role of basic symptoms (changes in the subjective experience of perception, thinking, feeling, and self) in the differential diagnosis. We evaluated 106 help-seeking individuals with the Bonn Scale for the Assessment of Basic Symptoms (BSABS). The results indicated that religiousspiritual crises and psychotic states could be properly differentiated with the BSABS. Although the crisis and psychosis groups scored similarly on perplexity, self-disorder, depression, and anxiety, the disturbance of social contact and cognition was observed only in psychosis. These results indicate that the assessment of basic symptoms is useful in the differentiation of religious-spiritual crisis and psychosis, but it does not replace a multidisciplinary approach when, in addition to the routine psychiatric examination, the wider cultural context and the personal narratives are also considered.

Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany.

IMPORTANCE: Public health screening for type 1 diabetes in its presymptomatic stages may reduce disease severity and burden on a population level. OBJECTIVE: To determine the prevalence of presymptomatic type 1 diabetes in children participating in a public health screening program for islet autoantibodies and the risk for progression to clinical diabetes. DESIGN, SETTING, AND PARTICIPANTS: Screening for islet autoantibodies was offered to children aged 1.75 to 5.99 years in Bavaria, Germany, between 2015 and 2019 by primary care pediatricians during well-baby visits. Families of children with multiple islet autoantibodies (presymptomatic type 1 diabetes) were invited to participate in a program of diabetes education, metabolic staging, assessment of psychological stress associated with diagnosis, and prospective follow-up for progression to clinical diabetes until July 31, 2019. EXPOSURES: Measurement of islet autoantibodies. MAIN OUTCOMES AND MEASURES: The primary outcome was presymptomatic type 1 diabetes, defined by 2 or more islet autoantibodies, with categorization into stages 1 (normoglycemia), 2 (dysglycemia), or 3 (clinical) type 1 diabetes. Secondary outcomes were the frequency of diabetic ketoacidosis and parental psychological stress, assessed by the Patient Health Questionnaire-9 (range, 0-27; higher scores indicate worse depression; ≤4 indicates no to minimal depression; >20 indicates severe depression). RESULTS: Of 90 632 children screened (median [interquartile range {IQR}] age, 3.1 [2.1-4.2] years; 48.5% girls), 280 (0.31%; 95% CI, 0.27-0.35) had presymptomatic type 1 diabetes, including 196 (0.22%) with stage 1, 17 (0.02%) with stage 2, 26 (0.03%) with stage 3, and 41 who were not staged. After a median (IQR) follow-up of 2.4 (1.0-3.2) years, another 36 children developed stage 3 type 1 diabetes. The 3-year cumulative risk for stage 3 type 1 diabetes in the 280 children with presymptomatic type 1 diabetes was 24.9% ([95% CI, 18.5%-30.7%]; 54 cases; annualized rate, 9.0%). Two children had diabetic ketoacidosis. Median (IQR) psychological stress scores were significantly increased at the time of metabolic staging in mothers of children with presymptomatic type 1 diabetes (3 [1-7]) compared with mothers of children without islet autoantibodies (2 [1-4]) (P = .002), but declined after 12 months of follow-up (2 [0-4]) (P < .001). CONCLUSIONS AND RELEVANCE: Among children aged 2 to 5 years in Bavaria, Germany, a program of primary care-based screening showed an islet autoantibody prevalence of 0.31%. These findings may inform considerations of population-based screening of children for islet autoantibodies.

I Would Never Take Preventive Medication! Perspectives and Information Needs of People Who Underwent Predictive Tests for Rheumatoid Arthritis.

OBJECTIVE: Little is known about the experiences, values, and needs of people without arthritis who undergo predictive biomarker testing for the development of rheumatoid arthritis (RA). Our study aimed to explore the perspectives of these individuals and describe their information needs. METHODS: A qualitative, multicenter interview study with a thematic analysis was conducted in Austria, Germany and the UK. Individuals were interviewed who underwent predictive biomarker testing for RA and had a positive test result but no diagnosis of any inflammatory joint disease. Participants included patients with arthralgia and asymptomatic individuals. Information and education needs were developed from the qualitative codes and themes using the Arthritis Educational Needs Assessment Tool as a frame of reference. RESULTS: Thematic saturation was reached in 34 individuals (76% female, 24 [71%] with arthralgia, and 10 [29%] asymptomatic individuals). Thirty-seven codes were summarized into 4 themes: 1) decision-making around whether to undergo initial predictive testing, 2) willingness to consider further predictive tests, and/or 3) preventive interventions, including medication, and 4) varying reactions after receiving a positive test result. Individuals with arthralgia were more likely to be willing to take preventive action, undergo further testing, and experience psychological distress than asymptomatic individuals. All participants expressed the need for tailored, patient-understandable information. CONCLUSION: Individuals at risk of RA are currently the subjects of research aimed at developing better predictive strategies and preventive approaches. Their perceptions and needs should be addressed to inform the future development of interventions combined with education.

ART adherence and viral suppression are high among most non-pregnant individuals with early-stage, asymptomatic HIV infection: an observational study from Uganda and South Africa.

INTRODUCTION: The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS-free generation depend on high adherence in individuals initiating ART during early-stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. METHODS: From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non-pregnant women with early-stage HIV infection (CD4 > 350 cells/µL), pregnant women with early-stage HIV infection and men and non-pregnant women with late-stage HIV infection (CD4 < 200 cells/µL). Socio-behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically. RESULTS: Adherence data were available for 869 participants: 322 (37%) early/non-pregnant, 199 (23%) early/pregnant and 348 (40%) late/non-pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non-pregnant versus early/pregnant or late/non-pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non-pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking. DISCUSSION: ART adherence among non-pregnant individuals with early-stage infection is as high or higher than with late-stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late-stage infection in South Africa and highlight the need for differentiated care delivery.

Valuing biomarker diagnostics for dementia care: enhancing the reflection of patients, their care-givers and members of the wider public.

What is the value of an early (presymptomatic) diagnosis of dementia in the absence of effective treatment? There has been a lively scholarly debate over this question, but until now (future) patients have not played a large role in it. Our study supplements biomedical research into innovative diagnostics with an exlporation of its meanings and values according to (future) patients. Based on seven focusgroups with (future) patients and their care-givers, we conclude that stakeholders evaluate early diagnostics with respect to whether and how they expect it to empower their capacity to (self-) care. They value it, for instance, with respect to whether it (a) explains experienced complaints, (b) allows to start a process of psychological acceptance and social adaptation to the expected degeneration, (c) contributes to dealing with anxieties (with respect to inheritable versions of dementia), (d) informs adequately about when to start preparing for the end of life, (d) informs the planning of a request for euthanasia, or (e) allows society to deal with a growing amount of dementia patients. Our study suggests that information about disease is considered 'harmful' or 'premature' when recipients feel unable to act on that information in their (self-) care. The results of this research offers input to further ethical research. It invites to adopt a care perspective in evaluation and to seek ways to prevent the 'harm' that such diagnostic methods can bring about.

Risk perception before and after presymptomatic genetic testing for Huntington's disease: Not always what one might expect.

BACKGROUND: In 1983, Huntington's disease (HD) was the first genetic disease mapped using DNA polymorphisms. Shortly thereafter, presymptomatic genetic testing for HD began in the context of two research studies. One of these trials was at the Johns Hopkins University Huntington's Disease Center. METHODS: As part of the protocol, risk perception (RP) values were collected at 16 time points before and after testing. The current study investigated changes in RP scores before and after genetic testing. Of the 186 participants with pre- and post-testing RP values, 39 also had contemporaneous research clinic notes and recent semi-structured interviews available for analysis. RESULTS: The data reveal tremendous diversity in RP. While the RP scores of most individuals change in the way one would expect, 27% of participants demonstrated unexpected changes in RP after disclosure. A significantly higher proportion of individuals who received an expanded repeat result had unexpected changes in RP, compared with those who received normal repeat results. CONCLUSIONS: The data suggest that individuals' RP is influenced by more than merely the results of genetic testing. This finding is important for genetic counselors and healthcare providers, as it suggests that even comprehensive patient education and disclosure of genetic test results may not ensure that people fully appreciate their disease risk.

Cross-cultural adaptation of Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score: Reliability and validity in Turkish-speaking overhead athletes.

OBJECTIVE: Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score (KJOC-SES) is a subjective assessment tool to measure functional status of the upper extremities in overhead athletes. The aim was to translate and culturally adapt the KJOC-SES and to evaluate the psychometric properties of the Turkish version (KJOC-SES-Tr) in overhead athletes. METHODS: The forward and back-translation method was followed. One hundred and twenty-three overhead athletes completed the KJOC-SES-Tr, the Disabilities of the Arm, Shoulder, and Hand (DASH), and the American Shoulder and Elbow Surgeons Evaluation Form (ASES). Participants were assigned to one of the following subgroups: asymptomatic (playing without pain) or symptomatic (playing with pain, or not playing due to pain). Internal consistency, reliability, construct validity, discriminant validity, and content validity of the KJOC-SES-Tr were tested. RESULTS: The test-retest reliability of the KJOC-SES-Tr was excellent with an interclass coefficient of 0.93. There was a strong correlation between the KJOC-SES-Tr and the DASH and the ASES, indicating that the construct validity was good for all participants. Results of the KJOC-SES-Tr significantly differed between different subgroups and categories of athletes. The floor and ceiling effects were acceptable for symptomatic athletes. CONCLUSION: The KJOC-SES-Tr was shown to be valid, reliable tool to monitor the return to sports following injuries in athletes.

Neuropsychological performance in patients with asymptomatic HIV-1 infection.

Human immunodeficiency virus (HIV-1) infection and acquired immunodeficiency syndrome (AIDS) lead to neurocognitive disorders; however, there is still much knowledge to be gained regarding HIV-associated neurocognitive disorders. The purpose of this study was to assess the cognitive performance, instrumental activities of daily living, depression, and anxiety in patients with asymptomatic HIV-1 infections compared with seronegative participants without neurocognitive impairment. We studied a sample consisted of 60 patients with asymptomatic HIV-1 infections and 60 seronegative participants without neurocognitive impairment from the city of Barranquilla, Colombia, with a mean age of 36.07 years. A protocol of neuropsychological and psychopathological tests was applied to the participants. The group of patients with asymptomatic HIV infections significantly underperformed on tasks that assessed global cognitive screening, attention span, learning, phonemic verbal fluency, auditory-verbal comprehension, information processing speed, cognitive flexibility, and motor skills compared to the group of seronegative participants. No significant differences were found in memory, visual confrontation naming, vocabulary, inhibition, and instrumental activities of daily living. Additionally, the patients with asymptomatic HIV-1 infection had a higher anxiety index than the seronegative participants, but no significant difference was found in depression. A correlation was found between depression and anxiety. In conclusion, the patients with asymptomatic HIV-1 infection had lower cognitive performances than the seronegative participants in the cognitive functions mentioned above and more anxiety but still performed the instrumental activities of daily living.

Experimental Low Back Pain Decreased Trunk Muscle Activity in Currently Asymptomatic Recurrent Low Back Pain Patients During Step Tasks.

Low back pain (LBP) patients show reorganized trunk muscle activity but if similar changes are manifest in recurrent LBP (R-LBP) patients during asymptomatic periods remains unknown. In 26 healthy and 27 currently asymptomatic R-LBP participants electromyographic activity (EMG) was recorded from trunk and gluteal muscles during series of stepping up and down on a step bench before and during experimentally intramuscular induced unilateral and bilateral LBP. Pain intensity was assessed using numeric rating scale (NRS) scores. Root mean square EMG (RMS-EMG) normalized to maximal voluntary contraction EMG and pain-evoked differences from baseline (ΔRMS-EMG) were analyzed. Step task duration was calculated from foot sensors. R-LBP compared with controls showed higher baseline RMS-EMG and NRS scores of experimental pain (P < .05). In both groups, bilateral compared with unilateral experimental NRS scores were higher (P < .001) and patients compared with controls reported higher NRS scores during both pain conditions (P < .04). In patients, unilateral pain decreased ΔRMS-EMG in the Iliocostalis muscle and bilateral pain decreased ΔRMS-EMG in all back and gluteal muscles during step tasks (P < .05) compared with controls. In controls, bilateral versus unilateral experimental pain induced increased step task duration and trunk RMS-EMG whereas both pain conditions decreased step task duration and trunk RMS-EMG in R-LBP patients compared with controls (P < .05). PERSPECTIVE: Task duration and trunk muscle activity increased in controls and decreased in R-LBP patients during experimental muscle LBP. These results indicate protective strategies in controls during acute pain whereas R-LBP patients showed higher pain intensity and altered strategies that may be caused by the higher pain intensity, but the long-term consequence remains unknown.

Can We Predict and Prevent Subclinical Depression in Adolescents?

The purposes of this article were to determine which risk factors are significant predictors of the occurrence of depression in adolescence and to discriminate among clinical, subclinical, and control groups. The sample consisted of 412 adolescents (61.7% female, 38.3% male) aged 13 to 17 years. Cognitive vulnerability factors for depression (i.e., dysfunctional attitudes, negative inferential style, ruminative response style) and psychosocial risk factors (i.e., negative life events, perceived social support) were measured. Subsequent discriminant function analysis indicated that it was possible to distinguish groups on the basis of the mentioned predictors, and it allocated two discriminant functions (significant at p < 0.001). Unexpectedly, ruminative response style was the most powerful discriminative predictor possessing a positive and adaptive part, and, at the same time, it maximally distinguished the subclinical group from the clinical and control groups.

A Population-Based Longitudinal Study of Symptoms and Signs Before the Onset of Psychosis.

OBJECTIVE: The authors sought to characterize the symptoms of patients later hospitalized for psychotic disorders in primary mental health outpatient settings, and to investigate whether these symptoms can be used to predict later onset of psychotic illness. METHOD: This was a population-based historical prospective cohort study using national registers of clinical psychiatric services. The sample (N=114,983) comprised 18- to 21-year-olds serving in the Israeli military and examined in military mental health outpatient clinics across 72 consecutive months. RESULTS: Overall, 1,092 individuals (0.95%) not diagnosed with a psychotic disorder at the time of examination were hospitalized for nonaffective psychotic disorder up to 9 years after the index examination. A principal components analysis of symptoms presented at index examination found that a symptom cluster of thought disorder, perceptual abnormalities, poor orientation, and suicidality was associated with an increased risk for hospitalization for nonaffective psychotic disorder within 14 days after examination (hazard ratio=45.80, 95% CI=22.87-91.73), 15-111 days after examination, (hazard ratio=19.59, 95% CI=13.08-29.33), 112-365 days after examination (hazard ratio=4.94, 95% CI=2.59-9.40), and 1-3.5 years after examination (hazard ratio=3.42, 95% CI=2.21-5.28), but not for hospitalization 3.5 years or more after examination (hazard ratio=1.57, 95% CI=0.91-2.71). Despite the increased risk, the positive predictive values of this symptom cluster were low, ranging from 0.54% to 1.99%. CONCLUSIONS: In 18- to 21-year-olds, the presence of psychotic symptoms was associated with later hospitalization for a nonaffective psychotic disorder. However, the low positive predictive values of symptoms elicited in primary mental health care settings suggest that symptoms alone are not useful in predicting later hospitalization for nonaffective psychotic disorder.