Sensitivity of contact-tracing for COVID-19 in Thailand: a capture-recapture application.

BACKGROUND: We investigate the completeness of contact tracing for COVID-19 during the first wave of the COVID-19 pandemic in Thailand, from early January 2020 to 30 June 2020. METHODS: Uni-list capture-recapture models were applied to the frequency distributions of index cases to inform two questions: (1) the unobserved number of index cases with contacts, and (2) the unobserved number of index cases with secondary cases among their contacts. RESULTS: Generalized linear models (using Poisson and logistic families) did not return any significant predictor (age, sex, nationality, number of contacts per case) on the risk of transmission and hence capture-recapture models did not adjust for observed heterogeneity. Best fitting models, a zero truncated negative binomial for question 1 and zero-truncated Poisson for question 2, returned sensitivity estimates for contact tracing performance of 77.6% (95% CI = 73.75-81.54%) and 67.6% (95% CI = 53.84-81.38%), respectively. A zero-inflated negative binomial model on the distribution of index cases with secondary cases allowed the estimation of the effective reproduction number at 0.14 (95% CI = 0.09-0.22), and the overdispersion parameter at 0.1. CONCLUSION: Completeness of COVID-19 contact tracing in Thailand during the first wave appeared moderate, with around 67% of infectious transmission chains detected. Overdispersion was present suggesting that most of the index cases did not result in infectious transmission chains and the majority of transmission events stemmed from a small proportion of index cases.

Extending the Lincoln-Petersen estimator for multiple identifications in one source.

The Lincoln-Petersen estimator is one of the most popular estimators used in capture-recapture studies. It was developed for a sampling situation in which two sources independently identify members of a target population. For each of the two sources, it is determined if a unit of the target population is identified or not. This leads to a 2 × 2 table with frequencies f11 ,f10 ,f01 ,f00 indicating the number of units identified by both sources, by the first but not the second source, by the second but not the first source and not identified by any of the two sources, respectively. However, f00 is unobserved so that the 2 × 2 table is incomplete and the Lincoln-Petersen estimator provides an estimate for f00 . In this paper, we consider a generalization of this situation for which one source provides not only a binary identification outcome but also a count outcome of how many times a unit has been identified. Using a truncated Poisson count model, truncating multiple identifications larger than two, we propose a maximum likelihood estimator of the Poisson parameter and, ultimately, of the population size. This estimator shows benefits, in comparison with Lincoln-Petersen's, in terms of bias and efficiency. It is possible to test the homogeneity assumption that is not testable in the Lincoln-Petersen framework. The approach is applied to surveillance data on syphilis from Izmir, Turkey.

Assessing injury risk in male and female Royal Navy recruits: does the Functional Movement Screen provide understanding to inform effective injury mitigation?

INTRODUCTION: Musculoskeletal injuries (MSKIs) are common during military and other occupational physical training programmes, and employers have a duty of care to mitigate this injury risk. MSKIs account for a high number of working days lost during initial military training, contribute to training attrition and impact training costs. Poorer movement quality may be associated with increased MSKI risk. METHODS: The present study evaluated the relationship between the Functional Movement Screen (FMS) Score, as a measure of movement quality, and injury risk in Royal Navy (RN) recruits. A cohort of 957 recruits was assessed using the FMS prior to the 10-week phase I training programme. Injury occurrence, time, type and severity were recorded prospectively during the training period. RESULTS: Total FMS Score was associated with injury risk (p≤0.001), where recruits scoring ≥13 were 2.6 times more likely to sustain an injury during training. However, FMS Score accounted for only 10% of the variance in injury risk (R2=0.1). Sex was the only additional variable to significantly affect the regression model. Mean FMS Scores for men (14.6±2.3) and women (14.4±2.4) were similar, but injury occurrence in women was 1.7 times greater than in men. Examining the influence of individual FMS movement tests on injury prediction did not improve the model, where those movements that significantly contributed to injury prediction only accounted for a small amount of the variance (R2=0.01). CONCLUSION: There was a weak relationship between FMS and injury risk in RN recruits. Evidence is provided that FMS score alone would not be appropriate to use as an injury prediction tool in military recruits.

Application of one-list capture-recapture models to scrapie surveillance data in Great Britain.

In this paper, we apply one-list capture-recapture models to estimate the number of scrapie-affected holdings in Great Britain. We applied this technique to the Compulsory Scrapie Flocks Scheme dataset where cases from all the surveillance sources monitoring the presence of scrapie in Great Britain, the abattoir survey, the fallen stock survey and the statutory reporting of clinical cases, are gathered. Consequently, the estimates of prevalence obtained from this scheme should be comprehensive and cover all the different presentations of the disease captured individually by the surveillance sources. Two estimators were applied under the one-list approach: the Zelterman estimator and Chao's lower bound estimator. Our results could only inform with confidence the scrapie-affected holding population with clinical disease; this moved around the figure of 350 holdings in Great Britain for the period under study, April 2005-April 2006. Our models allowed the stratification by surveillance source and the input of covariate information, holding size and country of origin. None of the covariates appear to inform the model significantly.

Meta-analysis: a unifying meta-likelihood approach framing unobserved heterogeneity, study covariates, publication bias, and study quality.

OBJECTIVES: This contribution provides a unifying concept for meta-analysis integrating the handling of unobserved heterogeneity, study covariates, publication bias and study quality. It is important to consider these issues simultaneously to avoid the occurrence of artifacts, and a method for doing so is suggested here. METHODS: The approach is based upon the meta-likelihood in combination with a general linear nonparametric mixed model, which lays the ground for all inferential conclusions suggested here. RESULTS: The concept is illustrated at hand of a meta-analysis investigating the relationship of hormone replacement therapy and breast cancer. The phenomenon of interest has been investigated in many studies for a considerable time and different results were reported. In 1992 a meta-analysis by Sillero-Arenas et al. concluded a small, but significant overall effect of 1.06 on the relative risk scale. Using the meta-likelihood approach it is demonstrated here that this meta-analysis is due to considerable unobserved heterogeneity. Furthermore, it is shown that new methods are available to model this heterogeneity successfully. It is argued further to include available study covariates to explain this heterogeneity in the meta-analysis at hand. CONCLUSIONS: The topic of HRT and breast cancer has again very recently become an issue of public debate, when results of a large trial investigating the health effects of hormone replacement therapy were published indicating an increased risk for breast cancer (risk ratio of 1.26). Using an adequate regression model in the previously published meta-analysis an adjusted estimate of effect of 1.14 can be given which is considerably higher than the one published in the meta-analysis of Sillero-Arenas et al. In summary, it is hoped that the method suggested here contributes further to a good meta-analytic practice in public health and clinical disciplines.

Youden's Index and the Likelihood Ratio Positive in Diagnostic Testing.

We refer to a recent letter to the editor by Hughes and show that, despite existing similarities between Youden's index and the log-likelihood ratio positive, important differences between these two measures remain to exist which can play an important difference in clinical practice.

A combined TMS/fMRI study of intensity-dependent TMS over motor cortex.

BACKGROUND: Transcranial magnetic stimulation (TMS) allows noninvasive stimulation of neurons using time-varying magnetic fields. Researchers have begun combining TMS with functional imaging to simultaneously stimulate and image brain activity. Recently, the feasibility of interleaving TMS with functional magnetic resonance imaging (fMRI) was demonstrated. This study tests this new method to determine if TMS at different intensities shows different local and remote activation. METHODS: Within a 1.5 Tesla (T) MRI scanner, seven adults were stimulated with a figure-eight TMS coil over the left motor cortex for thumb, while continuously acquiring blood oxygen level dependent (BOLD) echoplanar images. TMS was applied at 1 Hz in 18-second long trains delivered alternately at 110% and 80% of motor threshold separated by rest periods. RESULTS: Though the TMS coil caused some artifacts and reduced the signal to noise ratio (SNR), higher intensity TMS caused greater activation than lower, both locally and remotely. The magnitude (approximately 3% increase) and temporal onset (2 to 5 sec) of TMS induced blood flow changes appear similar to those induced using other motor and cognitive tasks. CONCLUSIONS: Though work remains in refining this potentially powerful method, combined TMS/fMRI is both technically feasible and produces measurable dose-dependent changes in brain activity.

The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: a replication in healthy adults comparing two methods of assessing the distance to cortex.

Using transcranial magnetic stimulation (TMS), a handheld electrified copper coil against the scalp produces a powerful and rapidly oscillating magnetic field, which in turn induces electrical currents in the brain. The amount of electrical energy needed for TMS to induce motor movement (called the motor threshold [MT]), varies widely across individuals. The intensity of TMS is dosed relative to the MT. Kozel et al observed in a depressed cohort that MT increases as a function of distance from coil to cortex. This article examines this relationship in a healthy cohort and compares the two methods of assessing distance to cortex. Seventeen healthy adults had their TMS MT determined and marked with a fiducial. Magnetic resonance images showed the fiducials marking motor cortex, allowing researchers to measure distance from scalp to motor and prefontal cortex using two methods: 1) measuring a line from scalp to the nearest cortex and 2) sampling the distance from scalp to cortex of two 18-mm-square areas. Confirming Kozel's previous finding, we observe that motor threshold increases as distance to motor cortex increased for both methods of measuring distance and that no significant correlation exists between MT and prefontal cortex distance. Distance from TMS coil to motor cortex is an important determinant of MT in healthy and depressed adults. Distance to prefontal cortex is not correlated with MT, raising questions about the common practice of dosing prefontal stimulation using MT determined over motor cortex.

Unilateral left prefrontal transcranial magnetic stimulation (TMS) produces intensity-dependent bilateral effects as measured by interleaved BOLD fMRI.

Transcranial magnetic stimulation (TMS) administered over the prefrontal cortex has been shown to subtly influence neuropsychological tasks, and has antidepressant effects when applied daily for several weeks. Prefrontal TMS does not, however, produce an immediate easily observable effect, making it hard to determine if one has stimulated the cortex. Most prefrontal TMS studies have stimulated using intensity relative to the more easily determined motor threshold (MT) over motor cortex. Five healthy adults were studied in a 1.5 T MRI scanner during short trains of 1 Hz TMS delivered with a figure eight MR compatible TMS coil followed by rest epochs. In a randomized manner, left prefrontal TMS was delivered at 80%, 100% and 120% of MT interleaved with BOLD fMRI acquisition. Compared to rest, all TMS epochs activated auditory cortex, with 80% MT having no other areas of significant activation. 100% MT showed contralateral activation and 120% MT showed bilateral prefrontal activation. Higher intensity TMS, compared to lower, in general produced more activity both under the coil and contralaterally. Higher prefrontal TMS stimulation intensity produces greater local and contralateral activation. Importantly, unilateral prefrontal TMS produces bilateral effects, and TMS at 80% MT produces only minimal prefrontal cortex activation.

Vagus nerve stimulation therapy: a research update.

Over the past 5 years, and especially within the last year, there has been a rapid expansion of vagus nerve stimulation (VNS)-related preclinical research, as well as clinical studies in indications other than epilepsy. The research advances in understanding VNS are occurring in the midst of a blossoming of other forms of therapeutic brain stimulation, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). In general, improved understanding of the neurobiological effects of VNS therapy as a function of the different use parameters (frequency, intensity, pulse width, duration, dose) is beginning to guide clinical use and help determine which diseases, in addition to epilepsy, VNS might treat.

Safety and feasibility of repetitive transcranial magnetic stimulation in the treatment of anxious depression in pregnancy: a case report.

BACKGROUND: The proper treatment of mood disorders occurring during pregnancy is a major therapeutic problem since no antidepressant medications have been established as safe for the developing fetus. Several double-blind placebo-controlled studies have explored the efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression. CASE: We report the case of a 36-year-old woman in her second trimester of pregnancy, whose depression (DSM-IV) and anxiety were successfully treated with rTMS. Further studies of rTMS in depressed pregnant women appear warranted.

Feasibility of vagus nerve stimulation-synchronized blood oxygenation level-dependent functional MRI.

RATIONALE AND OBJECTIVES: Left cervical vagus nerve stimulation (VNS) by use of an implanted neurocybernetic prosthesis (NCP) system is effective in treating epilepsy, with open data suggesting effectiveness in depression, yet the mechanisms of action are unknown. Our objective was to develop a methodology for performing VNS-synchronized functional magnetic resonance imaging (VNS-fMRI) and then to demonstrate its feasibility for studying VNS effects. METHODS: In nine patients implanted for treatment of intractable depression, a Macintosh computer was used to detect the signal from the implanted VNS stimulator and then to synchronize fMRI image acquisition with its regular firing. RESULTS: With our VNS-fMRI methodology, the blood oxygenation level-dependent response to VNS was shown in brain regions regulated by the vagus nerve: orbitofrontal and parieto-occipital cortex bilaterally, left temporal cortex, the hypothalamus, and the left amygdala. CONCLUSIONS: Vagus nerve stimulation pulses from an NCP system can be detected externally to determine its firing pattern, thus allowing VNS-fMRI studies of VNS-induced brain activity.

Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement.

RATIONALE AND OBJECTIVES: The relatively high temporal and spatial resolution of functional MR imaging was used to compare the blood oxygenation level dependent (BOLD) response associated with movement induced by transcranial magnetic stimulation (TMS) with that for a similar movement executed volitionally (VOL). METHODS: Seven healthy adults were studied in a 1.5-T MR scanner. One hertz TMS at 110% of motor threshold was applied over the motor cortex for the thumb in 21-pulse trains in alternation with VOL every 63 seconds and interleaved with functional MR imaging. RESULTS: BOLD increases in motor cortex associated with TMS and VOL movement were similar (2%-3%). Mean separation of their centers of activity was 3.7 + 1.9 mm (mean displacement: left/right = 0.3 +/- 4.1 mm; superior/inferior = 0.7 +/- 1.9 mm). There was no indication of supraphysiological brain activity. CONCLUSIONS: Motor cortex BOLD response associated with thumb movement induced by 1-Hz TMS at 110% motor threshold is similar in both location and level to that caused by a similar movement executed volitionally.

Echoplanar BOLD fMRI of brain activation induced by concurrent transcranial magnetic stimulation.

RATIONALE AND OBJECTIVES: The authors demonstrate the feasibility of combining transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) inside an MR scanner to noninvasively stimulate and image regional brain activity. METHODS: Echoplanar blood oxygen level dependent (BOLD)-based fMRI studies of TMS response were performed on three human volunteers inside a standard 1.5 T MR scanner using independent computer control to interleave echoplanar image acquisition and stimulation of right thumb primary motor cortex with a nonferromagnetic TMS coil. RESULTS: Significant (P< 0.001) response was observed in motor cortex under the TMS coil during stimulation compared to rest, as well in auditory cortex, the latter presumably due to the loud "snap" when the coil was pulsed. CONCLUSIONS: Concurrent TMS stimulation and echoplanar BOLD fMRI imaging is possible. This method has potential for tracing neural circuits with brain imaging, as well as investigating the effects of TMS.

The relationship between alcohol consumption, health indicators and mortality in the German population.

BACKGROUND: The patterns of total alcohol, beer and wine consumption were evaluated in the German National Health Surveys. The impact of these habits on cardiovascular and all-cause mortality as well as cardiovascular risk factors and liver disease parameters was estimated. METHODS: Independent representative samples of the German population (15,400 people), and regional samples of the Berlin-Spandau population (2,370 in total), aged 25-69 years, were analysed. The amount and frequency of alcohol consumption was assessed with standardized questionnaires. Biochemical analyses included serum lipids and gamma-glutamyl-transpeptidase (Gamma GT). Multiple analyses of variance were used to determine the relationship between alcohol intake and biochemical parameters. A mortality follow-up of about 7 years was conducted for the Berlin-Spandau population. Proportional hazard models were used to estimate hazard ratios (HR) for all-cause and cardiovascular mortality. RESULTS: Over 80% of men and 55% of women in Germany drink alcohol on a regular base. The majority of the consumers (65% of men, 87% of women) are light (1-20 g/day) or moderate (21-40 g/day) drinkers. Higher serum high density lipoprotein (HDL)-cholesterol and Gamma GT levels were observed with increasing alcohol intake. In light and moderate drinkers no significant relationship was seen with non-HDL-cholesterol, triglycerides, blood pressure and body mass index, compared to teetotallers. Men who consumed 1-20 g alcohol/day had a significantly lower all-cause and cardiovascular mortality. As compared to nondrinkers, the risk was almost 50% lower. CONCLUSION: The results suggest that light (and possibly moderate) alcohol consumption reduces the risk of cardiovascular and total mortality risk and is favourably related to HDL-cholesterol.

Mapping transcranial magnetic stimulation (TMS) fields in vivo with MRI.

Transcranial magnetic stimulation (TMS) is a non-invasive technique for investigating brain function that uses pulsed magnetic fields created by special coils to induce localized neuronal depolarization. Despite the technique's expanding application, the exact magnetic field produced by TMS coils have never been directly measured in human subjects. Using a standard 1.5T MR scanner and TMS coils constructed from non magnetic materials, we have obtained 3D maps of the magnetic field created by TMS coils in human volunteers. Further, we mapped the combined field of two coils and demonstrated that combinations of coils might be used to focus the magnetic field to achieve improved stimulation patterns and, perhaps, reach areas out of reach of single coils.

Construction of an intrinsic cut-off value for the sero-epidemiological study of Trypanosoma evansi infections in a canine population in Brazil: a new approach towards an unbiased estimation of prevalence.

In the serodiagnosis of tropical infectious diseases, cut-off values are often established by using sera from individuals living under moderate climatic conditions, not exposed to the risk of infection (non-endemic controls). This approach guarantees the disease-free status of the individuals within that control group but leads to an assembly of samples which are not representative for the disease-free individuals of the target population (selection bias). Using data from an epidemiological study of Trypanosoma evansi infection in dogs, two alternative methods to construct cut-off values for a T. evansi antibody ELISA are described which are solely based on a distribution analysis of the data from the endemic animals. By cluster analysis these data could be divided into 'high', 'intermediate' and 'low responders'. High responders could also be identified by using the computer-assisted analysis of mixtures (C.A.MAN). Conventional cut-offs were calculated from a group of non-endemic individuals. A receiver operating characteristic (ROC) analysis was performed to demonstrate the impact of the choice of cut-offs on the test specificity and on the estimated seroprevalence among the endemic population. The data indicate that distribution analysis, especially the mixture analysis (C.A.MAN), are valuable tools for the unbiased estimation of seroprevalence when representative negative controls are not available.

How knowledge of regional brain dysfunction in depression will enable new somatic treatments in the next millennium.

New knowledge about the specific brain regions involved in depression is rapidly evolving due to advances in functional neuroimaging techniques. Several new regionally specific somatic interventions build on this modern neuroanatomic information. These latest methods promise to revolutionize the understanding and treatment of depression. This article reviews the past and current use of these techniques, with an eye toward where they are heading in the next century.

Vagus nerve stimulation: a new form of therapeutic brain stimulation.

Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.