Preliminary Technical Validation of LittleBeats™: A Multimodal Sensing Platform to Capture Cardiac Physiology, Motion, and Vocalizations.

Across five studies, we present the preliminary technical validation of an infant-wearable platform, LittleBeats™, that integrates electrocardiogram (ECG), inertial measurement unit (IMU), and audio sensors. Each sensor modality is validated against data from gold-standard equipment using established algorithms and laboratory tasks. Interbeat interval (IBI) data obtained from the LittleBeats™ ECG sensor indicate acceptable mean absolute percent error rates for both adults (Study 1, N = 16) and infants (Study 2, N = 5) across low- and high-challenge sessions and expected patterns of change in respiratory sinus arrythmia (RSA). For automated activity recognition (upright vs. walk vs. glide vs. squat) using accelerometer data from the LittleBeats™ IMU (Study 3, N = 12 adults), performance was good to excellent, with smartphone (industry standard) data outperforming LittleBeats™ by less than 4 percentage points. Speech emotion recognition (Study 4, N = 8 adults) applied to LittleBeats™ versus smartphone audio data indicated a comparable performance, with no significant difference in error rates. On an automatic speech recognition task (Study 5, N = 12 adults), the best performing algorithm yielded relatively low word error rates, although LittleBeats™ (4.16%) versus smartphone (2.73%) error rates were somewhat higher. Together, these validation studies indicate that LittleBeats™ sensors yield a data quality that is largely comparable to those obtained from gold-standard devices and established protocols used in prior research.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

Factores predictivos de conversión de colecistectomía laparoscópica. Artículo de Revisión / Predictive factors of laparoscopic cholecystectomy conversion. Review Article

Objetivo: establecer los factores predictivos y causas de conversión de la colecistectomía laparoscópica. Métodos: se trata de un metaanálisis en el que se realizó revisión bibliográfica a través de 8 bases de datos, se incluyeron 14 publicaciones correspondientes al periodo 2019 ­ 2023.Resultados : se encontró que los factores predictivos de conversión de colecistectomía laparoscópica se dividen en: factores propios del paciente: edad, género, índice de masa corporal, comórbidos, antecedente de cirugía abdominal; factores de la enfermedad: forma de ingreso del paciente bien sea electiva o de urgencia, presencia de colecistitis aguda, incremento del grosor de la pared vesicular, presencia de adherencias en el lecho operatorio; y factores del cirujano: que incluyen tanto la experiencia de este como la percepción de colecistectomía difícil.Conclusión : se ha logrado establecer en el presente trabajo que el sexo masculino, la edad avanzada, el mayor grosor de la pared de la vesícula biliar y la presencia de colecistitis aguda, representan factores predictivos de conversión de colecistectomía laparoscópica. Las principales causas de conversión fueron adherencias, dificultad de disección o visualización de las estructuras que componen el triángulo de Calot y hemorragia no controlada(AU)

Objective: to establish the predictive factors and causes of conversion of laparoscopic cholecystectomy. Methods: this is a qualitative research in which a bibliographic review was carried out through 8 databases, 14 publications corresponding to the period 2019 - 2023 were included.Results : it was found that the predictive factors of laparoscopic cholecystectomy conversion were They are divided into: factors specific to the patient: age, gender, body mass index, comorbidities, history of abdominal surgery; disease factors: admission of the patient, whether elective or urgent, presence of acute cholecystitis, increased thickness of the gallbladder wall, presence of adhesions in the surgical bed; and surgeon factors: which include both the surgeon's experience and the perception of difficult cholecystectomy.Conclusion : it has been established in the present work that the male sex, advanced age, greater thickness of the gallbladder wall and the presence of acute cholecystitis represent predictive factors for laparoscopic cholecystectomy conversion. The main causes of conversion were adhesions, difficulty in dissection or visualization of the structures that make up Calot's triangle, and uncontrolled bleeding(AU)

A pilot study on exertional tasks with physiological measures designed for the assessment of military concussion.

BACKGROUND: Guidelines for clinicians treating military concussion recommend exertional testing before return-to-duty, yet there is currently no standardized task or inclusion of an objective physiological measure like heart rate variability (HRV). METHODOLOGY & RESULTS: We pilot-tested two clinically feasible exertional tasks that include HRV measures and examined reliability of a commercially available heart rate monitor. Testing healthy participants confirmed that the 6-min step test and 2-min pushup test evoked the targeted physiological response, and the Polar H10 was reliable to the gold-standard electrocardiogram. CONCLUSION: Both tasks are brief assessments that can be implemented into primary care setting including the Polar H10 as an affordable way to access HRV. Additional research utilizing these tasks to evaluate concussion recovery can validate standardized exertional tasks for clinical use.

Posttraumatic Stress Disorder Subsequent to Apparent Mild Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) is prevalent among veterans with a history of traumatic brain injury (TBI); however, the relationship between TBI and PTSD is not well understood. We present the case of a 31-year-old male veteran with PTSD who reported TBI before entering the military. The reported injury appeared to be mild: He was struck on the head by a baseball, losing consciousness for ∼10 seconds. Years later, he developed severe PTSD after combat exposure. He was not receiving clinical services for these issues but was encountered in the context of a research study. We conducted cognitive, autonomic, and MRI assessments to assess brain function, structure, and neurophysiology. Next, we compared amygdala volume, uncinate fasciculus diffusion, functional connectivity, facial affect recognition, and baroreceptor coherence with those of a control group of combat veterans (n = 23). Our veteran's MRI revealed a large right medial-orbital prefrontal lesion with surrounding atrophy, which the study neuroradiologist interpreted as likely caused by traumatic injury. Comparison with controls indicated disrupted structural and functional connectivity of prefrontal-limbic structures and impaired emotional, cognitive, and autonomic responses. Detection of this injury before combat would have been unlikely in a clinical context because our veteran had reported a phenomenologically mild injury, and PTSD is a simple explanation for substance abuse, sleep impairment, and psychosocial distress. However, it may be that right prefrontal-limbic disruption imparted vulnerability for the development of PTSD and exacerbated our veteran's emotional response to, and recovery from, PTSD.

Use of Mobile Technology Paired with Heart Rate Monitor to Remotely Quantify Behavioral Health Markers among Military Reservists and First Responders.

INTRODUCTION: Heart rate variability (HRV) is a biological marker that reflects an individual's autonomic nervous system regulation. Psychological resilience is an individual's ability to recover from an adverse event and return to physiological homeostasis and mental well-being, indicated by higher resting HRV. The Biofeedback Assisted Resilience Training (BART) study evaluates a resilience-building intervention, with or without HRV biofeedback. This article evaluates the feasibility of remote psychophysiological research by validating the HRV data collected. MATERIALS AND METHODS: The BART platform consists of a mobile health application (BART app) paired to a wearable heart rate monitor. The BART app is installed on the participant's personal phone/tablet to track and collect self-report psychological and physiological data. The platform collects raw heart rate data and processes HRV to server as online biofeedback. The raw data is processed offline to derive HRV for statistical analysis. The following HRV parameters are validated: inter-beat interval, respiratory sinus arrhythmia, low-frequency HRV, biofeedback HRV, and heart period. Bland-Altman and scatter plots are used to compare and contrast online and offline HRV measures. Repeated-measures ANOVA are used to compared means across tasks during the stress (rest, stress, and recovery) and training (rest and paced breathing) sessions in order to validate autonomic nervous system changes to physiological challenges. RESULTS: The analyses included 245 participants. Bland-Altman plots showed excellent agreement and minimal bias between online and offline unedited inter-beat interval data during the stress session. RMANOVA during the training session indicated a significant strong effect on biofeedback HRV, F(11,390) = 967.96, P < .01. During the stress session, RMANOVA showed significant strong effect on respiratory sinus arrhythmia and low-frequency HRV, and a significant but weak effect on heart period. CONCLUSIONS: The BART digital health platform supports remote behavioral and physiological data collection, intervention delivery, and online HRV biofeedback.

Mental health, stress, and resilience correlates of heart rate variability among military reservists, guardsmen, and first responders.

The use of heart rate variability (HRV) for monitoring stress has been growing in the behavioral health literature, especially in the areas of posttraumatic stress disorder, stress reactivity, and resilience. Few studies, however, have included general populations under workplace conditions. This study evaluates whether military and other first responders show lower HRV during stress than at baseline and greater post stress rebound, controlling for a myriad of potential confounders. A convenience sample of Reserves, National Guard, veteran, fire, and police personnel provided HRV and self-reported questionnaire responses before, during, and after a cognitive-stressor task with a smart phone application. Timing of HRV application; mental and physical health scores; coping and posttraumatic growth indicators, including being open to new possibilities; and emotional support were predictors of trajectories of the HRV response to stress. Findings from this exploratory study emphasize the strong link between stress and relaxation breathing in both respiratory sinus arrhythmia and low frequency heart rate variability and the need for controlling potential covariates for understanding the relationship between HRV and the stress response and providing a basis for hypothesis driven research.

Targeting the Autonomic Nervous System Balance in Patients with Chronic Low Back Pain Using Transcranial Alternating Current Stimulation: A Randomized, Crossover, Double-Blind, Placebo-Controlled Pilot Study.

BACKGROUND: Chronic low back pain (CLBP) is characterized by an alteration in pain processing by the central nervous system that may affect autonomic nervous system (ANS) balance. Heart rate variability (HRV) reflects the balance of parasympathetic and sympathetic ANS activation. In particular, respiratory sinus arrhythmia (RSA) solely reflects parasympathetic input and is reduced in CLBP patients. Yet, it remains unknown if non-invasive brain stimulation can alter ANS balance in CLBP patients. OBJECTIVE: To evaluate if non-invasive brain stimulation modulates the ANS, we analyzed HRV metrics collected in a previously published study of transcranial alternating current stimulation (tACS) for the modulation of CLBP through enhancing alpha oscillations. We hypothesized that tACS would increase RSA. METHODS: A randomized, crossover, double-blind, sham-controlled pilot study was conducted to investigate the effects of 10Hz-tACS on metrics of ANS balance calculated from electrocardiogram (ECG). ECG data were collected for 2 mins before and after 40 mins of 10Hz-tACS or sham stimulation. RESULTS: There were no significant changes in RSA or other frequency-domain HRV components from 10Hz-tACS. However, exploratory time-domain HRV analyses revealed a significant increase in the standard deviation of normal intervals between R-peaks (SDNN), a measure of ANS balance, for 10Hz-tACS relative to sham. CONCLUSION: Although tACS did not significantly increase RSA, we found in an exploratory analysis that tACS modulated an integrated HRV measure of both ANS branches. These findings support the further study of how the ANS and alpha oscillations interact and are modulated by tACS. CLINICALTRIALSGOV: Transcranial Alternating Current Stimulation in Back Pain - Pilot Study, NCT03243084.

Biofeedback-Assisted Resilience Training for Traumatic and Operational Stress: Preliminary Analysis of a Self-Delivered Digital Health Methodology.

BACKGROUND: Psychological resilience is critical to minimize the health effects of traumatic events. Trauma may induce a chronic state of hyperarousal, resulting in problems such as anxiety, insomnia, or posttraumatic stress disorder. Mind-body practices, such as relaxation breathing and mindfulness meditation, help to reduce arousal and may reduce the likelihood of such psychological distress. To better understand resilience-building practices, we are conducting the Biofeedback-Assisted Resilience Training (BART) study to evaluate whether the practice of slow, paced breathing with or without heart rate variability biofeedback can be effectively learned via a smartphone app to enhance psychological resilience. OBJECTIVE: Our objective was to conduct a limited, interim review of user interactions and study data on use of the BART resilience training app and demonstrate analyses of real-time sensor-streaming data. METHODS: We developed the BART app to provide paced breathing resilience training, with or without heart rate variability biofeedback, via a self-managed 6-week protocol. The app receives streaming data from a Bluetooth-linked heart rate sensor and displays heart rate variability biofeedback to indicate movement between calmer and stressful states. To evaluate the app, a population of military personnel, veterans, and civilian first responders used the app for 6 weeks of resilience training. We analyzed app usage and heart rate variability measures during rest, cognitive stress, and paced breathing. Currently released for the BART research study, the BART app is being used to collect self-reported survey and heart rate sensor data for comparative evaluation of paced breathing relaxation training with and without heart rate variability biofeedback. RESULTS: To date, we have analyzed the results of 328 participants who began using the BART app for 6 weeks of stress relaxation training via a self-managed protocol. Of these, 207 (63.1%) followed the app-directed procedures and completed the training regimen. Our review of adherence to protocol and app-calculated heart rate variability measures indicated that the BART app acquired high-quality data for evaluating self-managed stress relaxation training programs. CONCLUSIONS: The BART app acquired high-quality data for studying changes in psychophysiological stress according to mind-body activity states, including conditions of rest, cognitive stress, and slow, paced breathing.

Autonomic regulation of preterm infants is enhanced by Family Nurture Intervention.

Preterm infants have maturational delays in several neurobehavioral systems. This study assesses the impact of the Family Nurture Intervention (FNI) in the neonatal intensive care unit (NICU) on the maturation of autonomic regulation of preterm infants. Preterm infants born at 26-34 weeks postmenstrual age (PMA) were assigned to groups receiving either standard care (SC) or SC plus FNI, using a randomized controlled trial design. At two collection time points, approximately 35 weeks and 41 weeks PMA, electrocardiograms (ECG) were monitored for approximately 1 hour during sleep. Heart rate and respiratory sinus arrhythmia (RSA) were quantified from the ECG. Across the two time points, the FNI group exhibited greater increases in RSA (Cohen's d = 0.35) and slope between RSA and heart rate, as a measure of vagal efficiency (Cohen's d = 0.62). These results document that FNI resulted in enhanced autonomic regulation consistent with greater maturation of cardiac function. These and previous findings strongly suggest that facilitating early nurturing interactions and emotional connection between preterm infants and their mothers is a practicable and effective means of optimizing postnatal development in preterm infants. Interpretation of these autonomic function results also enriches our understanding of the potential long-term beneficial outcomes of FNI by drawing upon polyvagal theory, which explains how autonomic state provides a neurophysiological platform for optimal co-regulation between infant and caregiver, and by drawing upon calming cycle theory, which provides a model for understanding how repeated mother/infant calming interactions positively condition autonomic state and reinforce approach, prosocial behaviors.

The PhysioCam: A Novel Non-Contact Sensor to Measure Heart Rate Variability in Clinical and Field Applications.

Heart rate variability (HRV) is a reliable indicator of health status and a sensitive index of autonomic stress reactivity. Stress negatively affects physical and psychological wellness by decreasing cardiovascular health and reducing quality of life. Wearable sensors have made it possible to track HRV during daily activity, and recent advances in mobile technology have reduced the cost and difficulty of applying this powerful technique. Although advances have made sensors smaller and lighter, some burden on the subject remains. Chest-worn electrocardiogram (ECG) sensors provide the optimal source signal for HRV analysis, but they require obtrusive electrode or conductive material adherence. A less invasive surrogate of HRV can be derived from the arterial pulse obtained using the photoplethysmogram (PPG), but sensor placement requirements limit the application of PPG in field research. Factors including gender, age, height, and weight also affect PPG-HRV level, but PPG-HRV is sufficient to track individual HRV reactions to physical and mental challenges. To overcome the limitations of contact sensors, we developed the PhysioCam (PhyC), a non-contact system capable of measuring arterial pulse with sufficient precision to derive HRV during different challenges. This passive sensor uses an off the shelf digital color video camera to extract arterial pulse from the light reflected from an individual's face. In this article, we validate this novel non-contact measure against criterion signals (ECG and PPG) in a controlled laboratory setting. Data from 12 subjects are presented under the following physiological conditions: rest, single deep breath and hold, and rapid breathing. The following HRV parameters were validated: interbeat interval (IBI), respiratory sinus arrhythmia (RSA), and low frequency HRV (LF). When testing the PhyC against ECG or PPG: the Bland-Altman plots for the IBIs show no systematic bias; correlation coefficients (all p values < 0.05) comparing ECG to PhyC for IBI and LF approach 1, while RSA correlations average 0.82 across conditions. We discuss future refinements of the HRV metrics derived from the PhyC that will enable this technology to unobtrusively track indicators of health and wellness.

Biobehavioral Insights into Adaptive Behavior in Complex and Dynamic Operational Settings: Lessons learned from the Soldier Performance and Effective, Adaptable Response Task.

The purpose of this study was to explore the biobehavioral correlates of adaptive behavior in the context of a standardized laboratory-based mission-relevant challenge [the Soldier Performance and Effective, Adaptable Response (SPEAR) task]. Participants were 26 healthy male volunteers (M = 34.85 years, SD = 4.12) with active military duty and leadership experience within the last 5 years (i.e., multiple leadership positions, operational deployments in combat, interactions with civilians and partner nation forces on the battlefield, experience making decisions under fire). The SPEAR task simultaneously engages perception, cognition, and action aspects of human performance demands similar to those encountered in the operational setting. Participants must engage with military-relevant text, visual, and auditory stimuli, interpret new information, and retain the commander's intent in working memory to create a new plan of action for mission success. Time-domain measures of heart period and respiratory sinus arrhythmia (RSA) were quantified, and saliva was sampled [later assayed for cortisol and alpha-amylase (sAA)] before-, during-, and post-SPEAR. Results revealed a predictable pattern of withdraw and recovery of the cardiac vagal tone during repeated presentation of battlefield challenges. Recovery of vagal inhibition following executive function challenge was strongly linked to better task-related performance. Rate of RSA recovery was also associated with better recall of the commander's intent. Decreasing magnitude in the skin conductance response prior to the task was positively associated with better overall task-related performance. Lower levels of RSA were observed in participants who reported higher rates of combat deployments, and reduced RSA flexibility was associated with higher rates of casualty exposure. Greater RSA flexibility during SPEAR was associated with greater self-reported resilience. There was no consistent pattern of task-related change in cortisol or sAA. We conclude that individual differences in psychophysiological reactivity and regulation in response to an ecologically valid, military-relevant task are associated with performance-related adaptive behavior in this standardized operational setting. The implications for modern day warfare, where advancing our understanding of the nature of individual differences in adaptive problem solving is critical to mission success, fitness for duty, and other occupational health-related outcomes, are discussed.

Optimizing Estimates of Instantaneous Heart Rate from Pulse Wave Signals with the Synchrosqueezing Transform.

BACKGROUND: With recent advances in sensor and computer technologies, the ability to monitor peripheral pulse activity is no longer limited to the laboratory and clinic. Now inexpensive sensors, which interface with smartphones or other computer-based devices, are expanding into the consumer market. When appropriate algorithms are applied, these new technologies enable ambulatory monitoring of dynamic physiological responses outside the clinic in a variety of applications including monitoring fatigue, health, workload, fitness, and rehabilitation. Several of these applications rely upon measures derived from peripheral pulse waves measured via contact or non-contact photoplethysmography (PPG). As technologies move from contact to non-contact PPG, there are new challenges. The technology necessary to estimate average heart rate over a few seconds from a noncontact PPG is available. However, a technology to precisely measure instantaneous heat rate (IHR) from non-contact sensors, on a beat-to-beat basis, is more challenging. OBJECTIVES: The objective of this paper is to develop an algorithm with the ability to accurately monitor IHR from peripheral pulse waves, which provides an opportunity to measure the neural regulation of the heart from the beat-to-beat heart rate pattern (i.e., heart rate variability). METHODS: The adaptive harmonic model is applied to model the contact or non-contact PPG signals, and a new methodology, the Synchrosqueezing Transform (SST), is applied to extract IHR. The body sway rhythm inherited in the non-contact PPG signal is modeled and handled by the notion of wave-shape function. RESULTS: The SST optimizes the extraction of IHR from the PPG signals and the technique functions well even during periods of poor signal to noise. We contrast the contact and non-contact indices of PPG derived heart rate with a criterion electrocardiogram (ECG). ECG and PPG signals were monitored in 21 healthy subjects performing tasks with different physical demands. The root mean square error of IHR estimated by SST is significantly better than commonly applied methods such as autoregressive (AR) method. In the walking situation, while AR method fails, SST still provides a reasonably good result. CONCLUSIONS: The SST processed PPG data provided an accurate estimate of the ECG derived IHR and consistently performed better than commonly applied methods such as autoregressive method.

Acoustic features of prairie vole (Microtus ochrogaster) ultrasonic vocalizations covary with heart rate.

Vocalizations serve as a conspecific social communication system among mammals. Modulation of acoustic features embedded within vocalizations is used by several mammalian species to signal whether it is safe or dangerous to approach conspecific and heterospecific mammals. As described by the Polyvagal Theory, the phylogenetic shift in the evolution of mammals involved an adaptive neuroanatomical link between the neural circuits regulating heart rate and the muscles involved in modulating the acoustic features of vocalizations. However, few studies have investigated the covariation between heart rate and the acoustic features of vocalizations. In the current study, we document that specific features of vocalizations covary with heart rate in a highly social and vocal mammal, the prairie vole (Microtus ochrogaster). Findings with the prairie vole illustrate that higher pitch (i.e., fundamental frequency) and less variability in acoustic features of vocalizations (i.e., less vocal prosody) are associated with elevated heart rate. The study provides the first documentation that the acoustic features of prairie vole vocalizations may function as a surrogate index of heart rate.

The covariation of acoustic features of infant cries and autonomic state.

The evolution of the autonomic nervous system provides an organizing principle to interpret the adaptive significance of physiological systems in promoting social behavior and responding to social challenges. This phylogenetic shift in neural regulation of the autonomic nervous system in mammals has produced a neuroanatomically integrated social engagement system, including neural mechanisms that regulate both cardiac vagal tone and muscles involved in vocalization. Mammalian vocalizations are part of a conspecific social communication system, with several mammalian species modulating acoustic features of vocalizations to signal affective state. Prosody, defined by variations in rhythm and pitch, is a feature of mammalian vocalizations that communicate emotion and affective state. While the covariation between physiological state and the acoustic frequencies of vocalizations is neurophysiologically based, few studies have investigated the covariation between vocal prosody and autonomic state. In response to this paucity of scientific evidence, the current study explored the utility of vocal prosody as a sensitive index of autonomic activity in human infants during the Still Face challenge. Overall, significant correlations were observed between several acoustic features of the infant vocalizations and autonomic state, demonstrating an association between shorter heart period and reductions in heart period and respiratory sinus arrhythmia following the challenge with the dampening of the modulation of acoustic features (fundamental frequency, variance, 50% bandwidth, and duration) that are perceived as prosody.

Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment.

Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels <0.1 mU/L. The effects of SHy on all-cause and cardiovascular mortality are not clear, but recent meta-analyses suggest a modest increase in mortality, with the risk increasing with age and associated with the lowest TSH levels. The long-term consequences of SHy in young- and middle-aged adults, and in those with TSH levels are mildly low, are uncertain. For these reasons, guidelines for treatment are based on patient age, the degree of TSH suppression, symptoms consistent with hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.