Prophylactic Oral Dextrose Gel and Neurosensory Impairment at 2-Year Follow-up of Participants in the hPOD Randomized Trial.

Importance: Prophylactic oral dextrose gel reduces neonatal hypoglycemia, but later benefits or harms remain unclear. Objective: To assess the effects on later development of prophylactic dextrose gel for infants born at risk of neonatal hypoglycemia. Design, Setting, and Participants: Prospective follow-up of a multicenter randomized clinical trial conducted in 18 Australian and New Zealand hospitals from January 2015 to May 2019. Participants were late preterm or term at-risk infants; those randomized in 9 New Zealand centers (n = 1359) were included and followed up between January 2017 and July 2021. Interventions: Infants were randomized to prophylactic 40% dextrose (n = 681) or placebo (n = 678) gel, 0.5 mL/kg, massaged into the buccal mucosa 1 hour after birth. Main Outcomes and Measures: The primary outcome of this follow-up study was neurosensory impairment at 2 years' corrected age. There were 44 secondary outcomes, including cognitive, language, and motor composite Bayley-III scores (mean [SD], 100 [15]; higher scores indicate better performance). Results: Of eligible infants, 1197 (91%) were assessed (581 females [49%]). Neurosensory impairment was not significantly different between the dextrose and placebo gel groups (20.8% vs 18.7%; unadjusted risk difference [RD], 2.09% [95% CI, -2.43% to 6.60%]; adjusted risk ratio [aRR], 1.13 [95% CI, 0.90 to 1.41]). The risk of cognitive and language delay was not significantly different between the dextrose and placebo groups (cognitive: 7.6% vs 5.3%; RD, 2.32% [95% CI, -0.46% to 5.11%]; aRR, 1.40 [95% CI, 0.91 to 2.17]; language: 17.0% vs 14.7%; RD, 2.35% [95% CI, -1.80% to 6.50%]; aRR, 1.19 [95% CI, 0.92 to 1.54]). However, the dextrose gel group had a significantly higher risk of motor delay (2.5% vs 0.7%; RD, 1.81% [95% CI, 0.40% to 3.23%]; aRR, 3.79 [95% CI, 1.27 to 11.32]) and significantly lower composite scores for cognitive (adjusted mean difference [aMD], -1.30 [95% CI, -2.55 to -0.05]), language (aMD, -2.16 [95% CI, -3.86 to -0.46]), and motor (aMD, -1.40 [95% CI, -2.60 to -0.20]) performance. There were no significant differences between groups in the other 27 secondary outcomes. Conclusions and Relevance: Among late preterm and term infants born at risk of neonatal hypoglycemia, prophylactic oral 40% dextrose gel at 1 hour of age, compared with placebo, resulted in no significant difference in the risk of neurosensory impairment at 2 years' corrected age. However, the study may have been underpowered to detect a small but potentially clinically important increase in risk, and further research including longer-term follow-up is required. Trial Registration: anzctr.org.au Identifier: ACTRN12614001263684.

Physical impairments, sensory disturbance, and functional ability in a cancer patient with and without chemotherapy-induced peripheral neuropathy symptoms.

OBJECTIVE: The present study examined the objective and patient-reported measures of physical impairments, sensory disturbance, and functional ability between cancer patients with and without chemotherapy-induced peripheral neuropathy (CIPN) symptoms. METHODS: Forty-one cancer survivors exposed to neurotoxic chemotherapies were conveniently recruited and completed a single cross-sectional assessment of patient-reported outcomes (VAS for pain intensity and ABC scale) and objective assessments (SWM test, TUG test, 5xSTS test, Romberg test with eyes open and eyes closed, 6MWT, and FAB scale). RESULTS: Cancer patients who had undergone chemotherapy with CIPN symptoms did significantly worse in the SWM test, TUG test, 5xSTS test, Romberg test with eyes closed, 6MWT, FAB scale, and ABC scale (p < 0.05) when compared with cancer survivors without CIPN symptoms. CONCLUSION: Cancer survivors with CIPN symptoms have lower physical performance, sensory perception, and functional ability, which may increase the risk of falling and disability. These findings further emphasize the need for effective rehabilitation and interventions to treat CIPN symptoms and related physical impairment and functional deficits.

Effects of Caffeine Ingestion on Human Standing Balance: A Systematic Review of Placebo-Controlled Trials.

Caffeine ingestion may influence balance control via numerous mechanisms. Although previously investigated using various study designs and methods, here we aimed to create the first evidence-based consensus regarding the effects of caffeine on the control of upright stance via systematic review (PROSPERO registration CRD42021226939). Embase, PubMed/MEDLINE, SPORTDiscus and Web of Science databases were searched on 27 January 2021 to identify placebo-controlled trials investigating caffeine-induced changes in human standing balance. Reference lists of eligible studies were also searched. Overall, nine studies involving a total of 290 participants were included. All studies were moderate to strong in quality according to the QualSyst tool. Balance-related outcome measures were collected across a range of different participant ages, stances and sensory conditions. The results show that younger participants' balance was generally unaffected by caffeine ingestion. However, a significant balance impairment was observed following caffeine ingestion in all studies involving older participants (average age >65 years). Our results therefore suggest an age-dependent effect of caffeine ingestion on human standing. Further research into this effect is warranted as only one study has directly compared younger and older adults. Nonetheless, an important implication of our findings is that caffeine ingestion may increase fall risk in older adults. Furthermore, based on our findings, caffeine ingestion should be considered as a potential confounding factor when assessing human standing balance, particularly in older adults.

Downregulation of microRNA-199a-5p alleviated lidocaine-induced sensory dysfunction and spinal cord myelin lesions in a rat model.

Lidocaine induces neurotoxicity in the spinal cord, but the underlying mechanisms remain unclear. In this study, we evaluated the effects of miR-199a-5p on 10 % lidocaine neurotoxicity. Increased expression of miR-199a-5p in the spinal cord of rats treated with 10 % lidocaine was assessed by qRT-PCR. Furthermore, after miR-199a-5p antagomir administration, the sensory dysfunction and myelin sheath lesions (evaluated by semithin sections stained with toluidine blue, electron microscopy, g-ratios and myelin thickness) induced by 10 % lidocaine were alleviated. Myelin regulatory factor (MYRF), a key molecule of myelin sheath development, was predicted to be a target gene of miR-199a-5p by the TargetScan and miRBase databases. MYRF and its downstream factors myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) were significantly decreased after intrathecal 10 % lidocaine administration. Moreover, these changes were reversed after miR-199a-5p antagomir administration. FISH-immunofluorescence showed coexpression of miR-199a-5p and MYRF in the spinal cord white matter of rats. A luciferase reporter assay further demonstrated the functional association between miR-199a-5p and MYRF. Overall, miR-199a-5p upregulation is involved in 10 % lidocaine-induced spinal cord toxicity through regulation of MYRF. Therefore, downregulating miR-199a-5p expression may be a potential strategy to ameliorate spinal cord neurotoxicity induced by 10 % lidocaine.

In utero exposure to protease inhibitor-based antiretroviral regimens delays growth and developmental milestones in mice.

Antiretroviral therapy (ART) in pregnancy has dramatically reduced HIV vertical transmission rates. Consequently, there is a growing number of children that are HIV exposed uninfected (CHEUs). Studies suggest that CHEUs exposed in utero to ART may experience developmental delays compared to their peers. We investigated the effects of in utero ART exposure on perinatal neurodevelopment in mice, through assessment of developmental milestones. Developmental milestone tests (parallel to reflex testing in human infants) are reflective of brain maturity and useful in predicting later behavioral outcomes. We hypothesized that ART in pregnancy alters the in utero environment and thereby alters developmental milestone outcomes in pups. Throughout pregnancy, dams were treated with boosted-atazanavir combined with either abacavir/lamivudine (ATV/r/ABC/3TC), or tenofovir/emtricitabine (ATV/r/TDF/FTC), or water as control. Pups were assessed daily for general somatic growth and on a battery of tests for primitive reflexes including surface-righting, negative-geotaxis, cliff-aversion, rooting, ear-twitch, auditory-reflex, forelimb-grasp, air-righting, behaviors in the neonatal open field, and olfactory test. In utero exposure to either ART regimen delayed somatic growth in offspring and evoked significant delays in the development of negative geotaxis, cliff-aversion, and ear-twitch reflexes. Exposure to ATV/r/ABC/3TC was also associated with olfactory deficits in male and forelimb grasp deficits in female pups. To explore whether delays persisted into adulthood we assessed performance in the open field test. We observed no significant differences between treatment arm for males. In females, ATV/r/TDF/FTC exposure was associated with lower total distance travelled and less ambulatory time in the centre, while ATV/r/ABC/3TC exposure was associated with higher resting times compared to controls. In utero PI-based ART exposure delays the appearance of primitive reflexes that involve vestibular and sensory-motor pathways in a mouse model. Our findings suggest that ART could be disrupting the normal progress/maturation of the underlying neurocircuits and encourage further investigation for underlying mechanisms.

The synthetic cannabinoid 5F-MDMB-PICA: A case series.

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1-16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected. In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected. The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech. Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases.

Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment.

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research. Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis. Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes. Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary. Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance. Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) µg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) µg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed. Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

A new approach to characterize postural deficits in chemotherapy-induced peripheral neuropathy and to analyze postural adaptions after an exercise intervention.

BACKGROUND: Postural instability presents a common and disabling consequence of chemotherapy-induced peripheral neuropathy (CIPN). However, knowledge about postural behavior of CIPN patients is sparse. With this pilot study, we used a new approach to i) characterize postural impairments as compared to healthy subjects, ii) allocate possible abnormalities to a set of parameters describing sensorimotor function, and iii) evaluate the effects of a balance-based exercise intervention. METHODS: We analyzed spontaneous and externally perturbed postural control in eight CIPN patients before and after a balance-based exercise intervention by using a modification of an established postural control model. These findings were compared to 15 matched healthy subjects. RESULTS: Spontaneous sway amplitude and velocity were larger in CIPN patients compared to healthy subjects. CIPN patients' reactions to external perturbations were smaller compared to healthy subjects, indicating that patients favor vestibular over proprioceptive sensory information. The balance-based exercise intervention up-weighted proprioceptive information in patients. CONCLUSIONS: CIPN patients' major postural deficit may relate to underuse of proprioceptive information that results in a less accurate posture control as spontaneous sway results indicate. The balance-based exercise intervention is able to partially correct for this abnormality. Our study contributes to a better understanding of postural impairments in CIPN patients and suggests an effective treatment strategy. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004340, retrospectively registered 04 January 2013.

[Influence of diagnostic pathway on clinical and non-conventional therapies use in women with breast cancer of the cohort DAMA]. / Influencia de la vía diagnóstica en la clínica y el uso de terapias no convencionales en mujeres con cáncer de mama de la cohorte DAMA.

OBJECTIVE: To describe and analyze the characteristics of breast cancer tumours according to the diagnostic pathway. We analyse the adverse effects of the treatments and the use of unconventional therapies in order to alleviate them. METHOD: Descriptive design nested in a mixed cohort (Cohort DAMA). The dependent variable was the route to diagnosis of breast cancer. The independent variables were age, body mass index, social class, disposable family income, type of tumour, histological degree, tumour stage, recurrences, treatment, adverse effects derived from treatments and unconventional therapies. Bivariate descriptive analyses were performed and univariate and multivariate regression models were adjusted; and graphic representations of the unconventional therapies. RESULTS: There are differences in the characteristics of the tumours, and the impact of the adverse effects derived from the treatments. The patients diagnosed by screening were older, from a high social class, had a higher percentage of tumours of grade I differentiation, initial stages, fewer recurrences and fewer adverse effects due to treatment, although this was not different in the screening group compared to the rest. There was also less use of unconventional therapies. CONCLUSIONS: The results indicate that the implementation of screening programmes increases the possibility of detecting tumours in initial stages and with therapies with fewer adverse effects. As a result, there is less need to resort to unconventional therapies.

Freezing of gait and postural instability: the unpredictable response to levodopa in Parkinson's disease.

Freezing of gait (FOG) and postural instability are challenging motor symptoms that present a serious therapeutic dilemma in Parkinson's disease. Appropriate distinction between FOG subtypes may be difficult during routine clinical visits, as shown in the case we present. The patient was examined in three different states in relation to levodopa (L-DOPA) and apomorphine subcutaneous (sc) tests with video documentation: (1) 'overnight-off', after 12 hours without medication; (2)'on', 60 min after intake of regular levodopa dose (200 mg) and 20 min after 2 mg of apomorphine sc; and (3) 'supra-on', after 350 mg of L-DOPA and 3 mg of apomorphine sc. The patient clearly showed a dose-dependent paradoxical response to L-DOPA treatment with the emergence of severe FOG and postural instability. The tendency to develop these axial symptoms was less pronounced with apomorphine at doses that achieved similar improvements of other Parkinsonian features.

Childhood leukemia survivors exhibit deficiencies in sensory and cognitive processes, as reflected by event-related brain potentials after completion of curative chemotherapy: A preliminary investigation.

Objective: The purpose of this study was to characterize post-chemotherapy sensory, memory, and attention abilities in childhood survivors of acute lymphoblastic leukemia (ALL) to better understand how treatment affects cognitive functioning. Methods: Eight ALL survivors and eight age-matched, healthy children between the ages of 5-11 years participated in the study. Among the ALL survivors, a median of 63 days (range 22-267 days) elapsed between completion of chemotherapy and this assessment. Sounds were presented in an oddball paradigm while recording the electroencephalogram in separate conditions of passive listening and active task performance. To assess different domains of cognition, we measured event-related brain potentials (ERPs) reflecting sensory processing (P1 component), working memory (mismatch negativity [MMN] component), attentional orienting (P3a), and target detection (P3b component) in response to the sounds. We also measured sound discrimination and response speed performance. Results: Relative to control subjects, ALL survivors had poorer performance on auditory tasks, as well as decreased amplitude of the P1, MMN, P3a, and P3b components. ALL survivors also did not exhibit the amplitude gain typically observed in the sensory P1 component when attending to the sound input compared to when passively listening. Conclusions: Atypical responses were observed in brain processes associated with sensory discrimination, auditory working memory, and attentional control in pediatric ALL survivors indicating deficiencies in all cognitive domains compared to age-matched controls. Significance: ERPs differentiated aspects of cognitive functioning, which may provide a useful tool for assessing recovery and risk of post-chemotherapy cognitive deficiencies in young children. The decreased MMN amplitude in ALL survivors may indicate (N-methyl D-aspartate) NMDA dysfunction induced by methotrexate, and thus provides a potential therapeutic target for chemotherapy-associated cognitive impairments.

cVEMP correlated with imbalance in a mouse model of vestibular disorder.

BACKGROUND: Cervical vestibular evoked myogenic potential (cVEMP) testing is a strong tool that enables objective determination of balance functions in humans. However, it remains unknown whether cVEMP correctly expresses vestibular disorder in mice. OBJECTIVE: In this study, correlations of cVEMP with scores for balance-related behavior tests including rotarod, beam, and air-righting reflex tests were determined in ICR mice with vestibular disorder induced by 3,3'-iminodipropiontrile (IDPN) as a mouse model of vestibular disorder. METHODS: Male ICR mice at 4 weeks of age were orally administered IDPN in saline (28 mmol/kg body weight) once. Rotarod, beam crossing, and air-righting reflex tests were performed before and 3-4 days after oral exposure one time to IDPN to determine balance functions. The saccule and utricles were labeled with fluorescein phalloidin. cVEMP measurements were performed for mice in the control and IDPN groups. Finally, the correlations between the scores of behavior tests and the amplitude or latency of cVEMP were determined with Spearman's rank correlation coefficient. Two-tailed Student's t test and Welch's t test were used to determine a significant difference between the two groups. A difference with p < 0.05 was considered to indicate statistical significance. RESULTS: After oral administration of IDPN at 28 mmol/kg, scores of the rotarod, beam, and air-righting reflex tests in the IDPN group were significantly lower than those in the control group. The numbers of hair cells in the saccule, utricle, and cupula were decreased in the IDPN group. cVEMP in the IDPN group was significantly decreased in amplitude and increased in latency compared to those in the control group. cVEMP amplitude had significant correlations with the numbers of hair cells as well as scores for all of the behavior tests in mice. CONCLUSIONS: This study demonstrated impaired cVEMP and correlations of cVEMP with imbalance determined by behavior tests in a mouse model of vestibular disorder.

Peripheral neuropathy induced by drinking water contaminated with low-dose arsenic in Myanmar.

BACKGROUND: More than 140 million people drink arsenic-contaminated groundwater. It is unknown how much arsenic exposure is necessary to cause neurological impairment. Here, we evaluate the relationship between neurological impairments and the arsenic concentration in drinking water (ACDW). PARTICIPANTS AND METHODS: A cross-sectional study design was employed. We performed medical examinations of 1867 residents in seven villages in the Thabaung township in Myanmar. Medical examinations consisted of interviews regarding subjective neurological symptoms and objective neurological examinations of sensory disturbances. For subjective neurological symptoms, we ascertained the presence or absence of defects in smell, vision, taste, and hearing; the feeling of weakness; and chronic numbness or pain. For objective sensory disturbances, we examined defects in pain sensation, vibration sensation, and two-point discrimination. We analyzed the relationship between the subjective symptoms, objective sensory disturbances, and ACDW. RESULTS: Residents with ACDW ≥ 10 parts per billion (ppb) had experienced a "feeling of weakness" and "chronic numbness or pain" significantly more often than those with ACDW < 10 ppb. Residents with ACDW ≥ 50 ppb had three types of sensory disturbances significantly more often than those with ACDW < 50 ppb. In children, there was no significant association between symptoms or signs and ACDW. CONCLUSION: Subjective symptoms, probably due to peripheral neuropathy, occurred at very low ACDW (around 10 ppb). Objective peripheral nerve disturbances of both small and large fibers occurred at low ACDW (> 50 ppb). These data suggest a threshold for the occurrence of peripheral neuropathy due to arsenic exposure, and indicate that the arsenic concentration in drinking water should be less than 10 ppb to ensure human health.

A multidimensional concept for mercury neuronal and sensory toxicity in fish - From toxicokinetics and biochemistry to morphometry and behavior.

BACKGROUND: Neuronal and sensory toxicity of mercury (Hg) compounds has been largely investigated in humans/mammals with a focus on public health, while research in fish is less prolific and dispersed by different species. Well-established premises for mammals have been governing fish research, but some contradictory findings suggest that knowledge translation between these animal groups needs prudence [e.g. the relative higher neurotoxicity of methylmercury (MeHg) vs. inorganic Hg (iHg)]. Biochemical/physiological differences between the groups (e.g. higher brain regeneration in fish) may determine distinct patterns. This review undertakes the challenge of identifying sensitive cellular targets, Hg-driven biochemical/physiological vulnerabilities in fish, while discriminating specificities for Hg forms. SCOPE OF REVIEW: A functional neuroanatomical perspective was conceived, comprising: (i) Hg occurrence in the aquatic environment; (ii) toxicokinetics on central nervous system (CNS)/sensory organs; (iii) effects on neurotransmission; (iv) biochemical/physiological effects on CNS/sensory organs; (v) morpho-structural changes on CNS/sensory organs; (vi) behavioral effects. The literature was also analyzed to generate a multidimensional conceptualization translated into a Rubik's Cube where key factors/processes were proposed. MAJOR CONCLUSIONS: Hg neurosensory toxicity was unequivocally demonstrated. Some correspondence with toxicity mechanisms described for mammals (mainly at biochemical level) was identified. Although the research has been dispersed by numerous fish species, 29 key factors/processes were pinpointed. GENERAL SIGNIFICANCE: Future trends were identified and translated into 25 factors/processes to be addressed. Unveiling the neurosensory toxicity of Hg in fish has a major motivation of protecting ichtyopopulations and ecosystems, but can also provide fundamental knowledge to the field of human neurodevelopment.

Cognitive and neurobehavioral benefits of an enriched environment on young adult mice after chronic ethanol consumption during adolescence.

Binge drinking (BD) is a common pattern of ethanol (EtOH) consumption by adolescents. The brain effects of the acute EtOH exposure are well-studied; however, the long-lasting cognitive and neurobehavioral consequences of BD during adolescence are only beginning to be elucidated. Environmental enrichment (EE) has long been known for its benefits on the brain and may serve as a potential supportive therapy following EtOH exposure. In this study, we hypothesized that EE may have potential benefits on the cognitive deficits associated with BD EtOH consumption. Four-week-old C57BL/6J male mice were exposed to EtOH following an intermittent 4-day drinking-in-the-dark procedure for 4 weeks. Then they were exposed to EE during EtOH withdrawal for 2 weeks followed by a behavioral battery of tests including novel object recognition, novel location, object-in-place, rotarod, beam walking balance, tail suspension, light-dark box and open field that were run during early adulthood. Young adult mice exposed to EE significantly recovered recognition, spatial and associative memory as well as motor coordination skills and balance that were significantly impaired after adolescent EtOH drinking with respect to controls. No significant permanent anxiety or depressive-like behaviors were observed. Taken together, an EE exerts positive effects on the long-term negative cognitive deficits as a result of EtOH consumption during adolescence.

Association Between Psychotropic Medication Polypharmacy and an Objective Measure of Balance Impairment Among Middle-Aged Adults: Results from the US National Health and Nutrition Examination Survey.

OBJECTIVE: Psychotropic medications (e.g., antidepressants, anxiolytics, and neuroleptics) are increasingly prescribed with two or more taken concurrently (polypharmacy), and have been associated with an increased risk of falling. The aim of this study was to examine the association between psychotropic medication use and balance impairment using an objective balance measure. METHODS: We derived data from participants aged 40 years and older in the US National Health and Nutrition Examination Survey (1999/00-2003/04) who completed the Modified Clinical Trial of Sensory Interaction and Balance and indicated current medications (n = 3090). Balance impairment was defined as failing the Modified Clinical Trial of Sensory Interaction and Balance condition 4 (standing on foam surface, eyes closed). Medication use included specific psychotropic classes, a count of psychotropic medications, and a count of non-psychotropic medications taken concurrently. Nested multiple logistic regression assessed relationships between medication use and balance impairment, adjusting for covariates and complex sampling. RESULTS: One third of participants had balance impairment. After accounting for medical comorbidities, there was no relationship between individual classes of psychotropic medications and balance impairment. After adjusting for all covariates, there was a dose-response relationship between the number of psychotropic medications taken and balance impairment, with every additional medication associated with a 35% higher odds (odds ratio = 1.35; 95% confidence interval 1.07-1.70). In comparison, there was no increase in the odds of balance impairment associated with each additional medication taken for participants only taking non-psychotropic medications. CONCLUSIONS: Psychotropic medication polypharmacy is associated with an increased odds of balance impairment. Clinicians should exercise caution when prescribing combinations of psychotropic medications, and refer to physical therapy for assessment and treatment if balance impairment is detected.

Development and preliminary testing of a brief clinical tool to enable daily monitoring of chemotherapy toxicity: The Daily Chemotherapy Toxicity self-Assessment Questionnaire.

Close monitoring of chemotherapy toxicity can be instrumental in ensuring prompt symptom management and quality care. Our aim was to develop a brief clinical tool to enable daily assessment of chemotherapy toxicity and investigate/establish its content validity, feasibility/applicability, internal consistency and stability. Development of the Daily Chemotherapy Toxicity self-Assessment Questionnaire (DCTAQ) was based on an initial item pool created from two scoping reviews. Expert panel review (n = 15) and cognitive debriefing with patients with cancer (n = 7) were used to establish content validity. Feasibility/acceptability, applicability (self-report vs. interview-like administration), internal consistency (KR-20) and test-retest reliability (at 1-hr intervals) of the DCTAQ were field-tested with 82 patients with breast or colorectal cancer receiving active chemotherapy at eight hospitals. Initial development/content validity stages enabled item revisions and re-wording that led to a final, 11-item DCTAQ version with 10 core symptom items plus one open-ended "any other symptom" item. Feasibility and acceptability were demonstrated through the absence of participant withdrawals, absence of missing data and no complaints about tool length. The DCTAQ was found to have modest internal consistency (KR-20 = 0.56), but very good test-retest reliability. The DCTAQ is a brief clinical tool that allows for rapid and accurate daily assessments of chemotherapy toxicity in clinical practice.

Subanaesthetic ketamine and altered states of consciousness in humans.

BACKGROUND: Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. METHODS: High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg-1 over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes. RESULTS: Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8-12 Hz) in parietal (-0.94 dB, P<0.001) and occipital (-1.8 dB, P<0.001) channel clusters. Significant decreases in alpha were identified in the precuneus and temporal-parietal junction. CONCLUSIONS: Ketamine induces altered states of consciousness during periods of reduced alpha power in the precuneus and temporal-parietal junction. Modulation of these temporal-parietal loci are candidate mechanisms of the psychoactive effects of ketamine, given that this region is involved in multisensory integration, body representation, and consciousness.

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

Importance: In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. Objective: To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. Design, Setting, and Participants: In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Exposures: Chemotherapy agents known to be toxic to peripheral nerves. Main Outcomes and Measures: The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Results: Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 µV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids. Conclusions and Relevance: Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.

Sufentanil Alleviates Intrathecal Lidocaine Induced Prolonged Sensory and Motor Impairments but not the Spinal Histological Injury in Rats.

Spinal anesthesia has evolved into a safe and widely accepted method of anesthesia. Synergy between opioids and local anesthetics further increases the quality of analgesia and decreases the dose requirement of both local anesthetics and opioids. However, over the last decades compelling evidence suggested that lidocaine could be more neurotoxic than other commonly used local anesthetics. Whether opioids can modify the local anesthetics-induced neurotoxicity is largely unexplored. Here, we investigated the effect of sufentanil on the neurotoxicity induced by intrathecal lidocaine in a rat model. Our data showed that 5 µg/ml sufentanil didn't deteriorate nor reduce the histopathological injuries induced by intrathecal application of 10% lidocaine in a rat model. However, it did alleviate sensory and motor function impairments induced by 10% lidocaine. Repeated intrathecal injection of 5 µg/ml sufentanil also decreased the paw withdraw threshold compared to the baseline. An increase in expression of activating transcription factor 3, a stress response gene, as a marker for injured neurons, was also detected in lidocaine-induced neurotoxicity, while 5 µg/ml sufentanil inhibited lidocaine-induced the upregulation of activating transcription factor 3. These results suggest that sufentanil alleviates lidocaine induced sensory and motor impairments, and did not worsen histopathological injury induced by intrathecal lidocaine.