Variation in care and outcome for fragile hip fracture patients: a European multicentre study benchmarking fulfilment of established quality indicators.

PURPOSE: Despite the availability of clinical guidelines for hip fracture patients, adherence to these guidelines is challenging, potentially resulting in suboptimal patient care. The goal of this study was (1) to evaluate and benchmark the adherence to recently established quality indicators (QIs), and (2) to study clinical outcomes, in fragile hip fracture patients from different European countries. METHODS: This observational, cross-sectional multicenter study was performed in 10 hospitals from 9 European countries including data of 298 consecutive patients. RESULTS: A large variation both within and between hospitals were seen regarding adherence to the individual QIs. QIs with the lowest overall adherence rates were the administration of systemic steroids (5.4%) and tranexamic acid (20.1%). Indicators with the highest adherence rates (above 95%) were pre-operative (99.3%) and post-operative haemoglobin level assessment (100%). The overall median time to surgery was 22.6 h (range 15.7-42.5 h). The median LOS was 9.0 days (range 5.0-19.0 days). The most common complications were delirium (23.2%) and postsurgical constipation (25.2%). CONCLUSION: The present study shows large variation in the care for fragile patients with hip fractures indicating room for improvement. Therefore, hospitals should invest in benchmarking and knowledge-sharing. Large quality improvement initiatives with longitudinal follow up of both process and outcome indicators should be initiated.

The role of depression in the association between mobilisation timing and live discharge after hip fracture surgery: Secondary analysis of the UK National Hip Fracture Database.

PURPOSE: The aim was to compare the probability of discharge after hip fracture surgery conditional on being alive and in hospital between patients mobilised within and beyond 36-hours of surgery across groups defined by depression. METHODS: Data were taken from the National Hip Fracture Database and included patients 60 years of age or older who underwent hip fracture surgery in England and Wales between 2014 and 2016. The conditional probability of postsurgical live discharge was estimated for patients mobilised early and for patients mobilised late across groups with and without depression. The association between mobilisation timing and the conditional probability of live discharge were also estimated separately through adjusted generalized linear models. RESULTS: Data were analysed for 116,274 patients. A diagnosis of depression was present in 8.31% patients. In those with depression, 7,412 (76.7%) patients mobilised early. In those without depression, 84,085 (78.9%) patients mobilised early. By day 30 after surgery, the adjusted odds ratio of discharge among those who mobilised early compared to late was 1.79 (95% CI: 1.56-2.05, p<0.001) and 1.92 (95% CI: 1.84-2.00, p<0.001) for those with and without depression, respectively. CONCLUSION: A similar proportion of patients with depression mobilised early after hip fracture surgery when compared to those without a diagnosis of depression. The association between mobilisation timing and time to live discharge was observed for patients with and without depression.

Determinants of Microscale pH in In Situ-Grown Dental Biofilms.

Dental biofilm pH is the most important determinant of virulence for the development of caries lesions. Confocal microscopy-based pH ratiometry allows monitoring biofilm pH with high spatial resolution. Experiments performed on simplified biofilm models under static conditions identified steep pH gradients as well as localized acidogenic foci that promote enamel demineralization. The present work used pH ratiometry to perform a comprehensive analysis of the effect of whole saliva flow on the microscale pH in complex, in situ-grown 48-h and 96-h biofilms (n = 54) from 9 healthy participants. pH was monitored in 12 areas at the biofilm bottom and top, and saliva flow with film thicknesses corresponding to those in the oral cavity was provided by an additively manufactured microfluidic flow cell. Biofilm pH was correlated to the bacterial composition, as determined by 16S rRNA gene sequencing. Biofilm acidogenicity varied considerably between participants and individual biofilms but also between different areas inside one biofilm, with pH gradients of up to 2 units. pH drops were more pronounced in 96-h than in 48-h biofilms (P = 0.0121) and virtually unaffected by unstimulated saliva flow (0.8 mm/min). Stimulated flow (8 mm/min) raised average biofilm pH to near-neutral values but it did not equilibrate vertical and horizontal pH gradients in the biofilms. pH was significantly lower at the biofilm base than at the top (P < 0.0001) and lower downstream than upstream (P = 0.0046), due to an accumulation of acids along the flow path. pH drops were positively correlated with biofilm thickness and negatively with the thickness of the saliva film covering the biofilm. Bacterial community composition was significantly different between biofilms with strong and weak pH responses but not their species richness. The present experimental study demonstrates that stimulated saliva flow, saliva film thickness, biofilm age, biofilm thickness, and bacterial composition are important modulators of microscale pH in dental biofilms.

The impact of the frequency, duration and type of physiotherapy on discharge after hip fracture surgery: a secondary analysis of UK national linked audit data.

Additional physiotherapy in the first postoperative week was associated with fewer days to discharge after hip fracture surgery. A 7-day physiotherapy service in the first postoperative week should be considered as a new key performance indicator in evaluating the quality of care for patients admitted with a hip fracture. INTRODUCTION: To examine the association between physiotherapy in the first week after hip fracture surgery and discharge from acute hospital. METHODS: We linked data from the UK Physiotherapy Hip Fracture Sprint Audit to hospital records for 5395 patients with hip fracture in May and June 2017. We estimated the association between the number of days patients received physiotherapy in the first postoperative week; its overall duration (< 2 h, ≥ 2 h; 30-min increment) and type (mobilisation alone, mobilisation and exercise) and the cumulative probability of discharge from acute hospital over 30 days, using proportional odds regression adjusted for confounders and the competing risk of death. RESULTS: The crude and adjusted odds ratios of discharge were 1.24 (95% CI 1.19-1.30) and 1.26 (95% CI 1.19-1.33) for an additional day of physiotherapy, 1.34 (95% CI 1.18-1.52) and 1.33 (95% CI 1.12-1.57) for ≥ 2 versus < 2 h physiotherapy, and 1.11 (95% CI 1.08-1.15) and 1.10 (95% CI 1.05-1.15) for an additional 30-min of physiotherapy. Physiotherapy type was not associated with discharge. CONCLUSION: We report an association between physiotherapy and discharge after hip fracture. An average UK hospital admitting 375 patients annually may save 456 bed-days if current provision increased so all patients with hip fracture received physiotherapy on 6-7 days in the first postoperative week. A 7-day physiotherapy service totalling at least 2 h in the first postoperative week may be considered a key performance indicator of acute care quality after hip fracture.

Infrared flashing light through the cricothyroid membrane to guide flexible bronchoscopic tracheal intubation.

Flexible bronchoscopic tracheal intubation is a fundamental technique in the management of the difficult airway but requires specific skills which may be both difficult to achieve and maintain. Therefore, techniques to improve its success should be developed. We present two cases, one where the ear, nose and throat surgeon could not view the glottis due to laryngeal pathology, and one where pathology in the oropharynx obscured access to the trachea during attempts at flexible bronchoscopic and videolaryngoscopic tracheal intubation. In both cases, tracheal intubation was subsequently successful due to the use of the Infrared Red Intubation System. This is an infrared light source that is secured to the anterior neck. It emits a flashing infrared light that is captured by the flexible bronchoscope, thus guiding the way to the trachea. These are the first reports of this technology being used for flexible bronchoscopic tracheal intubation in patients with severe airway pathology where conventional approaches had failed. Both cases emphasise that this technique can be of benefit in avoiding a surgical airway.

Observation of Microcanonical Atom Number Fluctuations in a Bose-Einstein Condensate.

Quantum systems are typically characterized by the inherent fluctuation of their physical observables. Despite this fundamental importance, the investigation of the fluctuations in interacting quantum systems at finite temperature continues to pose considerable theoretical and experimental challenges. Here we report the characterization of atom number fluctuations in weakly interacting Bose-Einstein condensates. Technical fluctuations are mitigated through a combination of nondestructive detection and active stabilization of the cooling sequence. We observe fluctuations reduced by 27% below the canonical expectation for a noninteracting gas, revealing the microcanonical nature of our system. The peak fluctuations have near linear scaling with atom number ΔN_{0,p}^{2}∝N^{1.134} in an experimentally accessible transition region outside the thermodynamic limit. Our experimental results thus set a benchmark for theoretical calculations under typical experimental conditions.

Exploring the limits of prolonged apnoea with high-flow nasal oxygen: an observational study.

High-flow nasal oxygen is increasingly used for oxygenation during apnoea. Extending apnoea duration using this technique has mainly been investigated during minor laryngeal surgery, but it is unclear how long it can be administered for before it should be discontinued due to acidosis. We aimed to describe the dynamics of arterial blood gases during apnoeic oxygenation with high-flow nasal oxygen with jaw thrust only, to explore the limits of this technique. We included adult orthopaedic patients scheduled for general anaesthesia. After pre-oxygenation, anaesthesia with neuromuscular blockade was induced and high-flow nasal oxygen (70 l.min-1 ) was continued with jaw thrust as the only means of airway management, with monitoring of vital signs and arterial blood gas sampling every 5 minutes. Apnoeic oxygenation with high-flow nasal oxygen was discontinued when arterial carbon dioxide tension (PaCO2 ) exceeded 12 kPa or pH fell to 7.15. This technique was used in 35 patients and median (IQR [range]) apnoea time was 25 (20-30 [20-45]) min and was discontinued in all patients when pH fell to 7.15. The mean (SD) PaCO2 increase was 0.25 (0.06) kPa.min-1 but it varied substantially (range 0.13-0.35 kPa.min-1 ). Mean (SD) arterial oxygen tension was 48.6 (11.8) kPa when high-flow nasal oxygen was stopped. Patients with apnoea time > 25 minutes were significantly older (p = 0.025). We conclude that apnoeic oxygenation with high-flow nasal oxygen resulted in a significant respiratory acidosis that varies substantially on the individual level, but oxygenation was maintained.

Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives.

Psilocybin is a tryptamine-derived psychoactive alkaloid found mainly in the fungal genus Psilocybe, among others, and is the active ingredient in so-called "magic mushrooms". Although its notoriety originates from its psychotropic properties and popular use as a recreational drug, clinical trials have recently recognized psilocybin as a promising candidate for the treatment of various psychological and neurological afflictions. In this work, we demonstrate the de novo biosynthetic production of psilocybin and related tryptamine derivatives in Saccharomyces cerevisiae by expression of a heterologous biosynthesis pathway sourced from Psilocybe cubensis. Additionally, we achieve improved product titers by supplementing the pathway with a novel cytochrome P450 reductase from P. cubensis. Further rational engineering resulted in a final production strain producing 627 ± 140 mg/L of psilocybin and 580 ± 276 mg/L of the dephosphorylated degradation product psilocin in triplicate controlled fed-batch fermentations in minimal synthetic media. Pathway intermediates baeocystin, nor norbaeocystin as well the dephosphorylated baeocystin degradation product norpsilocin were also detected in strains engineered for psilocybin production. We also demonstrate the biosynthetic production of natural tryptamine derivative aeruginascin as well as the production of a new-to-nature tryptamine derivative N-acetyl-4-hydroxytryptamine. These results lay the foundation for the biotechnological production of psilocybin in a controlled environment for pharmaceutical applications, and provide a starting point for the biosynthetic production of other tryptamine derivatives of therapeutic relevance.

Early secondary repair of obstetric anal sphincter injury: postoperative complications, long-term functional outcomes, and impact on quality of life.

BACKGROUND: An early secondary repair of the anal sphincter may be necessary if primary repair of obstetric anal sphincter injury (OASIS) is complicated by wound rupture or severe infection. The objective of this study was to assess the long-term functional outcomes, morbidity, and impact on quality of life (QoL) following an early secondary repair of OASIS. METHODS: This retrospective cohort study was conducted at Aarhus University Hospital, Denmark. All women having a secondary repair of the anal sphincter within 21 days of delivery from February 1991 to February 2017 were included (n = 51). Complications were assessed by reviewing medical records. The patient-reported outcomes were assessed in 2018 by questionnaires. Primary outcome was Wexner score and St. Mark's score. Impact on QoL was assessed using the Fecal Incontinence Quality of Life Scale (FIQLS). RESULTS: After a median follow-up time of 6.7 years (IQR 3.3-16.6), 34 women completed the questionnaire. The mean (SD) Wexner score was 5.2 ± 4.7 and the mean (SD) St. Mark's score was 6.8 ± 5.7. Women with a Wexner score ≥ 9 had a significantly lower QoL score in all domains of the FIQLS compared to women with a Wexner score < 9 (p < 0.001). Postoperative complications were experienced by 37%. Ten women developed a fistula of which nine required surgical treatment. CONCLUSIONS: An early secondary repair of the anal sphincter can be performed within 21 days of delivery with functional long-term outcomes comparable to those following a late sphincter repair. However, there is an imminent risk of complications, mainly fistulas, which should be taken into consideration when choosing the ideal timing of the repair.

Secondary sphincter repair for anal incontinence following obstetric sphincter injury: functional outcome and quality of life at 18 years of follow-up.

AIM: Secondary sphincter repair has been the conventional management of anal incontinence (AI) when a structural defect in the sphincter is recognized. However, disappointing long-term results have contributed to a tendency towards an increasing use of alternative treatment methods. This study aimed to assess the long-term functional outcomes following a secondary sphincter repair in women with AI after obstetric sphincter injury. METHOD: This is a questionnaire study of women who underwent a secondary sphincter repair in Denmark between January 1990 and December 2005. Patients were identified through the Danish National Patient Registry. Functional outcomes were assessed by a self-administered questionnaire in 2010 and 2018. Primary outcomes were Wexner and St. Mark's scores. Impact on quality of life was assessed using the Fecal Incontinence Quality of Life Scale. RESULTS: Functional outcome was assessed in 370 women in 2010 and 255 women in 2018. At 18.3 [interquartile range (IQR 15.0-22.0)] years of follow-up, the mean ± SD Wexner score was 8.8 ± 4.8 and the mean St. Mark's score was 11.7 ± 5.0. Flatus incontinence was the most frequent symptom, reported by 97%. Incontinence for liquid and solid stools was reported by 75% and 54%, respectively. There were no significant changes in incontinence frequencies over time. Women with a Wexner score of ≥ 9 had a significantly lower quality of life score in all domains than did women with a Wexner score of < 9 (P < 0.001). CONCLUSION: At long-term follow-up, few patients are fully continent following a secondary sphincter repair. However, it appears that the functional results remain stable at very long-term follow-up.

Relationship between patient and physician-rated xerostomia and dose distribution to the oral cavity and salivary glands for head and neck cancer patients after radiotherapy.

Introduction: Xerostomia is a frequent complication after curative intended radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC). Assessment of xerostomia is commonly done by the physician. The aim of this study is to investigate the relation between patient and physician-rated xerostomia and to predict the degree of xerostomia from patients with self-reported xerostomia based on delivered doses to the oral cavity, parotid, and submandibular glands. Material and methods: During a 2-year period, consecutive HNSCC patients attending the follow-up clinic were included. All included patients had self-reported xerostomia, and completed the disease-specific EORTC QLQ-H&N35 questionnaire. The physician assessed the degree of xerostomia with the DAHANCA toxicity scale and was blinded for the EORTC score. Oral cavity, parotid, and submandibular glands (OAR) were delineated on the planning CT according to international guidelines. DVH were extracted from treatment plans. Logistic regression tested the relation between mean doses, patient characteristics, and xerostomia scores. Differences between DVH values and scoring of xerostomia were analyzed with a Kruskal-Wallis test. The relation between xerostomia and dose distributions was further investigated using principal component analysis (PCA). Results: In total, 109 patients were included in the study. A weak correlation was seen between patient and physician-rated toxicity (p = .001), however, in general patients reported more toxicity than physicians. For EORTC score ≥2, the multi-variable analysis was significant for doses to the oral cavity, tobacco status and use of xerogenic medication. Neither the DVH analysis nor the PCA found any clear distinction between xerostomia scores for EORTC or DAHANCA and investigated OARs. Conclusion: Patients tended to report higher scores of xerostomia than the physician. PCA indicated a complex relation between doses to the OAR and xerostomia scores, showing e.g., that reducing doses in one organ was on the expense of increased dose to another organ.

Observation of Atom Number Fluctuations in a Bose-Einstein Condensate.

Fluctuations are a key property of both classical and quantum systems. While the fluctuations are well understood for many quantum systems at zero temperature, the case of an interacting quantum system at finite temperature still poses numerous challenges. Despite intense theoretical investigations of atom number fluctuations in Bose-Einstein condensates, their amplitude in experimentally relevant interacting systems is still not fully understood. Moreover, technical limitations have prevented their experimental investigation to date. Here we report the observation of these fluctuations. Our experiments are based on a stabilization technique, which allows for the preparation of ultracold thermal clouds at the shot noise level, thereby eliminating numerous technical noise sources. Furthermore, we make use of the correlations established by the evaporative cooling process to precisely determine the fluctuations and the sample temperature. This allows us to observe a telltale signature: the sudden increase in fluctuations of the condensate atom number close to the critical temperature.

Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial.

Postoperative delirium is common after hip fracture surgery, and may have a neuro-inflammatory cause. We conducted a single-centre, randomised, double-blind, placebo-controlled trial of 117 older hip fracture patients to see if a single, pre-operative intravenous dose of 125 mg methylprednisolone could reduce the severity and/or incidence of postoperative delirium, assessed using the Confusion Assessment Method delirium severity score. Modified intention-to-treat analysis found no significant difference in our primary outcome, median (IQR [range]) cumulative Confusion Assessment Method delirium severity score over the first three postoperative days between the methylprednisolone and placebo groups (1 (0-6 [0-39]) vs. 2 (0-10 [0-32]), p = 0.294). Both the prevalence of postoperative delirium (Confusion Assessment Method delirium severity score ≥ 5, 10/59 vs. 19/58, p = 0.048) and the median (IQR [range]) cumulated postoperative (by day 3) fatigue scores (5 (2-6 [0-11]) vs. 6 (4-8 [0-16]), p = 0.008) were significantly lower in the methylprednisolone compared with the placebo group. There were no significant between-group differences in the rate of completing physiotherapy, postoperative pain, the administration of antipsychotic drugs, infection, length of inpatient stay or 30- and 90-day mortality. No major adverse reactions related to methylprednisolone were recorded. We conclude that a single, pre-operative dose of 125 mg methylprednisolone does not reduce the severity of postoperative delirium, but may reduce both the prevalence of delirium and the severity of fatigue after hip fracture surgery in older patients, enabling remobilisation and recovery.

Obesity leads to impairments in the morphology and organization of human skeletal muscle lipid droplets and mitochondrial networks, which are resolved with gastric bypass surgery-induced improvements in insulin sensitivity.

AIMS: Skeletal muscle lipid stores and mitochondrial function have been appointed as key players in obesity-induced insulin resistance. However, there are conflicting reports in the literature based on in vitro quantitative measurements. Here, we test the hypothesis that it is not the quantity but the quality that matters. METHODS: This study combines quantitative and qualitative structural measurements of lipid stores and mitochondrial dynamics in skeletal muscle from lean subjects, and subjects with morbid obesity, with and without type 2 diabetes, before and after gastric bypass surgery. RESULTS: The structural organization of muscle mitochondrial networks in type II muscle fibres from subjects with morbid obesity is impaired. In addition, the amount of skeletal muscle perilipin 2 protein per intramyocellular lipid is reduced in subjects with morbid obesity, resulting in qualitative alterations in perilipin 2 coat around some lipid droplets. Gastric bypass surgery-induced weight loss and insulin resistance remission were associated with decreases in intramyocellular lipid stores and, qualitative improvements in lipid droplets' morphology, perilipin 2 coat and mitochondrial dynamics. CONCLUSION: Morbid obesity leads to severe qualitative alterations of both skeletal muscle lipid stores and mitochondrial networks. The degree of structural improvements after gastric bypass surgery was proportional to the improvements in whole body insulin sensitivity, suggesting an association between these events.

One-carbon metabolism markers are associated with cardiometabolic risk factors.

BACKGROUND AND AIMS: Alterations to one-carbon metabolism, especially elevated plasma homocysteine (Hcy), have been suggested to be both a cause and a consequence of the metabolic syndrome (MS). A deeper understanding of the role of other one-carbon metabolites in MS, including s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), and the methylation capacity index (SAM:SAH ratio) is required. METHODS AND RESULTS: 118 men and women with MS-risk factors were included in this cross-sectional study and cardiometabolic outcomes along with markers of one-carbon metabolism, including fasting plasma SAM, SAH, Hcy and vitamin B12 concentrations, were analysed. Multiple linear regression models were also used to examine the association between plasma one-carbon metabolites and cardiometabolic health features. We found that fasting plasma concentrations of Hcy, SAM and SAH were all positively correlated with markers of adiposity, including BMI (increase in BMI per 1-SD increase in one-carbon metabolite: 0.92 kg/m2 95% CI (0.28; 1.56), p = 0.005; 0.81 (0.15; 1.47), p = 0.02; 0.67 (-0.01; 1.36), p = 0.05, respectively). Hcy, but not SAM, SAH or SAM:SAH ratio was associated with BMI and body fat percentage after mutual adjustments. SAM concentrations were associated with higher fasting insulin (9.5% 95% CI (0.3; 19.5) per SD increase in SAM, p = 0.04), HOMA-IR (10.8% (0.8; 21.9), p = 0.03) and TNF-α (11.8% (5.0; 19.0), p < 0.001). CONCLUSION: We found little evidence for associations between SAM:SAH ratio and cardiometabolic variables, but higher plasma concentrations of SAM, SAH and Hcy are related to an overall higher risk of metabolic dysfunctions. The studies were registered at www.clinicaltrials.gov (NCT01719913 &NCT01731366).

A new retrograde transillumination technique for videolaryngoscopic tracheal intubation.

This single-centre, prospective trial was designed to assess the efficacy of a new retrograde transillumination device called the 'Infrared Red Intubation System' (IRRIS) to aid videolaryngoscopic tracheal intubation. We included 40 adult patients, who were undergoing elective urological surgery under general anaesthesia. We assessed the ability to differentiate the transilluminated glottis from other structures and found a median (IQR [range]) larynx recognition time of 8 (5-14 [3-28]) s. The difference in laryngeal visibility on the screen between the deactivated vs. activated device expressed on a visual analogue scale was significant (6 (4-7 [2-10]) vs. 10 (8-10 [4-10]); p < 0.001). The number of laryngoscope insertions was 1 (1-2 [1-3]) and the device showed high values on a visual analogue scale ranging from 0 (lowest score) to 10 (highest score) for helpfulness (6 (5-7 [2-10])), credibility (10 (8-10 [5-10])) and ease of use (10 (9-10 [8-10])). Tracheal intubation with the system lasted 26 (16-32 [6-89]) s. No alternative technique of securing the airway was necessary. The lowest SpO2 during intubation was 98 (97-99 [91-100])%. We conclude that this method of retrograde transillumination can assist videolaryngoscopy.

Sleep patterning changes in a prenatal stress model of depression.

Clinical depression is accompanied by changes in sleep patterning, which is controlled in a circadian fashion. It is thus desirable that animal models of depression mirror such diurnally-specific state alterations, along with other behavioral and physiological changes. We previously found several changes in behavior indicative of a depression-like phenotype in offspring of rats subjected to repeated, variable prenatal stress (PNS), including increased locomotor activity during specific periods of the circadian cycle. We, therefore, investigated whether PNS rats also exhibit alterations in sleep/wakefulness behavior around the change from light-to-dark phase. Control and PNS Sprague-Dawley rats were implanted with electrodes for continuous monitoring of electroencephalic activity used to determine behavioral state. The distribution of slow-wave sleep (SWS), rapid eye movement sleep (REMS) and wakefulness was compared for periods before and after lights were turned off, between baseline conditions and after exposure to an acute stressor. Both REMS and SWS amounts were increased in PNS rats relative to control animals in the beginning of the dark phase. REMS changes were due to an increase in REMS bout number, rather than in bout duration. During this circadian time period, we did not find any sex differences in the state changes. These results indicate that PNS affects baseline sleep patterning in both male and female rats around active-phase onset.

Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review.

Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19. The 22 studies included in the review (from a total of 1281 identified records) show that the behavioral phenotype of the ClockΔ19 mouse is characterized by hyperactivity, decreased anxiety-like behavior, decreased depression-like behavior and increased preference for rewarding stimuli. This is highly consistent with mania in humans. Moreover, the ClockΔ19 mouse exhibits rapid mood cycling (a manic-like phenotype during the day followed by euthymia at night), which is consistent with BD. Chronic administration of lithium, a drug with well established mood-stabilizing effect in humans with BD, reverses the majority of the bipolar-like traits and most of the neurobiological abnormalities observed in the ClockΔ19 mouse. In conclusion, the ClockΔ19 mouse has substantial face validity as an animal model for BD. The predictive validity of the ClockΔ19 mouse has primarily been investigated via studies using lithium challenge. Therefore, further studies are needed to determine how the ClockΔ19 mouse responds to other mood-stabilizing treatments of BD such as valproate, lamotrigine, carbamazepine, oxcarbazepine, antipsychotics, electroconvulsive therapy and various light interventions.