Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

BACKGROUND: Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. METHODS: The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. RESULTS: The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." CONCLUSION: Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

[High lithium serum level as maintenance treatment of rapid cycling bipolar disorder]. / Hoge lithiumspiegel als onderhoudsbehan­deling van rapid cycling bipolaire stoornis.

Bipolar disorder with a rapid cycling course can be difficult to treat, often involving therapy resistance. A 55-year old patient with bipolar disorder with rapid cycling course did not stabilize for years, despite various pharmacotherapeutic treatments. Only after lithium was introduced as a maintenance treatment at a level of around 1.20 mmol/l, a long-term stabilization of mood developed which also persisted. A literature review was performed which concluded that maintenance treatment with lithium at levels above 1.0 mmol/l in patients with rapid cycling bipolar disorder has not been adequately studied.

Associations between physical fitness and cardiovascular disease in older adults with intellectual disabilities: Results of the Healthy Ageing and Intellectual Disability study.

BACKGROUND: Reduced physical fitness is a cardiovascular disease (CVD) risk factor in the general population. However, generalising these results to older adults with intellectual disabilities (ID) may be inappropriate given their pre-existing low physical fitness levels and high prevalence of co-morbidities. Therefore, the aim of this study is to investigate the difference in physical fitness between older adults with ID with and without CVD. METHOD: Baseline data of a cohort of older adults with borderline to profound ID (HA-ID study) were used (n = 684; 61.6 ± 8.2 years; 51.3% male). CVD status (coronary artery disease, heart failure, stroke) was obtained from medical files. Cardiorespiratory fitness (10-m incremental shuttle walking test), comfortable and fast gait speed (over 5 m distance) and grip strength (hand dynamometer) were measured. Multivariable linear regression models were used to investigate the association between these physical fitness components and the presence of CVD, adjusted for participant characteristics. RESULTS: Of the 684 participants 78 (11.4%) had CVD. Participants with CVD scored lower on cardiorespiratory fitness (-81.4 m, P = 0.002), comfortable gait speed (-0.3 km/h, P = 0.04) and fast gait speed (-1.1 km/h, P = 0.04). No significant differences were found for grip strength (-0.2 kg, P = 0.89). CONCLUSIONS: Older adults with CVD had significantly lower physical fitness levels than those without CVD, except for grip strength. Longitudinal research is needed to investigate causality.

The long-term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review.

BACKGROUND: Progesterone is widely used in prenatal care. However, long-term effects of prenatal progesterone treatment on child development are unclear. OBJECTIVES: To evaluate long-term outcomes in children after prenatal progesterone treatment. SEARCH STRATEGY: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. MAIN RESULTS: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta-analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley-III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference -0.04, 95% Confidence Interval -0.26 to 0.19), I2  = 22%. Heterogeneity prohibited additional meta-analyses. Other long-term outcomes showed no differences. CONCLUSIONS: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow-up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. TWEETABLE ABSTRACT: Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear.

Characteristics of helicopter emergency medical services (HEMS) dispatch cancellations during a six-year period in a Dutch HEMS region.

BACKGROUND: For decades, Helicopter Emergency Medical Services (HEMS) contribute greatly to prehospital patient care by performing advanced medical interventions on-scene. Unnecessary dispatches, resulting in cancellations, cause these vital resources to be temporarily unavailable and generate additional costs. A previous study showed a cancellation rate of 43.5% in our trauma region. However, little recent data about cancellation rates and reasons exist, despite revision of dispatch protocols. This study examines the current cancellation rate in our trauma region over a six-year period. Additionally, cancellation reasons are evaluated per type of dispatch and initial incident report, upon which HEMS is dispatched. METHODS: This retrospective study analyzed the data of the Dutch HEMS Lifeliner 1 (North-West region of the Netherlands, covering a population of 5 million inhabitants), analyzing all subsequent cases between April 1st 2013 and April 1st 2019. Patient characteristics, type of dispatch (primary; based on dispatcher criteria versus secondary, as judged by the first ambulance team on site), initial incident report received by the EMS dispatch center, and information regarding day- or nighttime dispatches were collected. In case of cancellation, cancel rate and reason per type of dispatch and initial incident report were assessed. RESULTS: In total, 18,638 dispatches were included. HEMS was canceled in 54.5% (95% CI 53.8-55.3%) of cases. The majority of canceled dispatches (76.1%) were canceled because respiratory, hemodynamic, and neurologic parameters were stable. Dispatches simultaneously activated with EMS (primary dispatch) were canceled in 58.3%, compared to 15.1% when HEMS assistance was requested by EMS based on their findings on-scene (secondary dispatch). A cancellation rate of 54.6% was found in trauma related dispatches (n = 12,148), compared to 52.2% in non-trauma related dispatches (n = 5378). Higher cancellation rates exceeding 60% were observed in the less common dispatch categories, e.g., anaphylaxis (66.3%), unknown incident report (66.0%), assault with a blunt object (64.1%), obstetrics (62.8%), and submersion (61.9%). CONCLUSION: HEMS cancellations are increased, compared to previous research in our region. Yet, the cancellations are acceptable as the effect on HEMS' unavailbility remains minimized. Focus should be on identifying the patient in need of HEMS care while maintaining overtriage rates low. Continuous evaluation of HEMS triage is important, and dispatch criteria should be adjusted if necessary.

[Clozapine treatment and COVID-19: continue despite leukocytopenia and increase of clozapine serum levels]. / Clozapinebehandeling en COVID-19: doorgaan ondanks leukocytopenie en spiegelstijging.

Clozapine is an antipsychotic with clozapine-induced agranulocytosis (CIA) as a rare, but potentially life-threatening side-effect, for which the white blood cell count and absolute neutrophil count are routinely monitored. Observed leukopenia may lead to more frequent monitoring, or even acute discontinuation of clozapine treatment. COVID-19 may cause deviating blood parameters such as leukopenia, and more exceptionally even granulocytopenia, just as clozapine does. In case of a SARS-CoV-2 infection and leukopenia, it is important to differentiate whether the reduced white blood cell count is caused by clozapine - in which case it needs to be stopped immediately - or as a consequence of infection with the coronavirus. In case of a mild leukopenia, based on a lymphopenia, clozapine can be safely continued with more frequent blood monitoring. Additionally, the dosage of clozapine should be reduced by half, due to the risk of a sudden increase of clozapine serum levels.

[Earlier recognition of bipolar disorder - necessity and advice for clinical practice]. / Tijdige herkenning van bipolaire stoornissen; noodzaak en praktijkadviezen.

BACKGROUND: There is an average 10-year delay in diagnosing bipolar disorder, hampering the application of effective therapeutic interventions.
AIM: To investigate factors contributing to early recognition.
METHOD: We give a stage-oriented overview of the opportunities for early recognition.
RESULTS: Recognition in stage 0 (at-risk) and stage 1 (prodromal) is yet impossible. In stage 2 (syndromal) there are opportunities for better recognition in patients presenting with depression by conducting a thorough (collateral) psychiatric assessment, family history and by applying additional screening tools. CONCLUSIONS There are opportunities for better recognition of bipolar disorder in the syndromal stage.

A healthy dietary pattern is associated with microbiota diversity in recently diagnosed bipolar patients: The Bipolar Netherlands Cohort (BINCO) study.

BACKGROUND: Diet largely impacts the gut microbiota, and may affect mental and somatic health via the gut-brain axis. As such, the relationship between diet and the microbiota in Bipolar Disorder (BD) could be of importance, but has not been studied before. The aim was therefore to assess whether dietary quality is associated with the gut microbiota diversity in patients with recently diagnosed BD, and whether changes occur in dietary quality and microbiota diversity during their first year of treatment. METHODS: Seventy recently (<1 year) diagnosed patients with BD were included in the "Bipolar Netherlands Cohort" (BINCO), and a total of 45 participants were assessed after one year. A 203-item Food Frequency Questionnaire (FFQ) data yielded the Dutch Healthy index (DHD-15), and the microbiota composition and diversity of fecal samples were characterized by 16S rRNA gene amplicon sequencing at baseline and 1-year follow-up. Associations and changes over time were analyzed using multivariate regression analyses and t-tests for paired samples. RESULTS: Included patients had a mean age of 34.9 years (SD ± 11.2), and 58.6 % was female. Alpha diversity (Shannon diversity index), richness (Chao1 index) and evenness (Pielou's Evenness Index) were positively associated with the DHD-15 total score, after adjustment for sex, age and educational level (beta = 0.55; P < 0.001, beta = 0.39; P = 0.024, beta = 0.54; P = 0.001 respectively). The positive correlations were largely driven by the combined positive effect of fish, beans, fruits and nuts, and inverse correlations with alcohol and processed meats. No significant changes were found in DHD-15 total score, nor in microbiota diversity, richness and evenness indexes during one year follow-up and regular treatment. CONCLUSION: A healthy and varied diet is associated with the diversity of the microbiota in BD patients. Its potential consequences for maintaining mood stability and overall health should be studied further.

Prehospital accuracy of (H)EMS pelvic ring injury assessment and the application of non-invasive pelvic binder devices.

BACKGROUND: Pre-hospital application of a non-invasive pelvic binder device (NIPBD) is essential to increase chances of survival by limiting blood loss in patients with an unstable pelvic ring injury. However, unstable pelvic ring injuries are often not recognized during prehospital assessment. We investigated the prehospital (helicopter) emergency medical services ((H)EMS)' accuracy of the assessment of unstable pelvic ring injuries and NIPBD application rate. METHODS: We performed a retrospective cohort study on all patients with a pelvic injury transported by (H)EMS to our level one trauma centre between 2012 and 2020. Pelvic ring injuries were included and radiographically categorized using the Young & Burgess classification system. Lateral Compression (LC) type II/III -, Anterior-Posterior (AP) type II/III - and Vertical Shear (VS) injuries were considered as unstable pelvic ring injuries. (H)EMS charts and in-hospital patient records were evaluated to determine the sensitivity, specificity and diagnostic accuracy of the prehospital assessment of unstable pelvic ring injuries and prehospital NIPBD application. RESULTS: A total of 634 patients with pelvic injuries were identified, of whom 392 (61.8%) had pelvic ring injuries and 143 (22.6%) had unstable pelvic ring injuries. (H)EMS personnel suspected a pelvic injury in 30.6% of the pelvic ring injuries and in 46.9% of the unstable pelvic ring injuries. An NIPBD was applied in 108 (27.6%) of the patients with a pelvic ring injury and in 63 (44.1%) of the patients with an unstable pelvic ring injury. (H)EMS prehospital diagnostic accuracy measured in pelvic ring injuries alone was 67.1% for identifying unstable pelvic ring injuries from stable pelvic ring injuries and 68.1% for NIPBD application. CONCLUSION: The (H)EMS prehospital sensitivity of unstable pelvic ring injury assessment and NIPBD application rate is low. (H)EMS did not suspect an unstable pelvic injury nor applied an NIPBD in roughly half of all unstable pelvic ring injuries. We advise future research on decision tools to aid the routine use of an NIPBD in any patient with a relevant mechanism of injury.

Hepatitis B prevalence in the Turkish population of Arnhem: implications for national screening policy?

Despite the increased prevalence of hepatitis B and C in most migrant groups in The Netherlands, a national screening policy for these infections is not available. In order to estimate the prevalence of hepatitis B and C in the largest group of first-generation migrants (FGM) in The Netherlands, we conducted a screening project in the Turkish community of Arnhem. In a separate project we identified patients from the target population with chronic hepatitis B and C from hospital records (1990-2008). Educational meetings concerning hepatitis were organized, with all participants being offered a blood screening test. Participants were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc) and antibodies to hepatitis C virus (anti-HCV). In total 709 persons were tested, a complete dataset was available for 647 patients. We found that 3·0% and 0·4% of Turkish FGM aged >24 years in Arnhem had active hepatitis B, defined as HBsAg positive, and tested positive for anti-HCV, respectively. The hospital records revealed another 32 patients, 28 with hepatitis B and four with hepatitis C representing 0·7% for hepatitis B and 0·1% for hepatitis C in relation to the total number of Turkish FGM in Arnhem. We believe that active hepatitis screening of FGM from Turkey should be part of the national health policy as it will benefit the individual and public health.

Salivary markers of stress system activation and social withdrawal in humans.

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role. We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal. In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD = 12.8; 64.1% female). Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i.e., area under the curve with respect to the increase, beta = 0.082, p = 0.02; evening sC value: beta = 0.110, p = 0.003; and mean sC value: beta = 0.097; p = 0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression. Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPA-axis activation may partly aggravate social withdrawal in depressive disorders.

Personality traits and the risk of incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders in a 9-year cohort study.

BACKGROUND: Bipolar disorder (BD) is characterized by the alternating occurrence of (hypo)manic and depressive episodes. The aim of the current study was to determine whether personality traits independently predicted the subsequent development of (hypo)manic episodes within a group of patients who were initially diagnosed with depressive and anxiety disorders. METHODS: The Netherlands Study of Depression and Anxiety is a cohort study with measurements taken at baseline and at 2-, 4-, 6-, and 9-year follow-up. Development of a (hypo)manic episode during follow-up was assessed with the Composite International Diagnostic Interview and (hypo)manic symptoms were evaluated with the Mood Disorder Questionnaire. The Big Five personality traits were the independent variables in multivariable Cox regression analyses. RESULTS: There were 31 incident cases of (hypo)manic episodes (n = 1888, mean age 42.5 years, 68.3% women), and 233 incident cases of (hypo)manic symptoms (n = 1319, mean age 43.1, 71.9% women). In multivariable analyses, low agreeableness was independently associated with an increased risk of developing a (hypo)manic episode, with a hazard ratio (HR) of 0.54 (p = 0.002, 95% CI [0.37, 0.78]). This finding was consistent with the development of (hypo)manic symptoms (HR 0.77, p = 0.001, 95% CI [0.66, 0.89]). LIMITATIONS: The 2-year lag-time analysis reduced the number of participants at risk of a (hypo)manic episode. CONCLUSIONS: We conclude that low agreeableness is a personality-related risk factor for incident (hypo)mania among subjects initially suffering from depressive and anxiety disorders. Increased attention to personality deviances could help to recognize BD at an early stage.

Psoas compartment block for lower extremity surgery: a meta-analysis.

Psoas compartment block (PCB) is a potentially useful but controversial technique for lower limb surgery. We have conducted a systematic review of the efficacy and safety of PCB for anaesthesia and postoperative analgesia for hip and knee surgery. Relevant studies were identified within PubMed, EMBASE, and the Cochrane Library. The main outcome measure for anaesthesia was anaesthetic efficacy. For postoperative analgesia, the severity of postoperative pain was compared. The data were subjected to meta-analysis using relative risks with 95% confidence intervals (95% CI) for dichotomous variables and weighted mean differences with 95% CI for continuous variables. Thirty publications were included. PCB is an effective intervention for analgesia after hip and knee surgery. It appears superior to opioids for pain relief after hip surgery. This analgesic benefit may be extended beyond 8 h by the use of a catheter technique. Compared with Winnie's 3-in-1 block, PCB is associated with more consistent block of the obturator nerve. PCB may be an alternative to postoperative neuraxial block. Although PCB combined with sciatic nerve block and sedation is an effective technique for minor knee surgery, there is currently insufficient data to recommend the use of this approach for hip and major knee surgery. PCB is a safe and effective alternative for analgesia after hip and knee surgery. More research is required to define its role in the intraoperative setting and confirm potentially beneficial effects on variables such as perioperative haemodynamics and blood loss.

Elevated salivary alpha-amylase levels at awakening in patients with depression.

BACKGROUND: Specific Major Depressive Disorder (MDD) biomarkers could help improve our understanding of MDD pathophysiology and aid in the refinement of current MDD criteria. While salivary cortisol (SC) can differentiate between healthy controls and patients with psychiatric disorders, salivary alpha amylase (sAA), may be a putative candidate biomarker for MDD specifically. METHODS: In a naturalistic cohort of consecutive out-patients and healthy controls, sAA and SC were determined in 833 participants (97 MDD patients, 142 patients with other mood, anxiety, and/or somatoform (MAS-) disorders, and 594 healthy controls). Samples were collected at 7 different time points (at awakening, after 30, 45, and 60 min, at 10:00 p.m., at 11:00 p.m., and at awakening on day 2). RESULTS: The mean age of the sample was 43.8 years (SD = 12.9; 63.9% female). Concerning sAA, MDD patients had higher sAA levels upon awakening on two consecutive days (p = 0.04, p = 0.01 respectively), as well as a higher area under the curve with respect to the increase (AUCi; p = 0.04) in comparison to both controls and the other MAS-disorders group. Regarding SC, mean levels of evening SC were elevated in MDD patients (p = 0.049) in comparison to both controls and the other MAS-disorders group. SC values on day 2 after ingestion of dexamethasone were elevated in both MDD patients and the other MAS-disorders group (p = 0.04, p = 0.047 respectively). CONCLUSIONS: sAA at awakening and not cortisol differentiates MDD from other psychiatric disorders in outpatients. This suggests that sAA may be a valuable candidate biomarker specifically for MDD.

A Descriptive Mixed-Methods Analysis of Sexual Behavior and Knowledge in Very Young Children Assessed for Sexual Abuse: The ASAC Study.

Child sexual abuse (CSA) is a worldwide problem with serious consequences. We hypothesized that worrisome sexual behavior and knowledge would frequently be reported in children assessed after CSA. We therefore investigated (A) what types of sexual behaviors and knowledge were reported by parents of young children assessed for CSA; (B) in what cases such behaviors and knowledge were worrisome; and (C) how such children responded verbally and non-verbally during child interviews. We conducted a mixed-methods study, including qualitative inductive content analysis and quantitative analysis. It included 125 children (76 boys, 60.8%; median age 3.3 years, age range 0-11), all involved in the Amsterdam sexual abuse case (ASAC) and examined for highly suspected (n = 71) or confirmed CSA (n = 54). We identified themes from (1) the parent reports: sexual behavior (e.g., self-stimulation, touching others, imitation of sexual acts), fears and anxiety with regard to sexuality, and sexual utterances (sexual slang, references to sexual acts); and (2) the child interviews: behavioral reactions (avoidance, distractive behaviors), emotional reactions (anger, aggression), and verbal reactions (conspicuous utterances, refusal to talk about specific subjects). In 37% of the children the sexual behavior was deemed worrisome or very worrisome. Clinicians who assess children for CSA are advised to focus in particular on sexual behavior problems and inappropriate sexual knowledge.