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Background and objective The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients. Methods Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach. Results Pain2D was able to classify the four rare diseases with an accuracy of 61–77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%. Conclusions Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.

IntroductionPostoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life.Methods and analysisThis is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p<0.05.Ethics and disseminationElectroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) is approved by the ethics board at Washington University. Recruitment began in January 2015. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media.Trial registration numberNCT02241655; Pre-results.

Die Osteoporose ist weltweit eine häufige Erkrankung, bei der eine Verminderung der Knochendichte zu einem erhöhten Frakturrisiko und einer Verringerung der Körpergröße führen kann. Die Osteoporose ist mit akuten wie auch chronischen Schmerzen assoziiert, die vor allem im Rücken auftreten und die Lebensqualität deutlich einschränken können. Soll betroffenen Patienten adäquat geholfen werden, ist es essenziell, die Besonderheiten der Schmerztherapie bei Osteoporose zu kennen, beispielsweise spezielle Möglichkeiten der medikamentösen und nichtmedikamentösen Behandlung. Dieser Beitrag gibt einen umfassenden Überblick über die zeitgemäße Schmerztherapie bei Osteoporose und erläutert darüber hinaus die zugrunde liegenden Pathomechanismen, Risikofaktoren und das reguläre diagnostische Vorgehen.

HintergrundDer Zugang zu Cannabisprodukten wird weltweit zunehmend liberalisiert. Es besteht ein großes Interesse an cannabisbasierten Medikamenten.Ziel der ÜbersichtDarstellung der aktuellen Studienlage zur Wirksamkeit von cannabisbasierten Medikamenten bei verschiedenen Erkrankungen.DatenlageArzneimittelrechtlich zugelassen sind zurzeit Nabiximols zur Behandlung einer mittelschweren bis schweren therapieresistenten Spastik bei multipler Sklerose sowie Nabilon zur Behandlung von therapieresistenter Übelkeit und Erbrechen unter einer Chemotherapie. Darüber hinaus kommt die Verwendung von Cannabinoiden als individueller Therapieversuch infrage, wenn es bei chronischen Schmerzen (neuropathischen Schmerzen, Tumor- und nichtneuropathischen Schmerzen, nichtkrebsassoziierten Schmerzen), bei Human-immunodeficiency-virus-assoziierter Kachexie bzw. beim Dravet- oder Lennox-Gastaut-Syndrom zu einem Therapieversagen gekommen ist. Aus Sicht der Autoren besteht für die Indikationen chemotherapieassoziierte Übelkeit und Erbrechen sowie nichtneuropathischer chronischer Schmerz keine ausreichende Evidenz.SchlussfolgerungEine breite Anwendung von Cannabinoiden ist aktuell nicht absehbar. Weitere Studien mit höheren Patientenzahlen und zu den Langzeitauswirkungen einer Cannabinoidtherapie sind notwendig.

When more fully recognized, Lardner's contributions to American letters include adding a \"'mordant wit'\" (Silverman and Silverman 387) to humor writing, conveying the unique American vernacular as a craftsman of the short story and an innovator in sports writing, satirizing the naive American abroad, and devising hilariously absurd plays.2 To this list of literary accomplishments should be added Lardner's writing about the First World War, which scholars have only recently made more available. Skeptical of an overly shaped \"reality,\" especially if it defied actual human experience and impulse, Lardner directed his humor at false ideas about the war while maintaining overall support for it. In addition to such overt support for the U.S. war effort, Lardner offers more subtle endorsement. In \"Society Does Its Bit,\" published on April 26, 1917, he mocked wealthy people ostentatiously \"doing their bit\" for the war effort: G. Worthington Smith-Smith-Smith. 1126 West Randolph, announced that he would donate his share of the County Hospital to America and its new allies.

Study Objectives: Delirium is a postoperative complication accompanied by disturbances in attention, cognition, arousal, and psychomotor activity. Wrist actigraphy has been advocated to study inactivity and inferred sleep patterns during delirium. We hypothesized that altered patterns of motor activity or immobility, reflective of disordered sleep and wakefulness patterns, would serve as predictive markers of hypoactive postoperative delirium. Methods: Eighty-four elderly surgical patients were classified into three groups based on the timing of hypoactive delirium following surgery: intact with no delirium throughout postoperative days (POD) 0–5 (n = 51), delirium during POD 0–1 (n = 24), and delirium during POD 2–5 (n = 13). Delirium was detected on daily Confusion Assessment Method evaluations and chart review. Actigraphy measures were calculated from accelerometry signals acquired on the first postoperative day (POD 0, 16:00–23:00) and night (POD 0, 23:00–POD 1, 06:00). Results: Actigraphy metrics showed substantial interpatient variability. Among the three patient groups, only those without delirium showed greater movement during the day compared to night and also fewer minutes of night immobility ( P = .03 and P = .02, Wilcoxon rank-sum tests). These patients were poorly discriminated from those with delirium during either POD 0–1 or POD 2–5, using differences in day and night activity (C-statistic, 95% confidence interval [CI]: 0.66 [0.53–0.79] and C-statistic, 95% CI: 0.71 [0.55–0.87], respectively). Inclusion of low-frequency signals improved performance of immobility measures without affecting those based on activity. Cognitively intact patients during POD 0–5 were distinguished from those with delirium during POD 0–1, based on differences in the number of day and night immobile minutes (C-statistic 0.65, 95% CI: [0.53–0.78]). Actigraphy metrics with the strongest association to delirium incidence were not reliably correlated with an increased risk during POD 0–5, when accounting for patient age, sex, intensive care unit admission, and Charlson Comorbidity Index (adjusted odds ratio of 1.7, 95% CI: [1.0–3.0], P = .09, likelihood ratio test). Conclusions: Early postoperative wrist actigraphy metrics that serve as markers of sleep and wakefulness offer limited capacity as sole predictors or markers of hypoactive delirium. Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) Study; Identifier: NCT02241655; URL: https://clinicaltrials.gov/ct2/show/NCT02241655 Citation: Maybrier HR, King CR, Crawford AE, Mickle AM, Emmert DA, Wildes TS, Avidan MS, Palanca BJ; ENGAGES Study Investigators. Early postoperative actigraphy poorly predicts hypoactive delirium. J Clin Sleep Med 2019;15(1):79–87.

Herpes simplex virus infection is increasingly common in the US. New antiviral medications have expanded treatment options for the two most common cutaneous manifestations, orolabial and genital herpes.

Delirium is a common and serious postoperative complication. Subanaesthetic ketamine is often administered intraoperatively for postoperative analgesia, and some evidence suggests that ketamine prevents delirium. The primary purpose of this trial was to assess the effectiveness of ketamine for prevention of postoperative delirium in older adults. The Prevention of Delirium and Complications Associated with Surgical Treatments [PODCAST] study is a multicentre, international randomised trial that enrolled adults older than 60 years undergoing major cardiac and non-cardiac surgery under general anaesthesia. Using a computer-generated randomisation sequence we randomly assigned patients to one of three groups in blocks of 15 to receive placebo (normal saline), low-dose ketamine (0·5 mg/kg), or high dose ketamine (1·0 mg/kg) after induction of anaesthesia, before surgical incision. Participants, clinicians, and investigators were blinded to group assignment. Delirium was assessed twice daily in the first 3 postoperative days using the Confusion Assessment Method. We did analyses by intention-to-treat and assessed adverse events. This trial is registered with clinicaltrials.gov, number NCT01690988. Between Feb 6, 2014, and June 26, 2016, 1360 patients were assessed, and 672 were randomly assigned, with 222 in the placebo group, 227 in the 0·5 mg/kg ketamine group, and 223 in the 1·0 mg/kg ketamine group. There was no difference in delirium incidence between patients in the combined ketamine groups and the placebo group (19·45% vs 19·82%, respectively; absolute difference 0·36%, 95% CI −6·07 to 7·38, p=0·92). There were more postoperative hallucinations (p=0·01) and nightmares (p=0·03) with increasing ketamine doses compared with placebo. Adverse events (cardiovascular, renal, infectious, gastrointestinal, and bleeding), whether viewed individually (p value for each >0·40) or collectively (36·9% in placebo, 39·6% in 0·5 mg/kg ketamine, and 40·8% in 1·0 mg/kg ketamine groups, p=0·69), did not differ significantly across groups. A single subanaesthetic dose of ketamine did not decrease delirium in older adults after major surgery, and might cause harm by inducing negative experiences. National Institutes of Health and Cancer Center Support.

Bromate ion (BrO3–) in drinking water is a concern to water utilities because of its toxicity—but also because new regulations have been promulgated to lower residual levels of BrO3– in finished water. This study evaluated sulfite ion (SO32–) and reduced iron (Fe2+) as potential removal agents for BrO3–over a wide pH range. The experimental rate law for BrO3– removal using SO32– shows that the rate of removal decreases with increasing pH. The experimental rate law for BrO3– removal using Fe2+ shows that the rate of removal increases with increasing pH.