Generalized music therapy to reduce neuroactive drug needs in critically ill patients. Study protocol for a randomized trial.

BACKGROUND: Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh intensive care unit (ICU) environment. However, this pharmacological therapy presents several side effects: guidelines suggest using a light sedation target, keeping critically ill patients calm, conscious, and cooperative. Personalized music therapy (MT) can reduce stress and anxiety, decreasing the need for drugs. The aim of the current investigation is to compare different approaches for MT in the ICU: a personalized approach, with music selected by patients/families and listened through headphones, or a generalized approach, with ambient music chosen by a music therapist and transmitted through speakers. PRIMARY OUTCOME: number of days "free from neuroactive drugs" in the first 28 days after ICU admission. SECONDARY OUTCOMES: total amount of neuroactive drugs (midazolam, propofol, morphine, fentanyl, haloperidol), stress during ICU stay (sleep at night, anxiety and agitation, use of physical restraints, stressors evaluated at discharge), the feasibility of generalized MT (interruptions requested by staff members and patients/families). METHODS: Randomized, controlled trial with three groups of critically ill adults: a control group, without MT; a personalized MT group, with music for at least 2 h per day; a generalized MT group, with music for 12.5 h/day, subdivided into fifteen 50-min periods. DISCUSSION: One hundred fifty-three patients are expected to be enrolled. This publication presents the rationale and the study methods, particularly the strategies used to build the generalized MT playlist. From a preliminary analysis, generalized MT seems feasible in the ICU and is positively received by staff members, critically ill patients, and families. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03280329. September 12, 2017.

Milan's forgotten epidemic of summer 1629, a few months before the last great plague: An investigation into the possible cause.

An epidemic not attributable to plague caused thousands of deaths in Milan in the summer of 1629, a time of war and famine that immediately preceded the even more fatal Great Plague of 1630 that killed an estimated ten of thousands of people. The 5,993 deaths of 1629 recorded in the Liber Mortuorum of Milan (a city with an estimated population of 130,000 inhabitants at the time) were 45.7% more than the average number recorded between 1601 and 1628. Registered deaths peaked in July, and 3,363 of the deaths (56,1%) were attributed to a febrile illness which, in most cases (2,964, 88%), was not associated with a rash or organ involvement. These deaths involved 1,627 males and 1,334 females and occurred at a median age of 40 years (range 0-95). In this paper, we discuss the possible cause of the epidemic, which may have been an outbreak of typhoid fever.

Epitope recognition in the human-pig comparison model on fixed and embedded material.

The conditions and the specificity by which an antibody binds to its target protein in routinely fixed and embedded tissues are unknown. Direct methods, such as staining in a knock-out animal or in vitro peptide scanning of the epitope, are costly and impractical. We aimed to elucidate antibody specificity and binding conditions using tissue staining and public genomic and immunological databases by comparing human and pig-the farmed mammal evolutionarily closest to humans besides apes. We used a database of 146 anti-human antibodies and found that antibodies tolerate partially conserved amino acid substitutions but not changes in target accessibility, as defined by epitope prediction algorithms. Some epitopes are sensitive to fixation and embedding in a species-specific fashion. We also find that half of the antibodies stain porcine tissue epitopes that have 60% to 100% similarity to human tissue at the amino acid sequence level. The reason why the remaining antibodies fail to stain the tissues remains elusive. Because of its similarity with the human, pig tissue offers a convenient tissue for quality control in immunohistochemistry, within and across laboratories, and an interesting model to investigate antibody specificity.