Post-traumatic Stress Disorder Among COVID-19 Survivors at 3-Month Follow-up After Hospital Discharge.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe but treatable mental disorder that develops after a life-threatening traumatic event. Coronavirus disease 19 (COVID-19) hospitalisation is a potentially traumatic experience, especially in severe cases. Furthermore, the unprecedented context of the severe acute respiratory syndrome coronavirus 2 pandemic, with daily media bombardment about COVID-19 mortality, may have amplified life-threatening perception also in patients with moderate infection. The aim of this study was to assess the prevalence and risk factors of PTSD at 3-month follow-up in patients hospitalised for COVID-19 infection. DESIGN: In this cohort follow-up study conducted in a large Italian academic COVID-19 hospital, 115 recruited survivors were contacted by telephone 3 months after discharge to home care. The Posttraumatic Stress Disorder Checklist for DSM-5 was administered. Multivariate logistic regression models were used to analyse risk factors for the development of PTSD. KEY RESULTS: A total of 10.4% of the sample received a PCL-5-based diagnosis of PTSD. Other 8.6% of the sample received a diagnosis of subthreshold PTSD, which leads to significant levels of distress and impairment. Multivariate regression analysis indicated that previous psychiatric diagnosis (odds ratio (OR) = 6.3, 95% confidence interval (CI): 3.7-78.6, p < 0.001) and obesity (OR = 3.51, 95% CI: 1.4-857.9, p = 0.03) were risk factors for developing PTSD. Chronic pulmonary diseases approached significance as a risk factor (OR = 6.03, 95% CI: 1.0-37.1, p = 0.053). Male sex was a protective factor (OR=0.04, 95% CI: 0.0-0.041, p = 0.007). CONCLUSIONS: PTSD and subthreshold PTSD rates in patients hospitalised for COVID-19 are worrying. Female sex and pre-existing mental disorders are established risk factors for PTSD, while the prospective association with obesity needs further investigation. Clinicians treating COVID-19 should consider screening for PTSD at follow-up assessments in patients discharged from the hospital.

Xerostomia, gustatory and olfactory dysfunctions in patients with COVID-19.

BACKGROUND: The novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19. METHODS: This retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th. RESULTS: Taste dysfunction was the most common reported symptom (59.5%; n = 66), followed by xerostomia (45.9%; n = 51) and olfactory dysfunctions (41.4%; n = 46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5-10). Overall 74.5% (n = 38) of patients with xerostomia, 78.8% (n = 52) of patients with gustatory dysfunctions and 71.1% (n = 33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n = 51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time. CONCLUSION: Xerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus.

Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade.

Hypertension and type 2 diabetes mellitus (T2DM) are risk factors for cardiovascular disease. Dapagliflozin improves glycemic control and systolic blood pressure (SBP) in T2DM patients. This double-blind phase III study evaluated the effects of dapagliflozin on glycemic control and blood pressure in patients with inadequately controlled T2DM and hypertension, despite ongoing therapy with a renin-angiotensin system blocker. Patients were randomized to receive dapagliflozin 10 mg (n = 302) or placebo (n = 311) once daily for 12 weeks. Endpoints were change from baseline to week 12 in seated SBP and glycosylated hemoglobin (HbA1c); longitudinal repeated-measures analysis was performed. Additional endpoints included other hemodynamic measures, serum uric acid, fasting plasma glucose, body weight, blood lipids and heart rate. After 12 weeks, dapagliflozin-treated versus placebo-treated patients showed significant reductions in HbA1c (-0.6% vs -0.1%, p < 0.0001), mean seated SBP (-10.4 vs -7.3 mmHg, p = 0.0010) and mean 24 h ambulatory SBP (-9.6 vs -6.7 mmHg, p = 0.0043). Dapagliflozin also reduced body weight compared with placebo (-1.0 vs -0.3 kg). Dapagliflozin was well tolerated, with adverse events consistent with previous studies. Dapagliflozin improved glycemic control, and reduced SBP as well as body weight in patients with poorly controlled T2DM and hypertension.

Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects.

PURPOSE: Pre-clinical experiments have shown that almorexant, a dual orexin receptor antagonist, is able to inhibit cytochrome P450 3A4 (CYP3A4). Therefore, a study was conducted to investigate the effects of multiple-dose almorexant on the pharmacokinetics of midazolam and simvastatin, two CYP3A4 model substrates. METHODS: Fourteen healthy male subjects were enrolled in an open-label, randomized, two-way crossover study. Treatment period A consisted of a single oral dose of 2 mg midazolam on day 1 and 40 mg simvastatin on day 3. In treatment period B, subjects received 200 mg almorexant once daily for 9 days together with a single oral dose of midazolam on day 7 and simvastatin on day 9. RESULTS: Concomitant administration of midazolam with almorexant at steady-state levels, achieved within 4-5 days, resulted in an increase of 1.2-fold [90 % confidence interval (CI) 1.0-1.4], 1.4-fold (90 % CI 1.2-1.6), and 1.3-fold (90 % CI 1.2-1.4) in the maximum plasma concentration (C(max)), area under the concentration-time curve from time 0 to infinity (AUC(0-∞)), and terminal half-life (t(1/2)), respectively, of midazolam; the time to peak plasma concentration (t(max)) was unchanged. Whereas C(max) and t(max) were not influenced by almorexant, the AUC(0-∞) of hydroxy-midazolam increased by 1.2-fold (90 % CI 1.1-1.4) and the t(1/2) by 1.3-fold (90 % CI 1.0-1.5). Concomitant administration of simvastatin with almorexant at steady-state resulted in an increase of 2.7-fold (90 % CI 2.0-3.7) and 3.4-fold (90 % CI 2.6-4.4) in C(max) and AUC(0-∞), respectively, for simvastatin; the t(1/2) and t(max) were unchanged. The C(max) and AUC(0-∞) of hydroxyacid simvastatin both increased by 2.8-fold, with 90 % CIs of 2.3-3.5 and 2.2-3.5, respectively; the t(max) increased by 2 h and the t(1/2) was unchanged. The urinary 6-ß-hydroxycortisol/cortisol ratio was unaffected by almorexant. CONCLUSIONS: Our results suggest that the observed interaction was caused by the inhibition of CYP3A4 activity, most probably at the gut level.

Trust in science and belief in misinformation mediate the effects of political orientation on vaccine hesitancy and intention to be vaccinated.

In previous studies, anti-vaccination attitudes have been attributed either to far-right voters or to both far-left and far-right voters. The present study investigated the associations of political orientation with vaccine hesitancy and intention to be vaccinated against COVID-19, and the potential mediating roles of trust in science and belief in misinformation. A total of 750 Italian respondents completed an online questionnaire in the period between the second and the third wave of COVID-19 (from 9th March to 9th May 2021). The results showed that political orientation had both direct and indirect associations with vaccine hesitancy and vaccine intention, mediated by trust in science and belief in misinformation. Specifically, right-wing adherents were less trustful of scientists and believed in COVID-19-related misinformation more than left-wing adherents, and these two factors accounted for their higher vaccine hesitancy and reduced willingness to receive an anti-COVID-19 vaccination. Our findings are in line with the predictions of the mindsponge theory and suggest that communicative campaigns aimed at improving the rates of vaccine acceptance in right-wing adherents should be specifically focused on enhancing trust in science and reducing belief in misinformation.

Autobiographical memory in contact tracing: evidence from the COVID-19 pandemic.

Introduction: The recent COVID-19 pandemic has compelled various governments to trace all contacts of a confirmed case, as well as to identify the locations visited by infected individuals. This task, that requires the activation of our autobiographical memories, can make a difference in the spread of the contagion and was based primarily on telephone interviews with infected people. In this study, we examined whether participants were able to provide contact tracing information and whether their memories were influenced by salient events occurring during the initial phases of the pandemic. Methods: Participants were asked to fill in an online standardized form in which they recounted every day of the 2 weeks before, reporting as much information as possible. The time period selected included, among other things, the day on which the Italian government issued the decree initiating the COVID-19 lockdown. The task was completed twice, the first time relying solely on their memory, and the second time using external aids (diaries, mobile phones etc.). Reports were then coded using a scheme that segmented accounts into informational details, divided into two broad categories, internal and external. Results: Our findings showed that (i) the use of external aids was effective only when participants had to recall the day furthest away or if to-be-recalled events have low distinctiveness, and (ii) memories of internal details were recalled better than memories of external details. Participants were overall accurate and reported a large amount of information about people and places. However, because of the connection with key pandemic-related events, the effect was somewhat stronger on specific days (e.g., the day in which the lockdown was announced). Discussion: The results of this work could provide a useful tool for improving the design of contact tracing procedures in the event of an unwanted future public health crisis caused by a highly infectious agent.

Clinical Impact of COVID-19 on Multi-Drug-Resistant Gram-Negative Bacilli Bloodstream Infections in an Intensive Care Unit Setting: Two Pandemics Compared.

Two mutually related pandemics are ongoing worldwide: the COVID-19 and antimicrobial resistance pandemics. This study aims to evaluate the impact of COVID-19 on multi-drug-resistant Gram-negative bacteria (MDR-GN) bloodstream infections (BSIs) in a single intensive care unit (ICU). We conducted a retrospective study including patients admitted to the ICU, reorganized for COVID-19 patients' healthcare, with at least one confirmed MDR-GN BSI during 2019-2020. We compared clinical and microbiological features, incidence density, antibiotic therapy and mortality rate in pre- and during-COVID-19 pandemic periods. We estimated the impact of COVID-19 on mortality by means of univariate Cox regression analyses. A total of 46 patients were included in the study (28 non-COVID-19/18 COVID-19). Overall, 63 BSI episodes occurred (44/19), and non-COVID-19 patients had a higher incidence of MDR-GN BSIs and were more likely to present K. pneumoniae BSIs, while the COVID-19 group showed more A. baumannii BSIs with higher per pathogen incidence. COVID-19 patients presented more critical conditions at the BSI onset, a shorter hospitalization time from BSI to death and higher 30-day mortality rate from BSI onset. COVID-19 and septic shock were associated with 30-day mortality from MDR-GN BSIs, while early active therapy was a protective factor. In conclusion, COVID-19 showed a negative impact on patients with MDR-GN BSIs admitted to the ICU.

Pharmacokinetics and tolerability of almorexant in Japanese and Caucasian healthy male subjects.

BACKGROUND/AIMS: The aim of this study was to compare the pharmacokinetics and tolerability of single doses of the dual orexin receptor antagonist almorexant in Japanese and Caucasian healthy male subjects (n = 10 in each group, body weight matched ±5%). METHODS: Almorexant (200 mg) was administered in the morning in the fasted state. The pharmacokinetic parameters of almorexant were calculated by noncompartmental analysis from the plasma concentration data. RESULTS: The pharmacokinetics of almorexant in Japanese and Caucasian subjects were similar. The plasma concentration-time profile of almorexant was characterized by a rapid absorption and disposition. Peak plasma concentrations (C(max)) were reached at approximately 1.0 h in both ethnic groups. C(max) was 13% lower (ratio of geometric means [90% CI]: 0.87 [0.53, 1.43]), and the total exposure (AUC(0-)∞) was 15% lower (0.85 [0.54, 1.35]) in the Japanese subjects. There was no difference in the geometric mean ratio for t(1/2) between the two ethnic groups (1.03 [0.84, 1.25]). Almorexant was well tolerated in both ethnic groups. CONCLUSION: The pharmacokinetics and tolerability profiles of almorexant in Japanese and Caucasian healthy male subjects are similar. No dose adjustments for clinical studies with almorexant in Japanese subjects appear to be needed.

The Global Impact of the COVID-19 Pandemic on Individuals' and Couples' Sexuality.

The COVID-19 pandemic and its related restrictions significantly impacted individuals' health, wellbeing, and security. Isolation, limitation of movement, social distancing, and forced cohabiting have had a strong influence on all areas of people's lives as well as on their sexuality. Investigating how the COVID-19 outbreak and its consequences impacted people's sexuality was the primary aim of this review. Particularly, we focused on: (1) the variables associated with the improvement or the deterioration of individuals' and couples' lives during the pandemic; (2) the use of sex as a coping strategy; (3) the impact of COVID-19 outbreak on LGBT people. Results have shown that the worsening of sexual life seems to be related to couples' conflict, emotions and psychological difficulties, being female, being single or away from the partner, being a health care worker, and having children. Moreover, a detrimental effect on sexuality was associated with stress, forced cohabitation, routine, anxiety and worry about the job and the pandemic, feeling partner distance, being unhappy with their partner, and lack of privacy. On the other hand, improvements in sexuality were associated with living happily with a partner, being happy and satisfied with a partner, feeling less stressed and more bored, having more free time, having fewer recreation opportunities, and having minor workload. During the pandemic, there was an increase in using sex toys, pornography consumption, masturbating, and trying sexual experimentations. Among LGBT people, an increase was found in the number of casual sexual partners potentially due to the perceived lower likelihood of transmission through sex. Moreover, the increase in sexual activity may have represented a coping strategy to quarantine-related distress.

Depressive Symptoms among Individuals Hospitalized with COVID-19: Three-Month Follow-Up.

Individuals affected by Coronavirus Disease 2019 (COVID-19) may experience psychiatric symptoms, including depression and suicidal ideation, that could lead to chronic impairment and a reduction in quality of life. Specifically, depressive disorder shows high incidence and may lead to chronic impairment and a reduction in the quality of life. To date, no studies on the presence of suicidality and quantitative analysis of depressive symptoms and their risk factors have yet been published. In this study, we aim to assess the prevalence of depressive symptoms and related risk factors at 3 months after discharge to home care following hospitalization for COVID-19 infection. METHODS: Participants were contacted three months after hospital discharge from one of the five COVID-19 hospitals in Rome, as part of a larger project on health outcomes in COVID-19 inpatients (Long Term Neuropsychiatric Disorder in COVID-19 Project), and the Patient Health Questionnaire-9 (PHQ-9) was administered by telephone interview. RESULTS: Of 115 participants, 14.8% (N = 17) received a PHQ-9-based diagnosis of depression, and n = 7 of them scored 1 or more on the item on suicidality. A linear regression model showed the predictive role of female sex, pulmonary chronic condition and previous mental disorder in the development of depressive disorder; the latter was confirmed also by binary logistic regression. Severity indexes of disease (length of hospitalization and intensive care treatment) were found not to be associated with the development of depressive symptoms. CONCLUSIONS: A small but clinically meaningful number of participants in the current study reported that they experienced symptoms of depression and suicidal ideation 3 months post-discharge from their COVID-19 hospitalization. In particular, given the findings that a history of prior psychiatric disorders was predictive of the development of depression symptoms, clinicians should carefully monitor for the presence of all psychiatric symptoms at follow-up visits.

Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine.

Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling effects in humans. Insomnia is often associated with mental health problems, including depression. Hence, potential interactions with antidepressants deserve attention. Desipramine was selected as a model drug because it is mainly metabolized by CYP2D6, which is inhibited by almorexant in vitro. A single-center, randomized, placebo-controlled, two-way crossover study in 20 healthy male subjects was conducted to evaluate the pharmacokinetic and pharmacodynamic interactions between almorexant and desipramine. Almorexant 200mg or matching placebo (double-blind) was administered orally once daily in the morning for 10 days, and a single oral dose of 50mg desipramine (open-label) was administered on Day 5. Almorexant increased the exposure to desipramine 3.7-fold, suggesting that almorexant is a moderate inhibitor of desipramine metabolism through inhibition of CYP2D6. Conversely, desipramine showed no relevant effects on the pharmacokinetics of almorexant. Pharmacodynamic evaluations indicated that almorexant alone reduced visuomotor coordination, postural stability, and alertness, and slightly increased calmness. Desipramine induced a reduction in subjective alertness and an increase in pupil/iris ratio. Despite the increase in exposure to desipramine, almorexant and desipramine in combination showed the same pharmacodynamic profile as almorexant alone, except for prolonging reduced alertness and preventing the miotic effect of almorexant. Co-administration also prolonged the mydriatic effect of desipramine. Overall, repeated administration of almorexant alone or with single-dose desipramine was well tolerated. The lack of a relevant interaction with antidepressants, if confirmed for other DORAs, would be a key feature for a safer class of hypnotics.