The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study

Abstract Background: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. Aims: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. Results: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, Abstract Background: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. Aims: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. Results: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. Conclusions: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes

Nurses' attitudes in the interaction with patients who have beenexposed to sexual violenc : A literature review

Bakgrund Sexuellt våld förekommer dygnets alla timmar, världen över och är idag ett erkänt jämställdhetsproblem. Sexuellt våld är ett stigmatiserat område med olika attityder kring, på såväl individnivå som samhällsnivå. Vården utgör en central roll i att upptäcka och vårda personer som utsatts. Sjuksköterskan kan vara den första personen en som utsatts för sexuellt våld möter och detta möte kan vara avgörande för patientens välmående och återhämtning. Syftet Syftet var att belysa sjuksköterskors attityder i mötet med patienter som utsatts för sexuellt våld. Metod Litteraturöversikten genomfördes med induktiv ansats baserat på tio sammanställda artiklar; tre kvantitativa och sju kvalitativa från databaserna Cumulative Index to Nursing and Allied Health Literature Complete och Public Medline. Artiklarna sammanställdes med en modifierad tematisk innehållsanalys där resultatet diskuteras utifrån Madeleine Leininger Transkulturella omvårdnadsteori.  Resultat Resultatet presenteras utifrån tre huvudteman och två underkategorier i varje huvudtema. 1. Sjuksköterskors förutfattade meningar om den som utsatts för sexuellt våld, 2. Sjuksköterskors inställning till sin ansvarsroll i vårdandet av den som utsatts för sexuellt våld och 3. Organisatoriska och strukturella förutsättningar för sjuksköterskors synsätt gentemot den som utsatts för sexuellt våld. Sammanfattning Variationen av attityder hos sjuksköterskor i mötet med patienter som utsatts för sexuellt våld är stor. Flertalet sjuksköterskor uppfattar att patienter själva bär ansvar om förövaren ingår i bekantskapskretsen. Resultatet visar att sjuksköterskor i hög grad har förutfattade uppfattningar gentemot patienterna vilket resulterar i att sjuksköterskor bedömer och riktar tvivel gentemot patientens trovärdighet. Däremot lyfter flera sjuksköterskor vikten av att aldrig misstro, skuldbelägga eller döma patienten oavsett omständigheter. Flertalet sjuksköterskor uppfattar dessutom kunskapsmässiga och organisatoriska brister för att kunna vårda patienter som utsatts för sexuellt våld och ett bristande intresse att ta det vidare.Background Sexual violence occurs at all hours, all over the world. Sexual violence is an acknowledged cause of gender inequality. Sexual violence is a stigmatized area with various attitudes at both individual and societal levels. Healthcare plays a central role in identifying and caring for individuals who have been exposed to sexual violence. The nurse may be the first individual that a person who has been exposed to sexual violence meets. This interaction can be crucial for the victims well- being and recovery. Aim The aim was to describe nurses' attitudes in the interaction with patients who have been exposed to sexual violence. Method The literature review was conducted with an inductive approach based on ten articles; three quantitative and seven qualitative from the Cumulative Index to Nursing and Allied Health Literature Complete and Public Medline databases. The articles were compiled with a modified thematic content analysis, and the results are discussed based on Madeleine Leininger's Transcultural Nursing Theory. Results The results are presented based on three main themes and two subcategories in each main theme. 1. Nurses' preconceived notions about those who have been exposed to sexual violence, 2. Nurses' attitudes towards their responsibility in caring for those who have been exposed to sexual violence, and 3. Organizational and structural conditions for nurses' perspectives on those who have been exposed to sexual violence. Summary The variation in attitudes among nurses in the encounter with patients who have been exposed to sexual violence is significant. Most nurses perceive that patients themselves bear responsibility if the perpetrator is an acquaintance. The results show that nurses have preconceived notions about patients, resulting in nurses assessing and doubting the patient's credibility. However, several nurses emphasize the importance of never distrusting, blaming, or judging the patient regardless of circumstances. Moreover, most nurses perceive a lack of knowledge and organizational gaps in caring for patients who have been exposed to sexual violence and a lack of interest in pursuing it further

Nurses' attitudes in the interaction with patients who have beenexposed to sexual violenc : A literature review

Bakgrund Sexuellt våld förekommer dygnets alla timmar, världen över och är idag ett erkänt jämställdhetsproblem. Sexuellt våld är ett stigmatiserat område med olika attityder kring, på såväl individnivå som samhällsnivå. Vården utgör en central roll i att upptäcka och vårda personer som utsatts. Sjuksköterskan kan vara den första personen en som utsatts för sexuellt våld möter och detta möte kan vara avgörande för patientens välmående och återhämtning. Syftet Syftet var att belysa sjuksköterskors attityder i mötet med patienter som utsatts för sexuellt våld. Metod Litteraturöversikten genomfördes med induktiv ansats baserat på tio sammanställda artiklar; tre kvantitativa och sju kvalitativa från databaserna Cumulative Index to Nursing and Allied Health Literature Complete och Public Medline. Artiklarna sammanställdes med en modifierad tematisk innehållsanalys där resultatet diskuteras utifrån Madeleine Leininger Transkulturella omvårdnadsteori.  Resultat Resultatet presenteras utifrån tre huvudteman och två underkategorier i varje huvudtema. 1. Sjuksköterskors förutfattade meningar om den som utsatts för sexuellt våld, 2. Sjuksköterskors inställning till sin ansvarsroll i vårdandet av den som utsatts för sexuellt våld och 3. Organisatoriska och strukturella förutsättningar för sjuksköterskors synsätt gentemot den som utsatts för sexuellt våld. Sammanfattning Variationen av attityder hos sjuksköterskor i mötet med patienter som utsatts för sexuellt våld är stor. Flertalet sjuksköterskor uppfattar att patienter själva bär ansvar om förövaren ingår i bekantskapskretsen. Resultatet visar att sjuksköterskor i hög grad har förutfattade uppfattningar gentemot patienterna vilket resulterar i att sjuksköterskor bedömer och riktar tvivel gentemot patientens trovärdighet. Däremot lyfter flera sjuksköterskor vikten av att aldrig misstro, skuldbelägga eller döma patienten oavsett omständigheter. Flertalet sjuksköterskor uppfattar dessutom kunskapsmässiga och organisatoriska brister för att kunna vårda patienter som utsatts för sexuellt våld och ett bristande intresse att ta det vidare.Background Sexual violence occurs at all hours, all over the world. Sexual violence is an acknowledged cause of gender inequality. Sexual violence is a stigmatized area with various attitudes at both individual and societal levels. Healthcare plays a central role in identifying and caring for individuals who have been exposed to sexual violence. The nurse may be the first individual that a person who has been exposed to sexual violence meets. This interaction can be crucial for the victims well- being and recovery. Aim The aim was to describe nurses' attitudes in the interaction with patients who have been exposed to sexual violence. Method The literature review was conducted with an inductive approach based on ten articles; three quantitative and seven qualitative from the Cumulative Index to Nursing and Allied Health Literature Complete and Public Medline databases. The articles were compiled with a modified thematic content analysis, and the results are discussed based on Madeleine Leininger's Transcultural Nursing Theory. Results The results are presented based on three main themes and two subcategories in each main theme. 1. Nurses' preconceived notions about those who have been exposed to sexual violence, 2. Nurses' attitudes towards their responsibility in caring for those who have been exposed to sexual violence, and 3. Organizational and structural conditions for nurses' perspectives on those who have been exposed to sexual violence. Summary The variation in attitudes among nurses in the encounter with patients who have been exposed to sexual violence is significant. Most nurses perceive that patients themselves bear responsibility if the perpetrator is an acquaintance. The results show that nurses have preconceived notions about patients, resulting in nurses assessing and doubting the patient's credibility. However, several nurses emphasize the importance of never distrusting, blaming, or judging the patient regardless of circumstances. Moreover, most nurses perceive a lack of knowledge and organizational gaps in caring for patients who have been exposed to sexual violence and a lack of interest in pursuing it further

Onset and Severity of Early Disruptive Behavioral Disorders in Treatment-Seeking Substance Use Disorder Patients with and without Attention-Deficit/Hyperactivity Disorder

This study addressed the age of onset of conduct disorder (CD) and oppositional defiant disorder (ODD) in treatment-seeking substance use disorder (SUD) patients with and without adult attention-deficit/hyperactivity disorder (ADHD) and its association with early onset of SUD. Methods: We examined data from the 2nd International ADHD in Substance Use Disorders Prevalence Study, including 400 adults in SUD treatment from Puerto Rico, Hungary, and Australia. ADHD, SUD, and CD/ODD were assessed with the Conners Adult ADHD Diagnostic Interview for DSM-IV, the MINI International Neuropsychiatric Interview, and the K-SADS, respectively. Cox regression analyses modeled time to emergence of CD/ODD separately for SUD patients with and without adult ADHD. Linear regression models examined associations between age of onset of SUD and presence of ADHD and adjusted for sex, age, and country. To assess the mediating role of CD/ODD on the association of ADHD with onset of SUD, adjusted regression models were estimated. Results: Treatment-seeking SUD patients with ADHD presented an earlier onset of CD/ODD compared with those without ADHD. CD/ODD symptom loads were higher among the SUD and ADHD group. Age of first substance use and SUD were significantly earlier in SUD patients with ADHD, and these findings remained significant after adjustment for demographics and coexisting CD/ODD. Conclusions: ADHD is associated with earlier onset of SUD as well as with an earlier onset of more frequent and more severe disruptive behavioral disorders. These findings may inform preventive interventions to mitigate adverse consequences of ADHD

Onset and severity of early sisruptive eehavioral disorders in treatment-seeking substance use disorder patients with and without attention-deficit/hyperactivity disorder

$\bf Aims:$ This study addressed the age of onset of conduct disorder (CD) and oppositional defiant disorder (ODD) in treatment-seeking substance use disorder (SUD) patients with and without adult attention-deficit/hyperactivity disorder (ADHD) and its association with early onset of SUD. $\bf Methods:$ We examined data from the 2nd $\textit {International ADHD in Substance Use Disorders Prevalence Study}$, including 400 adults in SUD treatment from Puerto Rico, Hungary, and Australia. ADHD, SUD, and CD/ODD were assessed with the $\textit {Conners Adult ADHD Diagnostic Interview for DSM-IV}$, the $\textit {MINI International Neuropsychiatric Interview}$, and the K-SADS, respectively. Cox regression analyses modeled time to emergence of CD/ODD separately for SUD patients with and without adult ADHD. Linear regression models examined associations between age of onset of SUD and presence of ADHD and adjusted for sex, age, and country. To assess the mediating role of CD/ODD on the association of ADHD with onset of SUD, adjusted regression models were estimated. $\bf Results:$ Treatment-seeking SUD patients with ADHD presented an earlier onset of CD/ODD compared with those without ADHD. CD/ODD symptom loads were higher among the SUD and ADHD group. Age of first substance use and SUD were significantly earlier in SUD patients with ADHD, and these findings remained significant after adjustment for demographics and coexisting CD/ODD. $\bf Conclusions:$ ADHD is associated with earlier onset of SUD as well as with an earlier onset of more frequent and more severe disruptive behavioral disorders. These findings may inform preventive interventions to mitigate adverse consequences of ADHD

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants

Abstract As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Acknowledgements: We thank all the participants in this trial; the members of the safety monitoring committee (K. Talaat, J. Treanor, G. Paulsen and D. Stablein), who provided thoughtful discussions resulting in the early trial design; and staff members at Moderna, Pfizer and Sanofi–GSK for their collaboration, scientific input and sharing of documents needed to implement the trial. The COVAIL trial has been funded in part with federal funds from the NIAID and the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order no. 75N91022F00007, and in part by the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Government Contract no. 75A50122C00008 with Monogram Biosciences, LabCorp. This work was also supported in part with federal funds from the NIAID, NIH, under contract no. 75N93021C00012, and by the Infectious Diseases Clinical Research Consortium (IDCRC) through the NIAID, under award no. UM1AI148684. D.J.S., A.N., S.H.W. and S.T. were supported by the NIH—NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract no. 75N93021C00014 as part of the SAVE program. D.C.M. and A.E. were supported by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) contract no. 75N93019C00050. Testing of neutralizing antibody titers by Monogram Biosciences, LabCorp has been funded in part with federal funds from the Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract no. 75A50122C00008. Testing for anti-N-specific antibody was conducted by Cerba Research under contract no. 75N93021D00021. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NIH—NIAID.Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037