Epidemiology and clinical manifestations of different enterovirus and rhinovirus types show that EV-D68 may still have an impact on severity of respiratory infections.

Respiratory infections are often caused by enteroviruses (EVs). The aim of this study was to identify whether certain types of EV were more likely to cause severe illness in 2016, when an increasing spread of upper respiratory infections was observed in Gothenburg, Sweden. The EV strain in 137 of 1341 nasopharyngeal samples reactive for EV by polymerase chain reaction could be typed by sequencing the viral 5'-untranslated region and VP1 regions. Phylogenetic trees were constructed. Patient records were reviewed. Hospital care was needed for 46 of 74 patients with available medical records. The majority of the patients (83) were infected with the rhinovirus (RV). The remaining 54 were infected with EV A, B, C, and D strains of 13 different types, with EV-D68 and CV-A10 being the most common (17 vs. 14). Significantly more patients with EV-D68 presented with dyspnea, both when compared with other EV types (p = 0.003) and compared to all other EV and RV infections (p = 0.04). Phylogenetic analysis of the sequences revealed the spread of both Asian and European CV-A10 strains and 12 different RV C types. This study showed an abundance of different EV types spreading during a year with increased upper respiratory increased infections. EV-D68 infections were associated with more severe disease manifestation. Other EV and RV types were more evenly distributed between hospitalized and nonhospitalized patients. The EV type CV-A10 was also found in infected patients, which warrants further studies and surveillance, as this pathogen could cause more severe disease and outbreaks of hand, foot, and mouth disease.

Implementing and Sustaining SHARE: An Exposure-Based Psychotherapy Group for Incarcerated Women Survivors of Sexual Violence.

Although incarcerated women are a highly victimized population, therapy for sexual violence victimization (SVV) sequela is not routinely offered in prison. SHARE is a group therapy for SVV survivors that was successfully implemented and sustained in a women's correction center. Here, we aimed to identify implementation factors and strategies that led to SHARE's success and describe incarcerated women's perspectives on the program. We conducted a retrospective process evaluation using interviews structured according to EPIS, a well-established implementation science framework. Participants (N = 22) were incarcerated women, members of the SHARE treatment team, and members of the correction center's leadership, therapeutic team, and volunteer program. Factors that facilitated SHARE implementation varied by EPIS phase and organization. Positive inter-organizational and interpersonal relationships were key across phases, as were the synergies between both the strengths and needs of each organization involved in implementation. Incarcerated women reported a strong need for SHARE and did not report any concerns about receiving trauma therapy in a carceral setting. Therapy for SVV sequelae, including exposure-based therapy, is possible to implement and sustain in carceral settings. Community-academic partnerships may be a particularly feasible way to expand access to SVV therapy for incarcerated women.

Interpersonal vs. Non-Interpersonal Cumulative Traumas and Psychiatric Symptoms in Treatment-Seeking Incarcerated Women.

Incarcerated women are at elevated risk of lifetime trauma exposure. Prevalence rates of trauma exposure and how these events relate to specific domains of psychiatric symptomology among this group are lacking. This study hypothesized a greater range of diverse cumulative trauma experiences (CTEs) would be positively associated with psychiatric symptoms in general (depression, PTSD, distress tolerance), but that interpersonal CTEs in particular would be uniquely associated with greater symptoms of guilt and shame. A total of 112 women (87% White, Mage = 34 years) seeking treatment for a history of sexual violence victimization participated in the study. Women incarcerated for nonviolent offenses at two minimum-security prisons completed self-report measures of exposure to diverse traumatic events and internalizing symptoms. On average, participants reported a history of experiencing 5.46 traumatic event types. Total CTEs was significantly associated with all psychiatric variables in the expected direction. While both interpersonal and non-interpersonal CTEs were positively associated with levels of PTSD, depression, and distress intolerance, only interpersonal CTEs were significantly associated with guilt and shame. Traumatic experiences that are interpersonal in nature may confer specific risk for psychiatric symptoms in victims.

Hepatitis E virus genotype 3 is associated with gallstone-related disease.

Objective: Hepatitis E virus (HEV) genotype 3 is endemic in Northern Europe and despite a high seroprevalence of anti-HEV IgG antibodies among blood donors (≈17%), few clinical cases are notified in Sweden. Low awareness of hepatitis E and its possible symptoms may contribute to this discrepancy. The aim of this study was to investigate the prevalence of acute HEV infection among hospital admitted patients with abdominal pain and elevated liver enzymes.Materials and methods: During 2016-2017, 148 adult patients with serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > twice normal levels were prospectively enrolled at surgical wards at three Swedish hospitals. Serum samples were analyzed for HEV RNA as well as anti-HEV IgM and IgG, and medical records were reviewed.Results: Six (6/148, 4.1%) patients were HEV infected confirmed by detectable HEV RNA, but only one of these patients had detectable anti-HEV antibodies. Four of the HEV infected patients were diagnosed with gallstone-related disease: three with biliary pancreatitis and one with biliary colic. The remaining two were diagnosed with bowel obstruction and pancreatic malignancy. Four HEV strains were typed by sequencing to genotype 3.Conclusions: This study identified acute HEV3 infection in 4% of the patients with elevated liver enzymes admitted to a surgical ward. HEV infection was not the solitary disease leading to hospitalization, instead it was found to be associated with other surgical conditions such as gallstone-related disease including biliary pancreatitis. Additionally, HEV RNA might be the preferential diagnostic tool for detecting ongoing HEV infection.

Diagnostic Performance of Five Assays for Anti-Hepatitis E Virus IgG and IgM in a Large Cohort Study.

Determination of anti-hepatitis E virus (anti-HEV) antibodies is still enigmatic. There is no gold standard, and results obtained with different assays often diverge. Herein, five assays were compared for detection of anti-HEV IgM and IgG. Serum samples from 500 Swedish blood donors and 316 patients, of whom 136 had suspected HEV infection, were analyzed. Concordant results for IgM and IgG with all assays were obtained only for 71% and 70% of patients with suspected hepatitis E, respectively. The range of sensitivity for anti-HEV detection was broad (42% to 96%); this was reflected in the detection limit, which varied up to 19-fold for IgM and 17-fold for IgG between assays. HEV RNA was analyzed in all patients and in those blood donors reactive for anti-HEV in any assay, and it was found in 26 individuals. Among all of the assays, both anti-HEV IgG and IgM were detected in 10 of those individuals. Twelve had only IgG and, in 7 of those 12, IgG was only detected with the two most sensitive assays. Three of the HEV-RNA-positive samples were negative for anti-HEV IgM and IgG in all assays. With the two most sensitive assays, anti-HEV IgG was identified in 16% of the blood donor samples and in 66% of patients with suspected HEV infection. Because several HEV-RNA-positive samples had only anti-HEV IgG without anti-HEV IgM or lacked anti-HEV antibodies, analysis for HEV RNA may be warranted as a complement in the laboratory diagnosis of ongoing HEV infection.

Critical role for hyperpolarization-activated cyclic nucleotide-gated channel 2 in the AIF-mediated apoptosis.

Cellular calcium uptake is a controlled physiological process mediated by multiple ion channels. The exposure of cells to either one of the protein kinase C (PKC) inhibitors, staurosporine (STS) or PKC412, can trigger Ca²(+) influx leading to cell death. The precise molecular mechanisms regulating these events remain elusive. In this study, we report that the PKC inhibitors induce a prolonged Ca²(+) import through hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) in lung carcinoma cells and in primary culture of cortical neurons, sufficient to trigger apoptosis-inducing factor (AIF)-mediated apoptosis. Downregulation of HCN2 prevented the drug-induced Ca²(+) increase and subsequent apoptosis. Importantly, the PKC inhibitors did not cause Ca²(+) entry into HEK293 cells, which do not express the HCN channels. However, introduction of HCN2 sensitized them to STS/PKC412-induced apoptosis. Mutagenesis of putative PKC phosphorylation sites within the C-terminal domain of HCN2 revealed that dephosphorylation of Thr549 was critical for the prolonged Ca²(+) entry required for AIF-mediated apoptosis. Our findings demonstrate a novel role for the HCN2 channel by providing evidence that it can act as an upstream regulator of cell death triggered by PKC inhibitors.

The antibacterial effect of nitric oxide against ESBL-producing uropathogenic E. coli is improved by combination with miconazole and polymyxin B nonapeptide.

BACKGROUND: Nitric oxide (NO) is produced as part of the host immune response to bacterial infections, including urinary tract infections. The enzyme flavohemoglobin, coded by the hmp gene, is involved in protecting bacterial cells from the toxic effects of NO and represents a potentially interesting target for development of novel treatment concepts against resistant uropathogenic bacteria. The aim of the present study was to investigate if the in vitro antibacterial effects of NO can be enhanced by pharmacological modulation of the enzyme flavohemoglobin. RESULTS: Four clinical isolates of multidrug-resistant extended-spectrum ß-lactamase (ESBL)-producing uropathogenic E. coli were included in the study. It was shown that the NO-donor substance DETA/NO, but not inactivated DETA/NO, caused an initial growth inhibition with regrowth noted after 8 h of exposure. An hmp-deficient strain showed a prolonged growth inhibition in response to DETA/NO compared to the wild type. The imidazole antibiotic miconazole, that has been shown to inhibit bacterial flavohemoglobin activity, prolonged the DETA/NO-evoked growth inhibition. When miconazole was combined with polymyxin B nonapeptide (PMBN), in order to increase the bacterial wall permeability, DETA/NO caused a prolonged bacteriostatic response that lasted for up to 24 h. CONCLUSION: An NO-donor in combination with miconazole and PMBN showed enhanced antimicrobial effects and proved effective against multidrug-resistant ESBL-producing uropathogenic E. coli.

Sexual violence therapy group in a women's correctional facility: a preliminary evaluation.

This pilot study was an evaluation of an 8-week exposure-based therapy group targeting sexual trauma in incarcerated women, an underserved population with high rates of trauma exposure. Preliminary findings from 14 female prisoners showed significant decreases in depressive and anxiety symptoms from pre- to posttreatment. Of the women who were above the screening cutoff for possible posttraumatic stress disorder (PTSD; n = 13), depression (n = 12), and generalized anxiety disorder (GAD; n = 12) at pretreatment, approximately 60% had recovered, meaning they had symptom reductions that placed them below the cutoff at posttreatment (n = 8 for PTSD; n = 8 for depression, and n = 9 for GAD). In addition, 85% of participants reported a clinically significant reduction in depressive symptoms and 50% in GAD symptoms. The findings show promise for successful group treatment of sexual violence sequelae in incarcerated women.

To SHARE or not to SHARE: Exploring incarcerated women's decisions about enrolling in exposure-based group therapy.

Exposure therapies effectively treat traumatic stress sequelae, including that which follows sexual violence victimization (SVV). Carceral facilities house women with significantly higher rates of SVV than community samples, yet they rarely implement this form of treatment. In this study, women with histories of SVV (n = 63) completed semistructured qualitative interviews about their decision to enroll or not enroll in an exposure-based group therapy called Survivors Healing from Abuse: Recovery through Exposure while incarcerated. All study participants were previously incarcerated in a prison, where they were offered the opportunity to enroll in Survivors Healing from Abuse: Recovery through Exposure. We used the theory of planned behavior to analyze factors that affected enrollment decisions. Results revealed that enrollment decisions among incarcerated women can be categorized within the theory of planned behavior framework. Interview responses indicated that recognizing current problems as related to experiences of SVV, holding positive attitudes about mental health treatment, observing peers engaging in help-seeking behaviors, and perceiving treatment as accessible were linked with enrollment. Negative perceptions of treatment, fear of judgment, and negative peer influence (e.g., distrust of peers) were linked to decisions not to enroll. While certain beliefs were influenced by contextual features of incarceration (e.g., peer interactions outside of group therapy), many overlapped with factors found to influence help-seeking among nonincarcerated populations. Findings have implications for how to engage members of underserved populations in resource-deprived contexts who have a great need for treatment of traumatic symptoms secondary to sexual violence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Quantitative target engagement of RIPK1 in human whole blood via the cellular thermal shift assay for potential pre-clinical and clinical applications.

The cellular thermal shift assay (CETSA®) is a target engagement method widely used for preclinical characterization of small molecule compounds. CETSA® has been used for semi-quantitative readouts in whole blood with PBMC isolation, and quantitative, plate-based readouts using cell lines. However, there has been no quantitative evaluation of CETSA® in unprocessed human whole blood, which is preferred for clinical applications. Here we report two separate assay formats - Alpha CETSA® and MSD CETSA® - that require less than 100 µL of whole blood per sample without PBMC isolation. We chose RIPK1 as a proof-of-concept target and, by measuring engagement of seven different inhibitors, demonstrate high assay sensitivity and robustness. These quantitative CETSA® platforms enable possible applications in preclinical pharmacokinetic-pharmacodynamic studies, and direct target engagement with small molecules in clinical trials.

Activation of NF-κB protein prevents the transition from juvenile ovary to testis and promotes ovarian development in zebrafish.

Testis differentiation in zebrafish involves juvenile ovary to testis transformation initiated by an apoptotic wave. The molecular regulation of this transformation process is not fully understood. NF-κB is activated at an early stage of development and has been shown to interact with steroidogenic factor-1 in mammals, leading to the suppression of anti-Müllerian hormone (Amh) gene expression. Because steroidogenic factor-1 and Amh are important for proper testis development, NF-κB-mediated induction of anti-apoptotic genes could, therefore, also play a role in zebrafish gonad differentiation. The aim of this study was to examine the potential role of NF-κB in zebrafish gonad differentiation. Exposure of juvenile zebrafish to heat-killed Escherichia coli activated the NF-κB pathways and resulted in an increased ratio of females from 30 to 85%. Microarray and quantitative real-time-PCR analysis of gonads showed elevated expression of NF-κB-regulated genes. To confirm the involvement of NF-κB-induced anti-apoptotic effects, zebrafish were treated with sodium deoxycholate, a known inducer of NF-κB or NF-κB activation inhibitor (NAI). Sodium deoxycholate treatment mimicked the effect of heat-killed bacteria and resulted in an increased proportion of females from 25 to 45%, whereas the inhibition of NF-κB using NAI resulted in a decrease in females from 45 to 20%. This study provides proof for an essential role of NF-κB in gonadal differentiation of zebrafish and represents an important step toward the complete understanding of the complicated process of sex differentiation in this species and possibly other cyprinid teleosts as well.

Na,K-ATPase signal transduction triggers CREB activation and dendritic growth.

Dendritic growth is pivotal in the neurogenesis of cortical neurons. The sodium pump, or Na,K-ATPase, is an evolutionarily conserved protein that, in addition to its central role in establishing the electrochemical gradient, has recently been reported to function as a receptor and signaling mediator. Although a large body of evidence points toward a dual function for the Na,K-ATPase, few biological implications of this signaling pathway have been described. Here we report that Na,K-ATPase signal transduction triggers dendritic growth as well as a transcriptional program dependent on cAMP response element binding protein (CREB) and cAMP response element (CRE)-mediated gene expression, primarily regulated via Ca(2+)/calmodulin-dependent protein (CaM) kinases. The signaling cascade mediating dendritic arbor growth also involves intracellular Ca(2+) oscillations and sustained phosphorylation of mitogen-activated protein (MAP) kinases. Thus, our results suggest a novel role for the Na,K-ATPase as a modulator of dendritic growth in developing neurons.

Decreases in psychiatric symptoms persist following exposure-based group therapy for sexual violence victimization among incarcerated women.

Survivors Healing from Abuse: Recovery through Exposure (SHARE) is a brief, exposure-based group treatment for incarcerated female survivors of sexual violence. Preliminary evaluations of SHARE showed declines in depression and posttraumatic stress disorder (PTSD) symptoms from pre- to posttreatment. However, prior investigations have not included a longitudinal follow-up period and thus knowledge of whether therapeutic benefits persist following the termination of the group is lacking. Here, we examined data from 57 incarcerated women who completed SHARE and provided follow-up data while still incarcerated (M = 95 days posttreatment). Results from a one-way repeated-measures ANOVA showed significant reductions in PTSD and depression symptoms from pre- to posttreatment (large effect sizes), with symptoms further reduced during the follow-up period. In addition, McNemar tests showed a significant reduction in the proportion of participants at or above the clinical cut-off for probable PTSD and depression from pre- to posttreatment as well as from posttreatment to the follow-up assessment. Together, results suggest that the therapeutic benefits of SHARE persist after treatment is completed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Does Group Size Matter? Group Size and Symptom Reduction Among Incarcerated Women Receiving Psychotherapy Following Sexual Violence Victimization.

Survivors Healing from Abuse: Recovery through Exposure (SHARE) is an eight-week therapy group for incarcerated women who have experienced sexual violence victimization. SHARE requires each member to complete an imaginal exposure and to listen when others share their experiences of victimization. While trauma-focused group interventions including SHARE are associated with reductions in internalizing symptoms, little work has examined how group characteristics predict symptom decreases. The purpose of this study was to examine whether group size was associated with symptom changes pre- to post-treatment. Participants (n=140 across 29 groups) completed self-report measures of posttraumatic stress symptoms before and after completing SHARE. Multilevel modeling revealed the majority of the variance in post-treatment symptoms was attributed to individual factors rather than group factors. Symptom change was comparable for groups of two to eight women; declines in symptom improvement were observed at a group size of ten participants.

"I'm not alone, my story matters": Incarcerated women's perspectives on the impact and acceptability of group psychotherapy involving imaginal exposure to sexual assault memories.

BACKGROUND: Although it is clear that incarcerated women need access to effective therapies for trauma sequelae, some have argued that one of the most effective treatments - exposure therapy - should not be provided in carceral settings due to the presumed lack of safety and stability making such an intervention inappropriate. Group therapy, the typical mode of intervention in prisons, has also been presumed to be unacceptable for exposure-based processing due to assumptions that hearing others' trauma narratives would be traumatizing and unhelpful to listeners. However, there is a lack of data to support either of the aforementioned assumptions. This study examined the acceptability of an exposure-based group therapy for women survivors of sexual violence who were currently incarcerated (N = 61) by asking women themselves about their experiences completing an exposure-based group therapy protocol (SHARE; Survivors Healing from Abuse: Recovery through Exposure) while incarcerated. We assessed women's reasons for enrolling in the group, satisfaction with various therapy components (e.g., exposure, skill-building) and the treatment overall, and experiences of both sharing and listening to trauma narratives using a feedback survey that included a mix of multiple-choice and open-ended questions. Treatment dropout was examined as an additional index of acceptability. RESULTS: Treatment completion was very high (88.8%). Nearly all women who completed the group reported that they would recommend it to other incarcerated women (96.7%, with the remaining 3.3% reporting "it depends"). Qualitative results revealed overwhelmingly positive feedback about the effect of the group and indicated that sharing and listening to trauma narratives in a group setting serve discrete but dually important functions. Specifically, women almost universally experienced listening to others' trauma narratives (i.e., exposures) in the SHARE group context as helpful-making them feel less alone and normalizing their experiences. Sharing one's own story primarily provided an emotional release and/or transformation (i.e., an intrapersonal rather than interpersonal function). CONCLUSIONS: Our findings challenge common concerns about the appropriateness of 1) prison as a context for trauma-focused treatments, including exposure and 2) sharing trauma narratives in a group setting. Unless empirical evidence demonstrating harm is uncovered, best practices for PTSD and other trauma-related sequelae-those recommended in reputable treatment guidelines and interventions like SHARE that incorporate components shown to be effective (e.g., cognitive challenging, exposure)-should be offered to incarcerated women as part of standard of care.

Clinical fMRI of language function in aphasic patients: reading paradigm successful, while word generation paradigm fails.

BACKGROUND: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. PURPOSE: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. MATERIAL AND METHODS: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. RESULTS: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. CONCLUSION: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

Sexual Victimization and Mental Illness Prevalence Rates Among Incarcerated Women: A Literature Review.

Incarcerated women evidence high rates of both interpersonal trauma and mental illness. In particular, the rates of sexual violence victimization are so high that some researchers have suggested that sexual abuse may be a pathway to prison for women, likely through the development of mental illness, including substance abuse. This review article summarizes the literature on sexual victimization (n = 32 articles; 28 independent studies) and mental illness (n = 11 articles; 8 independent studies) prevalence among samples of incarcerated women (Ns ≥ 100) in context of methodological choices within included articles. Best estimates for sexual victimization from studies using established survey methods were as follows: 50-66% for child sexual abuse, 28-68% for adult sexual abuse, and 56-82% for lifetime sexual assault. Although data directly comparing prevalence of sexual victimization among incarcerated women to prevalence for other groups are limited, the existing data indicate that incarcerated women have significantly greater exposure than incarcerated men and community samples of women. Moreover, compared to findings from the National Comorbidity Survey-Replication, incarcerated women evidence greater prevalence of most lifetime and current mental illnesses, especially depressive disorders, post-traumatic stress disorder, and substance use disorders. Surprisingly, only two independent studies have investigated the overlap between sexual victimization and mental illness in samples of incarcerated women. Both studies found disproportionally high rates of mental illness among victims of sexual violence. Suggestions and implications for research, policy, and practice are discussed.

Replicating outcomes of Survivors Healing from Abuse: Recovery through Exposure (SHARE): A brief exposure-based group treatment for incarcerated survivors of sexual violence.

OBJECTIVE: Survivors Healing from Abuse: Recovery through Exposure (SHARE) is a group treatment for incarcerated women that targets sexual abuse sequelae. Previous research on SHARE found significant reductions in posttraumatic stress disorder (PTSD), depression, and generalized anxiety disorder (GAD) symptoms among completers. However, evidence for SHARE has been limited to open pilot studies conducted in one prison. Therefore, this study sought to replicate the results of previous SHARE studies in a separate facility. METHOD: Thirty-two women incarcerated in a minimum-security prison participated in an open trial of SHARE. Six separate groups were conducted, each consisting of eight 1.5-hr sessions. RESULTS: Pre- to posttreatment symptom reductions in PTSD, depression, and GAD were statistically significant with large effect sizes. Moreover, 21-37% of treatment completers evidenced reliable change in their symptom reduction during the course of treatment. Most women who did not evidence reliable change were already below the clinical cutoff on the corresponding symptom measure at pre-treatment and remained below by post-treatment. CONCLUSIONS: These results are consistent with prior studies of SHARE and provide additional support for the positive outcomes of this brief, targeted trauma-focused treatment for incarcerated women. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

TOB-STOP-COP (TOBacco STOP in COPd trial): study protocol-a randomized open-label, superiority, multicenter, two-arm intervention study of the effect of "high-intensity" vs. "low-intensity" smoking cessation intervention in active smokers with chronic obstructive pulmonary disease.

BACKGROUND: Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and it contributes to the development of many other serious diseases. Smoking cessation in COPD patients is known to improve survival and reduce the number of hospitalization-requiring acute exacerbations of COPD. However, smoking cessation interventions in these patients have only been successful for approximately 15-20% for consistent smoking abstinence in 12 months. Thus, more effective interventions are needed for this patient group. The aim of this study is to determine whether a high-intensity intervention compared to a low-intensity intervention can increase the proportion of persistent (> 12 months) anamnestic and biochemical smoking cessation in active smokers with COPD. METHODS: This study is a randomized controlled trial. A total of 600 active smokers with COPD will be randomly assigned 1:1 to either a standard treatment (guideline-based municipal smoking cessation program, "low intensity" group) or an intervention ("high-intensity" group) group, which consists of group sessions, telephone consultations, behavior design, hotline, and "buddy-matching" (smoker matched with COPD patient who has ceased smoking). Both groups will receive pharmacological smoking cessation. The primary endpoint is anamnestic and biochemical (cotinine analysis in urine) validated smoking cessation after 12 months. DISCUSSION: The potential benefit of this project is to improve smoking cessation rates and thereby reduce smoking-related exacerbations of COPD. In addition, the project can potentially benefit from increasing the quality of life and longevity of COPD patients and reducing the risk of other smoking-related diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT04088942 . Registered on 13 September 2019.