UNASSIGNED: It is difficult to recognize vitamin B12 deficiency and to evaluate the effect of B12 treatment due to a broad range of variable clinical symptoms overlapping with other diseases and diagnostic biomarkers that quickly normalize during treatment. This poses a risk of delay in diagnosis and a challenge to uniformly monitor the effect of B12 treatment. There is a need for a new clinical outcome measure suitable for clinical practice and clinical evaluation studies.
UNASSIGNED: To develop a Patient-Reported Outcome Measure (PROM) which measures the severity of vitamin B12 deficiency symptoms.
UNASSIGNED: The B12 PROM was developed by (1) gathering input from experts and literature review to define a construct and develop a conceptual model, (2) processing input from health care providers, scientists, and patients to develop items and response options, and (3) improving items based on the feedback from laypersons, test interviews, semi-structured cognitive interviews with patients, and forward and backward translation (ENG-NL).
UNASSIGNED: The B12 PROM includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Cognitive interviews demonstrated good comprehensibility and comprehensiveness.
UNASSIGNED: This study is the first step in the development of a disease-specific PROM for vitamin B12 deficiency to measure the burden of symptoms. Further validation and reliability testing are necessary before the PROM can be applied in clinical practice and research.
Plain language titleDevelopment of a Vitamin B12 Deficiency Questionnaire for Clinical Practice and ResearchPlain language summaryThis study is the first step in the development of a questionnaire for vitamin B12 deficiency to measure the severity of vitamin B12 deficiency symptoms. The questionnaire includes 62 items grouped into 8 categories of symptoms related to vitamin B12 deficiency (General, Senses, Thinking, In limbs and/or face, Movement, Emotions, Mouth & Abdomen, Urinary tract & Reproductive organs). Interviews with patients demonstrated good comprehensibility and comprehensiveness of the questionnaire. Further testing is necessary before the questionnaire can be applied in clinical practice and research.

OBJECTIVE: Prostate cancer is one of the most common malignant neoplasms in elderly males, with radical prostatectomy being the established therapeutic approach for localized disease. Patients undergoing this surgical procedure frequently experience increased negative emotions and symptomatology during the perioperative period, likely due to concerns about the illness and its treatment. The present study aims to investigate the effects of a novel educational approach involving a whole-process visualization and collaborative nursing discussions on perioperative symptoms and emotional well-being in radical prostatectomy patients.
METHODS: Data were prospectively collected from 310 patients admitted to the hospital between June 2021 and December 2023, all of whom were scheduled to undergo radical prostatectomy. These patients were randomly assigned to either the intervention group (receiving new model education) or the control group (receiving conventional education), with 155 patients in each group. The study compared basic demographic information, anxiety and depression scores, fear of disease progression scores, quality-of-life scores, main symptom scores, and changes in perioperative vital signs between the two groups.
RESULTS: No statistically significant differences were observed between the two groups in terms of age, comorbidities, insurance type, education level, income, and tumor history (P > 0.05). Similarly, there were no significant differences in anxiety and depression scores, proportion of patients with anxiety and depression, vital signs, and fear of disease progression scores between the two groups at Time 1 stage (P > 0.05). During stages Time 2 and Time 3, the intervention group exhibited lower anxiety and depression scores, a lower proportion of anxious and depressed patients, as well as significantly reduced blood pressure and heart rate fluctuations compared to the control group (P < 0.05). Following radical prostatectomy, the main symptoms of patients, such as pain, nausea, and fatigue, were assessed using the MADIS Symptom Assessment Scale on days 1-3 post-surgery. The intervention group exhibited significantly lower scores for three symptoms compared to the control group (P < 0.05); at Time 4 stage, the patients in the intervention group also demonstrated significantly improved quality-of-life scores compared to the control group (P < 0.05). Additionally, blood pressure and heart rate of patients returned to baseline levels at Time 4 stage, with no significant difference between the two groups (P > 0.05). Nevertheless, the anxiety and depression scores in the intervention group at the Time 4 stage remained significantly lower than those in the control group (P < 0.05). Additionally, the fear of disease progression scores in both groups were lower than those at the Time 1 stage, with a more pronounced improvement observed in the intervention group compared to the control group (P < 0.05).
CONCLUSIONS: Patients diagnosed with malignant tumors often experience fear and anxiety regarding the progression of their disease and upcoming surgery, as well as uncertainty surrounding their treatment and prognosis. This heightened emotional distress can contribute to a greater symptom burden during the perioperative period. Utilizing a whole-process visualization and collaborative nursing discussion approach, as compared to traditional communication methods, has been shown to alleviate patients\' fears, reduce anxiety and depression, and ultimately lessen the symptom burden experienced during the perioperative phase. Ultimately, this approach can enhance the overall quality of life for patients facing malignant tumors.

UNASSIGNED: To conduct a translation and validation study of the Chronic Orchialgia Symptom Index (COSI), which has 12 questions in three domains pain (P), sexual symptoms (SS), and quality of life (QoL), in the Turkish language.
UNASSIGNED: The study included a total of 175 patients diagnosed with chronic scrotal content pain (CSCP) between January 2023 and January 2024. In addition to demographic data, the scores obtained on the COSI questionnaire and Visual Analog Scale (VAS) were recorded. Internal consistency was assessed using Cronbach alpha coefficients. Reliability was evaluated using the test-retest correlation method.
UNASSIGNED: The mean age of the patients was 37.2 ± 14.1 years and the median (IQR) duration of pain was 5.5 (9) months. The median total COSI score was determined as 13 (13) and the median subscores were 7 (7) for P, 1 (2) for SS, and 5 (6) for QoL. The test-retest correlation coefficient for each item was determined to be higher than r = 0.80 (p < 0.001). The Cronbach alpha values for the subscores were 0.80 for P, 0.71 for SS, and 0.80 for QoL. There was determined to be a statistically significant positive correlation between the VAS score and the COSI P, SS, QoL, and total scores (r: 0.63, p < 0.001; r = 0.32, p < 0.001; r = 0.56, p < 0.001; r = 0.59, p < 0.001, respectively). The optimal cutoff point of the COSI total score was determined to be 16.5 points (AUC:0.77, p < 0.001) for the determination of patients experiencing severe pain (⩾ 7.5) according to the VAS score.
UNASSIGNED: The Turkish version of the COSI questionnaire is a valid, reliable, and repeatable questionnaire that can be used to evaluate the effects of symptom severity in patients with CSCP.

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities.
METHODS: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups.
RESULTS: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children.
CONCLUSIONS: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

Background: Elexacaftor-tezacaftor-ivacaftor (ETI) is a novel, highly effective CFTR modulator combination proven to enhance lung function and body weight in people with cystic fibrosis (pwCF) carrying a F508del mutation. Recently, we revealed significant reductions in abdominal symptoms (AS) in German, British, and Irish pwCF after 24-26 weeks of ETI using the CFAbd-Score, the first patient-reported outcome measure (PROM) specifically developed and validated for pwCF following FDA guidelines. Notably, many pwCF reported marked changes in their AS during the first days of the new treatment. To capture these immediate effects, we developed the CFAbd-day2day, a CF-specific GI-diary, following FDA and COSMIN guidelines. Aim: To prospectively capture the immediate dynamics of AS using the CFAbd-day2day 14 days before and 14-28 days after ETI initiation. In addition, we aim to provide validation steps of the novel PROM concerning sensitivity to changes. Methods: To develop the CFAbd-day2day, focus groups (community voice = pwCF and their proxies and CF specialists from different fields) were repeatedly consulted. Before and during the new ETI therapy, pwCF prospectively scored AS on a daily basis with the CFAbd-day2day. Results: Altogether, 45 pwCF attended in five CF centers prospectively completed the CFAbd-day2day before (mean ± sd:14 ± 7 days) and after (mean ± sd: 28 ± 23 days) ETI initiation. On the one hand, cumulative scores significantly decreased during the 3-4-week time frame after ETI initiation, compared to 2 weeks prior to therapy. On the other hand, many patients who revealed a relatively stable level of AS before ETI reported changes during the first days of treatment with the highly effective CFTR modulators. Factors like pain and flatulence increased in up to 21% of patients during the first 14 days of therapy, but they improved during days 15-27. Conclusion: The CFAbd-day2day, specifically developed and in the process of validation to prospectively capture GI symptoms in pwCF, provides new substantial insights into the dynamics of AS in pwCF receiving a new treatment with ETI. This novel tool is also helpful in prospectively monitoring patients with specific GI problems. International implementation and further validation steps of the diary are ongoing.

UNASSIGNED: Prognostics for patients with cancer is especially important for the supportive care of those who are terminally ill. We previously found that symptom scores as patient-reported outcomes (PROs)-such as dyspnea and fatigue scores-some biochemical parameters, the palliative performance scale (PPS) scores, and symptom clusters were useful prognostic factors; however, the predictability of a prognosis based on these factors remains unclear.
UNASSIGNED: To identify appropriate three-week survival predictive factor(s), in terms of performance, in patients who were terminally ill.
UNASSIGNED: We collected symptom scores as PROs using the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL).
UNASSIGNED: We used data from terminally ill patients with cancer who were hospitalized at the palliative care unit of the Higashisumiyoshi-Morimoto Hospital (Osaka, Japan) from June 2018 to December 2019 (n = 130), as well as additional data obtained from the same clinical study from January to March 2020 (n = 31).
UNASSIGNED: To evaluate predictive performance, indices such as sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated.
UNASSIGNED: We found that the presence of a symptom cluster showed high sensitivity but low specificity and that a higher PPS value (>30) showed high specificity but low sensitivity, suggesting that these factors could provide relevant information for survival prognosis (less than or equal to three weeks).
UNASSIGNED: Symptom clusters obtained from patients is important for effective supportive care of those who are terminally ill.

Chronic rhinosinusitis with nasal polyp (CRSwNP) is one of the major phenotypes of chronic rhinosinusitis (CRS) with a high symptom burden. Doxycycline can be used as add-on therapy in CRSwNP. We aimed to evaluate short-term efficacy of oral doxycycline on visual analog scale (VAS) and SNOT-22 (Sino-nasal outcome test) score for CRSwNP.
Visual analog score (VAS) for nasal symptoms and total SNOT-22 scores of 28 patients who applied with the diagnosis of CRSwNP and received 100 mg doxycycline for 21 days were analyzed in this retrospective cohort study. Doxycycline efficacy was also evaluated in subgroups determined according to asthma, presence of atopy, total IgE and eosinophil levels.
After 21-day doxycycline treatment, there was a significant improvement in VAS score for post-nasal drip, nasal discharge, nasal congestion, and sneeze, and total SNOT-22 score (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). No significant improvement was observed in VAS score for the loss of smell (p = 0.18). In the asthmatic subgroup, there were significant improvements in all VAS scores and total SNOT-22 score after doxycycline. In the non-asthmatic subgroup, there was no significant change in any of the VAS scores, but total SNOT-22 score was significantly improved (42 [21-78] vs. 18 [9-33]; p = 0.043). Improvement in VAS score for loss of smell is significant in only some subgroups like asthmatic patients, non-atopic patients, and patients with eosinophil >300 cell/µL.
Doxycycline can be considered as an add-on treatment for symptom control in patients especially with CRSwNP comorbid with asthma.

IgE-mediated atopic diseases such as allergic rhinitis and rhinoconjunctivitis are common chronic diseases in the western world. Allergen immunotherapy (AIT) plays a fundamental role in the treatment of allergic patients by modulating the underlying immune mechanisms. Though this treatment is integrated in practice-patterns globally, many differences are found in the application of AIT on the national or international level due to heterogeneous methods, and clinical recommendations are given in different parts of the world. This review from authors in Europe and the United States highlights differences and similarities in important aspects of AIT application in the 2 global regions. First, the regulatory situation differs regarding marketing authorization and licensing. Secondly, differences are elaborated in manufacturing practices, marketing distribution and formulations of AIT products. Thirdly, clinical administration patterns in the current guidelines show similarities in indications and contraindications of AIT, but also are divergent in some practical aspects. Informing the readership on similarities, as well as differences of standards in AIT in the United States and Europe, the authors highlight the unmet need of thorough harmonization of standards of AIT, as it is the only disease modifying treatment option available for patients with allergic rhinitis and rhinoconjunctivitis.

[This corrects the article DOI: 10.3389/fphar.2022.877118.].

Psychological disturbances are frequent following COVID-19. However, there is not much information about whether pre-existing psychological disorders are associated with the severity and evolution of COVID-19. We aimed to explore the associations between regular psychotropic medication use (PM) before infection as a proxy for mood or anxiety disorders with COVID-19 recovery trajectories. We used data from the Predi-COVID study. We followed adults, tested positive for SARS-CoV-2 and collected demographics, clinical characteristics, comorbidities and daily symptoms 14 days after inclusion. We calculated a score based on 16 symptoms and modeled latent class trajectories. We performed polynomial logistic regression with PM as primary exposure and the different trajectories as outcome. We included 791 participants, 51% were men, and 5.3% reported regular PM before infection. We identified four trajectories characterizing recovery dynamics: \"Almost asymptomatic,\" \"Quick recovery,\" \"Slow recovery,\" and \"Persisting symptoms\". With a fully adjusted model for age, sex, socioeconomic, lifestyle and comorbidity, we observed associations between PM with the risks of being in more severe trajectories than \"Almost Asymptomatic\": \"Quick recovery\" (relative risk (95% confidence intervals) 3.1 (2.7, 3.4), \"Slow recovery\" 5.2 (3.0, 9.2), and \"Persisting symptoms\"11.7 (6.9, 19.6) trajectories. We observed a gradient of risk between PM before the infection and the risk of slow or no recovery in the first 14 days. These results suggest that a pre-existing psychological condition increases the risk of a poorer evolution of COVID-19 and may increase the risk of Long COVID. Our findings can help to personalize the care of people with COVID-19.