Cognitive and psychiatric symptom trajectories 2-3 years after hospital admission for COVID-19: a longitudinal, prospective cohort study in the UK.

BACKGROUND: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study. FINDINGS: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20). INTERPRETATION: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19. FUNDING: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research.

P16 and HPV status in head and neck sarcomas and sarcomatoid carcinomas.

Human papillomavirus (HPV)-positive oropharyngeal carcinoma is a distinct type of head and neck carcinoma with improved prognosis. p16 immunostaining is often used as a surrogate marker for HPV infection in this particular setting. The aim of this study is to estimate the prevalence of p16 staining and HPV infection in head and neck sarcomatoid carcinomas as well as head and neck sarcomas. 21 sarcomatoid carcinomas and 28 head and neck sarcomas were tested for p16 positivity using immunohistochemical staining, and for high-risk HPV infection using In situ hybridization (ISH). 24 % of sarcomatoid carcinomas and 21 % of sarcomas were positive for p16 staining. All 49 cases were negative for HPV ISH. The results confirm that p16 staining is not specific and may not be associated with HPV infection in non-oropharyngeal head and neck sites. They also indicate that non-oropharyngeal head and neck sarcomatoid carcinomas are not likely to be HPV related.

Post-acute COVID-19 neuropsychiatric symptoms are not associated with ongoing nervous system injury.

A proportion of patients infected with severe acute respiratory syndrome coronavirus 2 experience a range of neuropsychiatric symptoms months after infection, including cognitive deficits, depression and anxiety. The mechanisms underpinning such symptoms remain elusive. Recent research has demonstrated that nervous system injury can occur during COVID-19. Whether ongoing neural injury in the months after COVID-19 accounts for the ongoing or emergent neuropsychiatric symptoms is unclear. Within a large prospective cohort study of adult survivors who were hospitalized for severe acute respiratory syndrome coronavirus 2 infection, we analysed plasma markers of nervous system injury and astrocytic activation, measured 6 months post-infection: neurofilament light, glial fibrillary acidic protein and total tau protein. We assessed whether these markers were associated with the severity of the acute COVID-19 illness and with post-acute neuropsychiatric symptoms (as measured by the Patient Health Questionnaire for depression, the General Anxiety Disorder assessment for anxiety, the Montreal Cognitive Assessment for objective cognitive deficit and the cognitive items of the Patient Symptom Questionnaire for subjective cognitive deficit) at 6 months and 1 year post-hospital discharge from COVID-19. No robust associations were found between markers of nervous system injury and severity of acute COVID-19 (except for an association of small effect size between duration of admission and neurofilament light) nor with post-acute neuropsychiatric symptoms. These results suggest that ongoing neuropsychiatric symptoms are not due to ongoing neural injury.

Wound Debridement in Pyoderma Gangrenosum.

BACKGROUND: Wound debridement improves healing in a variety of acute and chronic ulcers. However, there is concern that debridement may trigger pathergy and worsen pyoderma gangrenosum (PG). OBJECTIVE: To determine whether published evidence supports conservative wound debridement for PG. DATA SOURCES: The authors reviewed the literature published in MEDLINE through January 2023 using the search germs "pyoderma gangrenosum" and "debridement." STUDY SELECTION: Articles reporting sharp surgical debridement or maggot debridement for PG were included in the review. The authors also searched the reference sections of the reviewed articles for additional reports on debridement for PG. DATA EXTRACTION: Clinical data regarding patient status, procedures performed, and patient outcomes were extracted from the selected articles. DATA SYNTHESIS: There are multiple reports of uncontrolled, active-phase PG wounds worsening after aggressive excisional debridement of viable inflamed tissues. In contrast, there is no evidence indicating that conservative debridement of nonviable necrotic tissue worsens PG wounds, regardless of the disease activity. There are multiple reports of successful debridement and surgical grafting for PG in remission. CONCLUSIONS: There is no evidence in favor of or against using conservative debridement of nonviable necrotic tissue for a PG wound. Therefore, it should not be considered contraindicated, even in the active phase of the disease.

Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization.

Post-COVID cognitive deficits, including 'brain fog', are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends. Living systematic reviews produce rigorous, up-to-date and informative evidence summaries that are particularly important where research is emerging rapidly, current evidence is uncertain and new findings might change policy or practice. Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) aims to tackle the challenges of mental health science research by cataloguing and evaluating the full spectrum of relevant scientific research including both human and preclinical studies. GALENOS will also allow the mental health community-including patients, carers, clinicians, researchers and funders-to better identify the research questions that most urgently need to be answered. By creating open-access datasets and outputs in a state-of-the-art online resource, GALENOS will help identify promising signals early in the research process. This will accelerate translation from discovery science into effective new interventions for anxiety, depression and psychosis, ready to be translated in clinical practice across the world.

Setting national research priorities for difficult-to-treat depression in the UK between 2021-2026.

Background: Difficult-to-treat depression (DTD) presents a substantial health care challenge, with around one-third of people diagnosed with a depressive episode in the UK finding that their symptoms persist following treatment. This study aimed to identify priority research questions (RQs) that could inform the development of new and improved treatments, interventions, and support for people with DTD. Methods: Using an adapted Child Health and Nutrition Research Initiative (CHNRI) method, this national prioritisation exercise engaged 60 leading researchers and health care professionals in the UK, as well as 25 wider stakeholders with relevant lived experience to produce a ranked list of priority RQs in DTD. The final list of 99 distinct RQs was independently scored by 42 individuals against a list of five criteria: answerability, effectiveness, impact on health, deliverability, and equity. Results: Highly ranked RQs covered a range of novel and existing treatments. The three highest scoring RQs included evaluation of psychological and pharmacological therapies (eg, behavioural activation, and augmentation therapies), as well as social interventions to reduce loneliness or increase support for people with DTD. Conclusions: This exercise identified and prioritised 99 RQs that could inform future research and funding decisions over the next five years. The results of this research could improve treatment and support for people affected by DTD. It also serves as an example of ways in which the CHNRI method can be adapted in a collaborative manner to provide a more active role for patients, carers, and health care professionals.

Successful Treatment of Painful Cutaneous Vasculopathy With Rivaroxaban in a Patient With Systemic Lupus Erythematosus.

Novel oral anticoagulant (NOAC) medications have revolutionized hematology and cardiology. Recently, NOACs have demonstrated additional promise in dermatology. Specifically, rivaroxaban, a direct factor Xa inhibitor NOAC, has been shown to be successful in the treatment of livedoid vasculopathy. Herein, we describe a patient with systemic lupus erythematosus who presented with painful cutaneous vasculopathy, demonstrated on biopsy with occlusive microvascular fibrin thrombi without evidence of concurrent vasculitis. Interestingly, imaging and laboratory studies did not show evidence of hypercoagulability, arterial disease, or embolic disease. The patient’s vasculopathy and pain progressed despite antiplatelet therapy, often considered first-line in cases of microvascular occlusive disease. However, with rivaroxaban therapy, the patient experienced complete regression of her painful lesions, thereby supporting a further role for NOACs in cutaneous vasculopathy treatment. J Drugs Dermatol. 2020;19(5) doi:10.36849/JDD.2020.4684.

Trichoblastic carcinosarcoma: A case report and literature review.

Trichoblastic carcinosarcoma is a rare biphasic adnexal neoplasm. This case report chronicals the eighth occurrence of this tumor published in the English literature and provides a review of the prior publications. Clinically, this tumor presents as an isolated, rapidly growing lesion in elderly patients and is usually cured by complete surgical excision, with no evidence of recurrence or metastasis at follow-up (7/8 cases). Histopathologically, trichoblastic carcinosarcoma is dermal-based, with an epithelial component of basal cells and a mesenchymal component of spindle cells, both of which display malignant features. In addition to a morphologic description of trichoblastic carcinosarcoma, a discussion of the differential diagnoses, including other biphasic neoplasms, is also included. The small number of cases of trichoblastic carcinosarcoma is most likely secondary to under-recognition and underreporting and a larger case volume is needed to more accurately assess the clinical course and treatment strategies.

Controlling depth of electrosurgery after curettage of skin tumors-an in vitro study.

BACKGROUND: Depth of tissue injury in electrosurgery depends on generator power, electrode size, speed of electrode movement on tissue, and current delivery method. We sought to evaluate the depth of tissue injury associated with different methods of electrocoagulation in an effort to make electrocoagulation more reproducible. METHODS: A knife-shaped electrode was used to apply an electrosurgical current to the surface of a piece of bovine liver. Different electrosurgical methods were performed. Cross sections of the liver were then studied for tissue effect. RESULTS: Fulguration provided only superficial coagulation. Contact electrocoagulation and electrodesiccation using the flat side of the electrode provided significantly deeper levels of coagulation and were associated with less smoke than fulguration. Desiccation provided the deepest tissue effect. CONCLUSIONS: Electrofulguration can be used for superficial tissue destruction. For deeper coagulation, a relatively larger electrode can be used in contact mode. Slower movement of the electrode on tissue in contact mode is associated with desiccation and the deepest level of tissue destruction.

Management of fluid status and cardiovascular function in patients with diffuse skin inflammation.

Background: Skin inflammation causes vasodilation and increased vascular permeability, which may result in decreased blood pressure and peripheral edema. Patients with erythroderma usually compensate for low blood pressure with fluid retention and increased cardiac output. However, if the heart cannot support increased cardiac output, blood pressure will stay low, resulting in severe compensatory fluid retention, which leads to decompensated congestive heart failure, and pulmonary edema. Treatment for high-output congestive heart failure focuses on the primary pathology, which is skin inflammation. However, aggressive treatment of the inflammation with glucocorticoids may result in rapid resorption of extravascular fluid into the intravascular space and occurrence or aggravation of pulmonary edema. Erythrodermic patients with no clinical heart failure are also at risk for developing pulmonary edema if they receive glucocorticoids and/or intravascular fluids. Most hospitalists and dermatologists are not familiar with fluid administration and ways to manage cardiovascular function and blood pressure in patients with skin inflammation. Objectives and methods: In this article, we discuss the pathophysiology of vascular and fluid changes in the context of diffuse skin inflammation and provide some basic guidelines that can be presented to hospitalists by dermatologists. Limitations: Most of the recommendations and guidelines in the article are based on basic science and on the personal experience of the authors and are not supported by controlled trials. Capsule summary Diffuse skin inflammation causes major changes in the cardiovascular system and in the perfusion of internal organs. We provide guidelines for management of fluid status and cardiovascular function in patients with diffuse skin inflammation. Dermatologists can provide hospitalists or primary care providers with these guidelines to help them with creating better treatment plans.

Evolution of Iran's health research system over the past 50 years: a narrative review.

BACKGROUND: A substantial growth has been reported in Iran's health research output over the last recent decades, throughout the times of economic, social, and political instability. This study reviewed the existing literature to provide a better understanding of the evolution of Iran's health research system over this period. METHODS: A narrative review of studies addressing health research system (HRS) in Iran was performed. The search strategy and categorization of the retrieved data was informed by the HRS framework of the World Health Organization (WHO). This framework proposes four functions for HRS: (i) stewardship; (ii) financing; (iii) creating and sustaining resources; and (iv) producing and using research. Searches in MEDLINE through PubMed (using MeSH terms) complemented with semantic searches through PubMed and Google Scholar were conducted. RESULTS: After removing the duplicates, 805 articles were retrieved, of which 601 were irrelevant, and 204 were reviewed. CONCLUSIONS: Iran has made substantial progress in different components of its HRS over the last few decades, such as starting a discourse surrounding health research ethics, priority-setting, and placing monitoring mechanisms while increasing the capacity for conducting and publishing research. However, there is still room for improvements, or even a need for fundamental changes, in several components, such as regarding increasing the research budget and improving the funding allocation mechanisms; improving the education curriculum; and promoting the use of evidence. The findings emphasized that improvement of HRS functions requires addressing context-specific problems. This review provides essential lessons to share with other low- and middle-income countries and international organizations, eg, the WHO.

Setting research priorities to achieve long-term health targets in Iran.

BACKGROUND: In 2015, it was estimated that the burden of disease in Iran comprised of 19 million disability-adjusted life years (DALYs), 74% of which were due to non-communicable diseases (NCDs). The observed leading causes of death were cardiovascular diseases (41.9%), neoplasms (14.9%), and road traffic injuries (7.4%). Even so, the health research investment in Iran continues to remain limited. This study aims to identify national health research priorities in Iran for the next five years to assist the efficient use of resources towards achieving the long-term health targets. METHODS: Adapting the Child Health and Nutrition Research Initiative (CHNRI) method, this study engaged 48 prominent Iranian academic leaders in the areas related to Iran's long-term health targets, a group of research funders and policy makers, and 68 stakeholders from the wider society. 128 proposed research questions were scored independently using a set of five criteria: feasibility, impact on health, impact on economy, capacity building, and equity. FINDINGS: The top-10 priorities were focused on the research questions relating to: health insurance system reforms to improve equity; integration of NCDs prevention strategy into primary health care; cost-effective population-level interventions for NCDs and road traffic injury prevention; tailoring medical qualifications; epidemiological assessment of NCDs by geographic areas; equality in the distribution of health resources and services; current and future common health problems in Iran's elderly and strategies to reduce their economic burden; the status of antibiotic resistance in Iran and strategies to promote rational use of antibiotics; the health impacts of water crisis; and research to replace the physician-centered health system with a team-based one. CONCLUSIONS: These findings highlight consensus amongst various prominent Iranian researchers and stakeholders over the research priorities that require investment to generate information and knowledge relevant to the national health targets and policies. The exercise should assist in addressing the knowledge gaps to support both the National General Health Policies by 2025 and the health targets of the United Nations' Sustainable Development Goals by 2030.

50 years of Iranian clinical, biomedical, and public health research: a bibliometric analysis of the Web of Science Core Collection (1965-2014).

BACKGROUND: A substantial growth has been reported in Iran's number of clinical, biomedical, and public health research publications over the last 30 years. It is of interest to investigate whether this quantitative growth has also led to a larger number of papers with a high citation impact; to explore where the capacity for performing research lies; and which fields/institutions are lagging behind. METHODS: This was a bibliometric study. Web of Science Core Collection and its different tools were used for retrieving and analysing the publications. Information about the journals was found on Journal Citation Reports®. Different types of collaborations across the highly-cited papers was investigated based on the affiliations, the characteristics of the language of the authors' names, and the authors' study and work backgrounds. RESULTS: Iran's number of clinical, biomedical, and public health research publications has substantially increased since 2000, a surge was seen in 2007, and the figure reached a peak in 2011. 11% of the publications were in Pharmacology Pharmacy; and the majority originated in Tehran University of Medical Sciences. Six of the 10 journals that had published the most were Iranian journals. H-index of publications had also increased over time (almost doubled between 2000 and 2010). 30.9% of the most-cited publications had only relied on Iranian resources (including 48 publications); had been published in journals with impact factors ranging between 0.4 and 8.3; and the majority were original basic sciences research. CONCLUSIONS: In Iran, a great capacity for research lies in clinical, biomedical, and public health fields which can be strengthened with further investment. It is important to use this capacity in a way that would align with the national population health needs. It is also essential to consider the limitations of only relying on bibliometric tools for assessing health research activities. Finally, the Iranian science policy-makers are encouraged to (i) support the researchers and institutions that have proved research capacity; (ii) direct further resources towards research areas and/or institutions that are lagging behind; (iii) facilitate further international collaboration with the academics and/or institutions that have shown the capacity for conducting successful research projects with Iran.

T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism.

Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It typically presents with dermal papules or subcutaneous nodules, with no epidermal or upper papillary dermal involvement on histopathology. We present an unusual clinical presentation of leukemia cutis, with annular plaques and epidermotropism.

Effect of Self Care Education with and without Telephone Follow-Up on the Level of Hope in Renal Dialysis Patients: A Single-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Various strategies such as teaching self care to hemodialysis patients have been employed to increase the level of their hope. This study aimed at examining the effects of a telephone follow-up program on the level of hope in a self care education program. METHODS: In this single-blind randomized controlled clinical trial, 75 hemodialysis patients, selected by convenient sampling, were randomly assigned to 3 groups (n=25 each) including a control, a self care education, or a self care education with telephone follow-up. The control group received the routine care. The self care education group received 5 instruction sessions. The telephone follow-up group had similar instructional sessions followed by telephone calls during the subsequent 2 months. Data, collected using demographic information list and Miller's hope questionnaire, were analyzed using Chi-Square, t-test, and one-way ANOVA followed by Scheffee test. RESULTS: There was no significant difference among the scores of hope in the three groups before the intervention (P=0.40). However, after the intervention, the level of hope in the self care education group and self care education plus telephone follow-up groups were significantly higher than that of the control group (P=0.001). Moreover, the level of hope in the group with self care education plus telephone follow-up was significantly (P=0.001) more than that of the self care education group. CONCLUSION: Our findings indicated that teaching followed by telephone follow-up was associated with higher levels of hope. Therefore, such a strategy may be employed to improve the quality of life of patients with renal dialysis. TRIAL REGISTRATION NUMBER: IRCT2014042617440N1.