Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19: A Meta-analysis.

Importance: COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. Objective: To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. Data Sources: From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Study Selection: Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. Data Extraction and Synthesis: A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Main Outcomes and Measures: Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Results: Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. Conclusions and Relevance: This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.

A mixed methods study examining perceptions by service-users of their involuntary admission in relation to levels of insight.

BACKGROUND: Poor insight is associated with negative attitudes to involuntary admission and care in qualitative studies. AIMS: The current paper aims to examine and compare retrospective qualitative perceptions of service-users in relation to their involuntary admission with their levels of clinical insight, using a mixed methods approach. METHODS: Forty two participants were assessed 3 months after the revocation of their involuntary admission. Each provided qualitative data relating to their perceptions of the coercive care process, which was analysed using content analysis, along with a quantitative measurement of insight, the Schedule for the Assessment of Insight-Expanded (SAI-E). Employing a mixed methods design and incorporating NVivo matrix coding queries, the datasets were merged to enable qualitative themes to be identified against the quantitative data. RESULTS: Differences were observed between those with high and low insight in terms of their understanding of the need for treatment, their levels of arousal at the time of admission and how they perceived the compassion of health professionals. Certain negative perceptions of care appeared more universal and were common across those with high and low insight. CONCLUSION: Some negative perceptions of coercive practices appear linked to inherent elements of psychotic illness such as unawareness of illness. Individuals with higher levels of insight tended to perceive their involuntary admission and receiving a diagnosis as beneficial. Negative views that persist amongst service users with high insight levels can highlight areas for successful service improvement, including increased emphasis on non-pharmacotherapy based supports during the coercive care process.

Characteristics of High-Titer Convalescent Plasma and Antibody Dynamics After Administration in Patients With Severe Coronavirus Disease 2019.

We characterized the antibody composition of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) and the immunologic responses of hospitalized COVID-19 patients after receiving CCP or nonimmune fresh frozen plasma. Despite selection of CCP with significantly higher total immunoglobulin G than recipients, neutralizing antibody levels did not differ between donor plasma and CCP recipients.

Disseminated Legionella micdadei infection in a liver transplant patient presenting as pulmonary nodules and a laryngeal lesion.

We report a liver transplant patient with disseminated Legionella micdadei infection with pulmonary, laryngeal, and suspected muscle involvement. This organism, which stains weakly acid-fast, primarily affects immunocompromised patients. The diagnosis is difficult to make; in this case, the organism was identified via molecular diagnostics on laryngeal and pulmonary biopsy tissue.

Mycobacterium avium Complex Infection as a Rare Cause of Cerebral Mass Lesion and IRIS in a Patient With AIDS: Case Report and Review of the Literature.

A patient with advanced HIV/AIDS presented with a brain abscess. While brain biopsy culture and pathology were unrevealing, universal broad-range polymerase chain reaction (uPCR) demonstrated Mycobacterium avium complex (MAC). We review the clinicopathologic characteristics of MAC brain abscesses and highlight the effectiveness of uPCR as a diagnostic tool in partially treated infections.

Treatment of immunocompromised COVID-19 patients with convalescent plasma.

Immunosuppressed patients such as solid organ transplant and hematologic malignancy patients appear to be at increased risk for morbidity and mortality due to coronavirus disease 2019 (COVID-19) caused by SARS coronavirus 2 (SARS-CoV-2). Convalescent plasma, a method of passive immunization that has been applied to prior viral pandemics, holds promise as a potential treatment for COVID-19. Immunocompromised patients may experience more benefit from convalescent plasma given underlying deficits in B and T cell immunity as well as contraindications to antiviral and immunomodulatory therapy. We describe our institutional experience with four immunosuppressed patients (two kidney transplant recipients, one lung transplant recipient, and one chronic myelogenous leukemia patient) treated with COVID-19 convalescent plasma through the Expanded Access Program (NCT04338360). All patients clinically improved after administration (two fully recovered and two discharged to skilled nursing facilities) and none experienced a transfusion reaction. We also report the characteristics of convalescent plasma product from a local blood center including positive SARS-CoV-2 IgG and negative SARS-CoV-2 PCR in all samples tested. This preliminary evidence suggest that convalescent plasma may be safe among immunosuppressed patients with COVID-19 and emphasizes the need for further data on the efficacy of convalescent plasma as either primary or adjunctive therapy for COVID-19.

Clinical outcomes and serologic response in solid organ transplant recipients with COVID-19: A case series from the United States.

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS coronavirus 2 (SARS-CoV-2) has caused significant morbidity and mortality for patients and stressed healthcare systems worldwide. The clinical features, disease course, and serologic response of COVID-19 among immunosuppressed patients such as solid organ transplant (SOT) recipients, who are at presumed risk for more severe disease, are not well characterized. We describe our institutional experience with COVID-19 among 10 SOT patients, including the clinical presentation, treatment modalities, and outcomes of 7 renal transplant recipients, 1 liver transplant recipient, 1 heart transplant recipient, and 1 lung transplant recipient. In addition, we report the serologic response in SOT recipients, documenting a positive IgG response in all 7 hospitalized patients. We also review the existing literature on COVID-19 in SOT recipients to consolidate the current knowledge on COVID-19 in the SOT population for the transplant community.

Predictors of involuntary patients' satisfaction with care: prospective study.

BACKGROUND: Involuntary admission can be traumatic and is associated with negative attitudes that persist after the episode of illness has abated. AIMS: We aimed to prospectively assess satisfaction with care at the points of involuntary admission and symptomatic recovery, and identify their sociodemographic, clinical and service experience predictors. METHOD: Levels of satisfaction with care, and clinical and sociodemographic variables were obtained from a representative cohort of 263 patients at the point of involuntary admission and from 155 of these patients 3 months after termination of the involuntary admission. Data were analysed with multiple linear regression modelling. RESULTS: Higher baseline awareness of illness (B = 0.19, P < 0.001) and older age (B = 0.05, P = 0.001) were associated with more satisfaction with care at baseline and follow-up. Transition to greater satisfaction with care was associated with improvements in awareness of illness (B = 0.13, P < 0.001) and in symptoms (B = 0.05, P = 0.02), as well as older age (B = 0.04, P = 0.01). Objective coercive experiences were not associated with variation in satisfaction with care. CONCLUSIONS: There is wide variation in satisfaction with coercive care. Greater satisfaction with care is positively associated with clinical variables such as increased awareness of illness. DECLARATION OF INTEREST: None.

Individuals' experiences of involuntary admissions and preserving control: qualitative study.

BACKGROUND: A theoretical model of individuals' experiences before, during and after involuntary admission has not yet been established. AIMS: To develop an understanding of individuals' experiences over the course of the involuntary admission process. METHOD: Fifty individuals were recruited through purposive and theoretical sampling and interviewed 3 months after their involuntary admission. Analyses were conducted using a Straussian grounded theory approach. RESULTS: The 'theory of preserving control' (ToPC) emerged from individuals' accounts of how they adapted to the experience of involuntary admission. The ToPC explains how individuals manage to reclaim control over their emotional, personal and social lives and consists of three categories: 'losing control', 'regaining control' and 'maintaining control', and a number of related subcategories. CONCLUSIONS: Involuntary admission triggers a multifaceted process of control preservation. Clinicians need to develop therapeutic approaches that enable individuals to regain and maintain control over the course of their involuntary admission. DECLARATION OF INTEREST: None.

Service Users' Experiences of Involuntary Hospital Admission Under the Mental Health Act 2001 in the Republic of Ireland.

OBJECTIVE: The objective of the study was to explore the experiences of individuals admitted to the hospital involuntarily under the Mental Health Act 2001 in the Republic of Ireland. METHODS: In this qualitative descriptive study, 50 individuals who had been involuntarily admitted to a hospital underwent face-to-face semistructured interviews approximately three months after revocation of the involuntary admission order. Data were analyzed by using an inductive thematic process. RESULTS: Participants reported mixed experiences over the course of the admission, with both positive and challenging aspects. Participants reported feeling coerced, disempowered, and unsupported at various stages of the admission and highlighted the long-term deleterious impact on their psychological well-being. However, participants also described encounters with individuals who endeavored to initiate a collaborative, informative, and compassionate approach. Four key themes emerged consistently across the trajectory of participants' involuntary admission experiences: feeling trapped and coerced, feeling disengaged and unsupported, admission-induced distress, and person-centered encounters. CONCLUSIONS: This qualitative study of service users' views across the entire trajectory of their involuntary admission identified a number of factors that should be addressed to reduce the negative impact of involuntary admission. A multifaceted strategy could include ongoing education and training of all stakeholders in the principles and practices of person-centered care, repeated provision of accessible information and emotional support to service users during all stages of involuntary admission, and a shift in culture to one that minimizes the traumatic impact of forced detention on individuals' psychological well-being.

Caregiver burden and distress following the patient's discharge from psychiatric hospital.

Aims and method Caring for someone with a mental illness is increasingly occurring within the community. As a result, family members who fulfil a caregiving role may experience substantial levels of burden and psychological distress. This study investigates the level of burden and psychological distress reported by caregivers after the patient's admission. Results This study found that the overall level of burden and psychological distress experienced by caregivers did not differ according to the patient's legal status. However, the caregivers of those who were voluntarily admitted supervised the person to a significantly greater extent than the caregivers of those who were involuntarily admitted. Approximately 15% of caregivers revealed high levels of psychological distress. Clinical implications This study may emphasise a need for mental health professionals to examine the circumstances of caregivers, particularly of those caring for patients who are voluntarily admitted, a year after the patient's admission.

Qualitative exploration of stakeholders' perspectives of involuntary admission under the Mental Health Act 2001 in Ireland.

There is international interest in, and continued concern about, the potential long-term impact of involuntary admission to psychiatric institutions, and the effect this coercive action has on a person's well-being and human rights. Involuntary detention in hospital remains a controversial process that involves stakeholders with competing concerns and who often describe negative experiences of the process, which can have long-lasting effects on the therapeutic relationship with service users. The aim of the present study was to explore the perspectives of key stakeholders involved in the involuntary admission and detention of people under the Mental Health Act 2001 in Ireland. Focus groups were used to collect data. Stakeholders interviewed were service users, relatives, general practitioners, psychiatrists, mental health nurses, solicitors, tribunal members, and police. Data were analysed using a general inductive approach. Three key categories emerged: (i) getting help; (ii) detention under the Act; and (iii) experiences of the tribunal process. This research highlights gaps in information and uncertainty about the involuntary admission process for stakeholders, but particularly for service users who are most affected by inadequate processes and supports. Mental health law has traditionally focussed on narrower areas of detention and treatment, but human rights law requires a greater refocussing on supporting service users to ensure a truly voluntary approach to care. The recent human rights treaty, the UN Convention on the Rights of Persons with Disabilities, is to guarantee a broad range of fundamental rights, such as liberty and integrity, which can be affected by coercive processes of involuntary admission and treatment.

Caregivers' perceptions of coercion in psychiatric hospital admission.

While knowledge on service users' perspective on their admissions to psychiatric wards has improved substantially in the last decade, there is a paucity of knowledge of the perspectives of caregivers. This study aimed to determine caregiver's perception of the levels of perceived coercion, perceived pressures and procedural justice experienced by service users during their admission to acute psychiatric in-patient units. The perspective of caregivers were then compared to the perspectives of their related service users, who had been admitted to five psychiatric units in Ireland. Caregivers were interviewed using an adapted version of the MacArthur admission experience interview. Sixty-six caregivers participated in this study and the majority were parents. Seventy one percent of service users were admitted involuntarily and nearly half had a diagnosis of schizophrenia or schizoaffective disorder. Caregivers of involuntarily admitted individuals perceived the service users' admission as less coercive than reported by the service users. Caregivers also perceived a higher level of procedural justice in comparison to the level reported by service users. Reducing the disparity of perceptions between caregivers and service users could result in caregivers having a greater understanding of the admission process and why some service users may be reluctant to be admitted.

Increases in triglyceride levels are associated with clinical response to clozapine treatment.

Increases in serum triglyceride (TG) levels are associated with clinical response to clozapine treatment. Clozapine is the most efficacious therapy for treatment of refractory schizophrenia, although its use is well recognised to be associated with substantial metabolic dysfunction. Interestingly, there is some evidence that the therapeutic benefit of clozapine is associated with treatment-emergent weight gain and dyslipidaemia, specifically hypertriglyceridaemia. In this prospective observational study, we examine associations between therapeutic response to clozapine in 49 patients with treatment-resistant schizophrenia and lipid dysregulation. An increase in TG levels was strongly predictive of clinical improvement (B=9.33, t =3.56, df=4, p<0.001) and of improvement in positive PANSS scores (B=2.85, t=3.61, df=4, p=0.001) as well as negative PANSS scores (B=1.93, t=2.36, df=4, p=0.02), when controlling for potential confounds of weight gain, change in waist circumference, baseline antipsychotic polypharmacy and serum clozapine levels. This finding suggests that clozapine's therapeutic efficacy is linked to serum lipid changes. Hypertriglyceridaemia as a predictor of clinical response in patients treated with clozapine merits further investigation in order to better elucidate its effect on the pharmacological activity of clozapine.

Facilitating improvement in primary care: the promise of practice coaching.

Practice coaching, also called practice facilitation, assists physician practices with the desire to improve in such areas as patient access, chronic and preventive care, electronic medical record use, patient-centeredness, cultural competence, and team-building. This issue brief clarifies the essential features of practice coaching and offers guidance for health system leaders, public and private insurers, and federal and state policymakers on how best to structure and design these programs in primary care settings. Good-quality evidence demonstrates that practice coaching is effective. The authors argue that primary care delivery in the United States would benefit from a more systematic approach to the training and deployment of primary care practice coaches.

Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy.

The tumor microenvironment consists of stromal cells and extracellular factors that evolve in parallel with carcinoma cells. To gain insights into the activities of stromal cell populations, we developed and applied multicolor imaging techniques to analyze the behavior of these cells within different tumor microenvironments in the same live mouse. We found that regulatory T-lymphocytes (Tregs) migrated in proximity to blood vessels. Dendritic-like cells, myeloid cells and carcinoma-associated fibroblasts all exhibited higher motility in the microenvironment at the tumor periphery than within the tumor mass. Since oxygen levels differ between tumor microenvironments, we tested if acute hypoxia could account for the differences in cell migration. Direct visualization revealed that Tregs ceased migration under acute systemic hypoxia, whereas myeloid cells continued migrating. In the same mouse and microenvironment, we experimentally subdivided the myeloid cell population and revealed that uptake of fluorescent dextran defined a low-motility subpopulation expressing markers of tumor-promoting, alternatively activated macrophages. In contrast, fluorescent anti-Gr1 antibodies marked myeloid cells patrolling inside tumor vessels and in the stroma. Our techniques allow real-time combinatorial analysis of cell populations based on spatial location, gene expression, behavior and cell surface molecules within intact tumors. The techniques are not limited to investigations in cancer, but could give new insights into cell behavior more broadly in development and disease.