COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Objective measures of health-related quality of life over 24 months post-liver transplantation

Many studies have reported improved health-related quality of life (HRQoL) from pre- to immediate post-orthotopic liver transplantation (OLT). However, few studies have evaluated longitudinal changes over the first 2 yr post-OLT and none have simultaneously examined objective measures of health-related fitness. A total of 50 OLT recipients (32 males,18 females; 51.4 +/- 11.8 yr) completed testing at 2, 6, 12, and 24 months post-OLT. Testing included assessment of exercise capacity (peak VO2), quadriceps muscle strength, body composition, physical activity participation, and self-reported functioning (SF-36). Repeated measures of analysis of variance (ANOVA) with post hoc contrasts was performed to determine differences over time and a second ANOVA assessed differences over time between genders. All patients increased peak VO2, quadriceps muscle strength, and percent body fat (p < 0.0001) from 2 to 24 months. Men and women differed in their changes of peak VO2 and percent body fat (p < 0.05). At 24 months, only 50% of the patients reported participating in regular physical activity. All SF-36 physical measures except general health, improved from 2 to 24 months (p < 0.0001). Measures of health-related fitness and QoL improve over the first 2 yr post-OLT with the greatest gains occurring in the first 6 months and all measures remain lower than recommended for cardiovascular and overall health. A randomized clinical trial of lifestyle modifications such as diet and exercise intervention is warranted to determine the impact of such modifications on HRQoL and fitness post-OLT.     

Factors influencing change in health-related quality of life after liver transplantation

OBJECTIVE: To assess health-related quality of life (HRQoL) in patients following liver transplantation and the factors associated with HRQoL variation. METHODS AND MATERIALS: Sociodemographic and clinical data were collected for 60 consecutive patients activated for liver transplantation in a single hospital. Patients were classified according to the severity of the cirrhosis (Child-Pugh class) and disease etiology (alcoholic cirrhosis, viral cirrhosis, cholestatic diseases, and hepatocarcinoma). HRQoL was assessed by three different questionnaires: the Health Survey Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HAD), and a specific-symptom questionnaire. Questionnaires were completed during the pre-operative period and six months after transplantation. RESULTS: In the pre-operative period, patients with Child A had higher mean levels of HRQoL than did those in other groups. At six months following transplantation, there were no significant differences among the groups, largely because gains obtained by patients with Child B and C were much greater than those attained by patients with Child A. Across the four etiological groups, there were significant differences in all domains of the three questionnaires, except SF-36-bodily pain and HAD-anxiety, prior to transplantation, because patients with hepatocarcinoma had much better HRQoL. After transplantation, there were no differences because patients with viral and alcohol-induced cirrhosis achieved greater gains with respect to the neoplastic group. During the pre-operative period, the scores for all areas of the SF-36 and for all groups were below the general population normalized score of 50 (except for patients with Child class A and those affected with hepatocarcinoma). Six-months post-transplantation, the scores on most of the domains remained below 50, except for certain mental areas in which higher scores were attained. CONCLUSIONS: Health-related quality of life is influenced by the severity and etiology of cirrhosis-patients with Child class C and those with alcoholic or viral cirrhosis have the poorest quality of life. There were no differences observed among the groups after the transplantation, as the patients with the lowest HRQoLs prior to surgery demonstrated greater gains in HRQoL associated with liver transplantation.     

Do retrospective and prospective quality of life assessments differ for pancreas-kidney transplant recipients?

The literature indicates that chronically ill patients have a remarkable capacity to adapt to their illness. For example, they will generally report a better quality of life (QoL) than individuals in the general population who are asked to imagine themselves as chronically ill and to rate their QoL. The present study further explores this phenomenon in type I diabetic transplant recipients with end-stage renal disease. In a prospective, longitudinal study, we assessed the QoL in 22 patients, both before and after they received a combined pancreas-kidney transplant. After transplantation, the patients were also asked to assess their pretransplant QoL by rating it on a 10-point scale. What we found was that prior to transplantation, QoL was prospectively given a mean rating of 5.23; this score increased to 7 after a successful transplant procedure. During follow-up assessments 5, 12, and 18 months after successful transplantation, patients retrospectively scored their pretransplant QoL as 3.27, 3.14, and 3.05, respectively.We conclude that when type I diabetic patients with end-stage renal disease undergo a transplant procedure to improve their health status, they re-evaluate their pretransplant QoL, and this retrospective assessment is significantly lower than their prospective one when transplantation is successful. Received: 2 July 1997 Received after revision: 25 September 1997 Accepted: 10 October 1997     

Palliative and end of life care in solid organ transplantation

Palliative care is an interprofessional approach that focuses on quality of life of patients who are facing life‐threatening illness. Palliative care is consistently associated with improvements in advance care planning, patient and caregiver satisfaction, quality of life, symptom burden, and lower healthcare utilization. Most transplant patients have advanced chronic disease, significant symptom burden, and mortality awaiting transplant. Transplantation introduces new risks including perioperative death, organ rejection, infection, renal insufficiency, and malignancy. Numerous publications over the last decade identify that palliative care is well‐suited to support these patients and their caregivers, yet access to palliative care and research within this population are lacking. This review describes palliative care and summarizes existing research supporting palliative intervention in advanced organ failure and transplant populations. A proposed model to provide palliative care in parallel with disease‐directed therapy in a transplant program has the potential to improve symptom burden, quality of life, and healthcare utilization. Further studies are needed to elucidate specific benefits of palliative care for this population. In addition, there is a tremendous need for education, specifically for clinicians, patients, and families, to improve understanding of palliative care and its benefits for patients with advanced disease.     

New directions for induction immunosuppression strategy in solid organ transplantation

Background

Solid organ transplant centers are increasingly using induction immunosuppression strategies. Induction immunosuppression involves the use of intense therapy at the time of transplantation with the goal of preventing acute rejection and ultimately inducing a tolerogenic state. The objective of this review is to examine specialized induction agents currently in clinical use and highlight novel therapeutics on the horizon for induction immunosuppression.

Methods

A literature search using the PubMed and MEDLINE databases identified salient basic science and clinical research articles on induction immunosuppression for solid organ transplantation.

Conclusions

While current induction immunosuppression agents have reduced the incidence of acute rejection, the goal of transplant tolerance has not been realized. Furthermore, the long-term allograft survival rate is not clearly influenced by the practice of induction immunosuppression. New approaches to tolerance induction, such as costimulatory-based therapy, mixed chimerism, and adoptive cellular transfer, hold promise for more effective induction immunosuppression in solid organ transplantation.     

Adverse symptoms of immunosuppressants: A survey of Canadian transplant clinicians

Adverse symptoms of immunosuppressants (ASI) impact quality of life (QOL) in solid organ transplant recipients; however, standardized approaches for active ASI surveillance and intervention are lacking. While management is highly clinician dependent, clinician views remain largely unexplored. We surveyed Canadian Society of Transplantation members on their perceptions of ASI including frequency, perceived QOL impact, causal attribution, management strategies, and success. Sixty‐one clinicians participated in the survey of 12 ASI (tremor, diarrhea, nausea, constipation, dyspepsia, insomnia, edema, dyspnea, arthralgia, acne, mouth sores, paresthesias), for a 22% response rate. Forty‐nine completed the survey (80% completion rate). Diarrhea, dyspepsia, and insomnia were most frequent, requiring management in ≥ 2% of patients by 96%, 90%, and 82% of respondents, respectively. Diarrhea, insomnia, and dyspnea were deemed to have an important QOL impact by 92%, 82%, and 69%. Immunosuppressants were universally implicated as causative of tremor, diarrhea, acne, and mouth sores. Over 80% reported success in managing mouth sores, dyspepsia, and constipation. Management strategies included adjustment of immunosuppressant or other medications, drug therapy, and nonpharmacologic approaches and varied according to perceived causal attribution. More study is needed to compare clinician and patient views. These results will be used to establish priorities for further investigation of ASI.     

Predictors of health-related quality of life in hypertensive recipients following renal transplantation

BACKGROUND: Health-related quality of life (HRQoL) improves after renal transplantation. However, it is unclear which variables are the strongest determinants of HRQoL following renal transplantation. In this study, we wanted to assess whether antihypertensive medication, donor type, human leukocyte antigen (HLA)-compatibility or other variables could predict HRQoL 6-12 months after transplantation. METHODS: The study was a follow up of 124 patients recruited to a single center, randomized, double-blind clinical trial, comparing the effects of lisinopril and nifedipine in hypertensive renal transplant recipients. HRQoL was assessed with the Short Form 36 (SF-36) questionnaire. Bivariate and multiple linear regression analysis were used to assess the relationship between potential predictors and the physical component summary (PCS) and mental component summary (MCS) scales of the SF-36. RESULTS: Average scores 6-12 months after transplantation did not differ between patients randomized to lisinopril or nifedipine, or between cadaveric and living donor recipients on any of the eight SF-36 scales, or the two summary scales. In multivariate analyses, recipient age (p = 0.01) and cold ischemia time >14.5 h (p = 0.04) were independent predictors of the PCS score. Recipient age (p = 0.05), 2-4 HLA-AB mismatches (p = 0.05) and donor age (p = 0.03) were independent predictors of the MCS score. CONCLUSIONS: There was no evidence of differences in HRQoL according to lisinopril or nifedipine, or living vs. cadaveric donor transplantation. HRQoL was significantly reduced with longer cold ischemia time and more than one HLA-AB mismatches, after adjusting for age. These donor kidneys related issues need confirmation.     

Methodological issues in the assessment of health-related quality of life in palliative care trials

Palliative care aims at improving the patient's quality of life. Clinical trials, therefore, often include the patient's subjective evaluation of symptoms and psychosocial problems, so-called health-related quality of life (HRQL), as end-points. Unfortunately, there are frequently methodological weaknesses in the assessment of HRQL. This paper discusses four criteria which can be used in the evaluation of the quality of such studies: I. The authors should document that they have included the relevant HRQL issues in the questionnaire. If a trial misses important issues, its results may be misleading. II. The sample size should be sufficient to detect meaningful differences. Many trials are too small. III. The assessment of HRQL should have the appropriate timing, reflecting the research questions. The symptoms and the benefit resulting from treatments are not constant over time and often have cyclic patterns. The results may therefore be dependent on the timing of the administration of questionnaires to patients and on the time frames specified in the instructions. IV. The data must be reasonably complete. Incomplete data cannot be avoided in palliative care research, but missing data due to administrative failures or unrealistic schedules must be avoided. A pilot study may show whether a study is feasible. Missing data are likely to bias results. Many published palliative care studies are suboptimal with regard to one or more of these four criteria. This should be considered when reading published studies and when new trials are planned.     

The quality of reporting of randomized controlled trials in solid organ transplantation

Randomized controlled trials (RCTs) of interventions provide the highest level of evidence about efficacy but their value either alone or within a meta-analysis is dependent on its methodological quality. For this reason recent RCTs in organ transplantation were assessed for quality. RCTs published between 2004 and 2006 ( n  = 332) were assessed, after excluding duplicate and nonEnglish reports. Quality was evaluated using the Jadad score plus allocation concealment and intention to treat analysis. We noted journal type, journal author instructions, funding source, sample size and number and location of study centres. Around one-third of RCTs had a Jadad score of 3 or greater (indication of a methodologically good quality trial) and the other two parameters were satisfied in just over one third. Although the majority of trials were published in speciality journals the quality of those published in general journals was superior. Commercially sponsored trials were of better quality as were multicentre trials in contrast to single centre trials. Overall quality of reporting of RCTs in organ transplantation is poor and as RCTs provide the highest level of evidence in evaluations of interventions there needs to be a concerted effort within the transplant community to improve the standards of RCTs.     

Pain and health related quality of life after heart, kidney, and liver transplantation

No study has focused particularly on the sensory and affective experience of bodily pain among transplanted patients. The aim of this study was to explore pain and other factors that influence health related quality of life (HRQOL) in heart, kidney, and liver transplant recipients during the first 2 yr after transplantation, and to define similarities and/or differences in the three groups. A total of 76 patients, 18-60 yr old, undergoing heart, kidney, or liver transplantation between 1995 and 1997 with a follow-up of 6-24 months were included. HRQOL and pain were investigated by using the Short-Form-36 items (SF-36), the Hospital Anxiety and Depression Scale (HAD), and the Pain-O-Meter (POM). Overall, the patients show satisfactory HRQOL. There were no differences in experienced HRQOL 6 24 months after transplantation between kidney, liver, and heart transplant recipients except in the area of Role-Physical (RP). Fifty-three percent of all patients reported bodily pain. The most common locations were the hands, feet, and back, and sensory experiences were burning, stabbing, or dull pain. There was a correlation between number of rejections and total score for POM-VAS (p < 0.05) (rho = 0.47). There was also a correlation between the number of rejection episodes and the total pain intensity score for POM-WDS (p < 0.05) (rho = 0.48). Patients with pain scored higher in the area of depression (p < 0.05). Bodily pain is an important problem after organ transplantation, affecting daily living even in patients with good allograft function and it limits physical function. vitality, and general health.     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.     

Hematologic complications of anti-CMV therapy in solid organ transplant recipients

Abstract:  Cytomegalovirus (CMV) infection complicates the post-operative course of patients receiving solid organ transplants. While ganciclovir has significantly reduced the direct effects of CMV infection, some patients cannot tolerate the optimal therapeutic exposure required for CMV prevention and treatment. Few reports directly address the incidence, consequences, and risk factors for hematologic toxicities related to ganciclovir therapy. Nevertheless, leukopenia, thrombocytopenia, and anemia occur in 5–50% of patients. Current strategies, focused on ganciclovir dose reduction, may increase the risk of CMV reactivation and drug-resistant disease. The current article reviews the incidence, risk factors, and consequences of ganciclovir-associated hematologic adverse events in transplant recipients. Management strategies, including ganciclovir dose reduction, and the addition of CMV hyperimmune globulin are discussed. Exposing this relatively frequently occurring, but uncommonly discussed, toxicity should lead to better avoidance and treatment strategies, without placing patients at increased risk of CMV disease.     

Measurement properties of the short form 36 and health-related quality of life after intensive care in Morocco

BACKGROUND: Intensive care patients have a health-related quality of life (HRQL) that differs from the normal population. The aim of this study was to evaluate the measurement properties of the Arabic version of the short form (SF)-36 and study the HRQL determinants in adult patients 3 months after discharge from an intensive care unit (ICU). METHODS: A prospective cohort study after ICU discharge. At 3-month follow up, the SF-36 was administered in consultation or by telephone. Multitrait scaling analysis was used to confirm the hypothesized scale structure of the SF-36. Reliability was tested using (i) measuring internal consistency; and (ii) the test-retest reliability assessed using an intraclass correlation coefficient. Construct validity was tested by known-groups comparison using one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA). RESULTS: A total of 145 survivors answered the SF-36. Item internal convergency was higher than 0.40 (0.77-0.99; 100% scaling success) and item discriminant validity was perfect (100% scaling success) except for physical functioning (81% scaling success). Cronbach's alpha exceeded 0.70 in all eight scales (0.84-0.99). Test-retest reliability conducted in 73 patients was above 0.80. Acceptability to patients appeared reasonable although considerable interview time was required to administer the SF-36. Construct validity was confirmed by lower scores being reported by women, older age and a high level of comorbidities groups. When adjusted for background data, ICU variables were not associated with the SF-36 scores. CONCLUSIONS: The Arabic version of the SF-36 appears to be a robust tool in ICU. Background variables are the only significant determinants of HRQL 3 months after medical ICU discharge.     

Comparing quality of life following liver transplantation for Laennec's versus non-Laennec's patients

The overall success of orthotopic liver transplantation (OLTX) includes not only survival, but quality of life (QOL) as well. We studied one controversial group of OLTX recipients, patients transplanted for alcoholic liver disease (Laennec's), to determine if their post-OLTX QOL was similar to that of patients transplanted for non-alcoholic liver disease (non-Laennec's). Over a 10-yr period, patients undergoing OLTX at our institution were asked to complete a QOL questionnaire addressing a wide range of topics from demographics and employment to symptom distress/frequency, activities of daily living, and effect of loss of health on daily life. Twenty-four Laennec's and 100 non-Laennec's OLTX recipients completed the questionnaire at both their 2- and 5-yr follow-up visits at our institution. Both groups were well-matched in age, race, and patient location status at the time of OLTX. No significant differences could be detected between Laennec's and non-Laennec's scores regarding overall QOL, including one's ability to function, health perception, and self-perception at 2 and 5 years post-OLTX, and between 2 and 5 years post-OLTX. Although not between groups, a significant difference was noted regarding patients' satisfaction with life, with less satisfaction reported at the 5-yr versus the 2-yr time point post-OLTX. Rates of current/recent employment between both groups were also similar at 2 years post-OLTX, and again at 5 years post-OLTX. We conclude that overall QOL and employment levels appear similar between patients transplanted for alcoholic and non-alcoholic liver disease. This similarity appears to extend to 5 years post-OLTX.     

Life situation and quality of life in young adult kidney transplant recipients

Background. Young adults, 18–35 years of age, may be morevulnerable to chronic diseases than other age groups. In thisstudy we describe the life situation and lifestyle of youngadult kidney transplant recipients and compare their health-relatedquality of life (HRQoL) with a general population sample. Methods. Questionnaires, including items on life situation,lifestyle, and the SF-36 HRQoL questionnaire, were mailed toall 280 renal transplant recipients in Norway between 18 to35 years of age at the time of investigation of whom 131 (47%)responded. For comparison, we used 2,360 respondents aged 18to 35 years from a general population survey in one Norwegiancounty. SF-36 scores are presented with unadjusted scores andthe mean difference between groups adjusted for age, sex andeducation using multiple linear regression analysis. Results. The kidney transplant recipients reported high participationrates in cultural and sports activities, and the majority ofthem were satisfied with their work. A larger proportion ofthe transplant recipients had attained university educationthan the general population sample. However, 25% of the totalgroup were not integrated in professional life. The transplantrecipients scored lower than the general population on sevenof the eight SF-36 scales and the two summary scales after adjustingfor age, sex and education. Conclusions. The majority of young adult kidney recipients aged18–35 years were well adapted in their family and professionallife and satisfied with their current life situation. However,in aggregate they reported lower HRQoL on most scales of theSF-36 than a general population sample.