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  • Immer F
  • Benden C
  • Elmer A
  • Krügel N
  • Nyfeler S
  • et al.
Swiss Med Wkly. 2020 Dec 31;150:w20447 doi: 10.4414/smw.2020.20447.

The Swiss stepwise shutdown approach in organ donation and transplantation helped to maintain a limited national organ procurement and vital organ transplant activity, avoiding a complete nationwide shutdown of organ donation and transplant activity.&nbsp.

  • Benden C
  • Haile S
  • Kruegel N
  • Beyeler F
  • Aubert JD
  • et al.
Swiss Med Wkly. 2020 Dec 31;150:w20451 doi: 10.4414/smw.2020.20451.
AIMS OF THE STUDY:

The impact of coronavirus disease 2019 (COVID-19) on patients listed for solid organ transplantation has not been systematically investigated to date. Thus, we assessed occurrence and effects of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on patients on the Swiss national waiting list for solid organ transplantation.

METHODS:

Patient data were retrospectively extracted from the Swiss Organ Allocation System (SOAS). From 16 March to 31 May 2020, we included all patients listed for solid organ transplantation on the Swiss national waiting list who were tested positive for SARS-CoV-2. Severity of COVID-19 was categorised as follows: stage I, mild symptoms; stage II, moderate to severe symptoms; stage III, critical symptoms; stage IV, death. We compared the incidence rate (laboratory-confirmed cases of SARS-CoV-2), the hospital admission rate (number of admissions of SARS-CoV-2-positive individuals), and the case fatality rate (number of deaths of SARS-CoV-2-positive individuals) in our study population with the general Swiss population during the study period, calculating age-adjusted standardised incidence ratios and standardised mortality ratios, with 95% confidence intervals (CIs).

RESULTS:

A total of 1439 patients were registered on the Swiss national solid organ transplantation waiting list on 31 May 31 2020. Twenty-four (1.7%) waiting list patients were reported to test positive for SARS-CoV-2 in the study period. The median age was 56 years (interquartile range 45.3–65.8), and 14 (58%) were male. Of all patients tested positive for SARS-CoV-2, two patients were asymptomatic, 14 (58%) presented in COVID-19 stage I, 3 (13%) in stage II, and 5 (21%) in stage III. Eight patients (33%) were admitted to hospital, four (17%) required intensive care, and three (13%) mechanical ventilation. Twenty-two patients (92%) of all those infected recovered, but two male patients aged >65 years with multiple comorbidities died in hospital from respiratory failure. Comparing our study population with the general Swiss population, the age-adjusted standardised incidence ratio was 4.1 (95% CI 2.7–6.0).

CONCLUSION:

The overall rate of SARS-CoV-2 infections in candidates awaiting solid organ transplantation was four times higher than in the Swiss general population; however, the frequency of testing likely played a role. Given the small sample size of affected patients, conclusions have to be drawn cautiously and results need verification in larger cohorts.

  • de Lima JB
  • Soares DDS
  • Ferrari F
  • Carvas Junior N
  • Carvalho G
  • et al.
BMJ Open. 2020 Dec 29;10(12):e044975 doi: 10.1136/bmjopen-2020-044975.
INTRODUCTION:

Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients.

METHODS AND ANALYSIS:

We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository.

ETHICS AND DISSEMINATION:

Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER:

CRD42020191192.

  • Watson C
  • Barlev A
  • Worrall J
  • Duff S
  • Beckerman R
J Drug Assess. 2020 Dec 24;10(1):18-26 doi: 10.1080/21556660.2020.1854561.
PURPOSE:

Cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) is a treatment for post-transplant lymphoproliferative disease (PTLD) following solid organ transplant (SOT) after failing rituximab, an aggressive and potentially fatal lymphoma. This study explores the humanistic and economic burden of CHOP-associated adverse events (AEs) in PTLD patients. Since PTLD is rare, searches included lymphoproliferative disease with lymphoma patients.

DESIGN:

This comprehensive literature review used the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol, pre-specifying the search strategy and criteria. CHOP-associated short-term AEs with an incidence of >4% were sourced from published literature and cancer websites to inform the search strategy. PubMed and EMBASE searches were used to identify humanistic and economic burden studies.

RESULTS:

PubMed and EMBASE searches identified 3946 citations with 27 lymphoma studies included. Studies were methodologically heterogeneous. Febrile neutropenia (FN) was the AE most encountered, followed by chemotherapy-induced (CI) anemia (A), infection, CI-nausea and vomiting, thrombocytopenia, and CI-peripheral neuropathy (PN). FN and infections were associated with significant disutility, increased hospitalization, and extended length of stay (LOS). Infections and CIPN significantly impacted the utility of patients and CIA-related fatigue showed reductions in quality of life (QoL). Many patients continue to have QoL deficits continued even after AEs were treated. Management costs varied greatly, ranging from nominal (CIPN) to over $100,000 in the USA for infections, EUR 10,290 in Europe for infections, or CAN$1012 in Canada for FN. Cost of outpatient care varied but had a lower economic impact compared to hospitalizations.

CONCLUSIONS:

Short-term AEs from CHOP in the lymphoma population were associated with substantial humanistic and economic burden.

  • Araújo AYCC
  • Almeida ERB
  • Lima LKES
  • Sandes-Freitas TV
  • Pinto AGA
  • et al.
Epidemiol Serv Saude. 2020 Dec 18;30(1):e2020754 doi: 10.1590/S1679-49742021000100016.
OBJECTIVE:

To describe organ donations and transplants in Ceará state, Brazil, following the declaration of the COVID-19 pandemic.

METHODS:

This was a descriptive study using data from the Brazilian Organ Transplantation Association. The number of donors and transplants from April to June 2020 was compared to the same period in 2019 and to the first quarter of 2020.

RESULTS:

In the first half of 2020, the state registered 72 effective donors, just 17 (23.6%) of whom related to the second quarter. Of the 352 transplants in the first half of 2020, 37 (10.7%) were performed in the second quarter. Compared with the period from April to June 2019, there was a reduction of 67.9% and 89.3% in the number of donors and transplants, respectively, in the same period of 2020.

CONCLUSION:

The number of donors and transplants in Ceará showed an important fall in the three months following the declaration of the COVID-19 pandemic, especially for kidney, heart and cornea transplants.

  • Westphal GA
  • Robinson CC
  • Cavalcanti AB
  • Gonçalves ARR
  • Guterres CM
  • et al.
Ann Intensive Care. 2020 Dec 14;10(1):169 doi: 10.1186/s13613-020-00787-0.
OBJECTIVE:

To contribute to updating the recommendations for brain-dead potential organ donor management.

METHOD:

A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, joined a task force formed by the General Coordination Office of the National Transplant System/Brazilian Ministry of Health (CGSNT-MS), the Brazilian Association of Intensive Care Medicine (AMIB), the Brazilian Association of Organ Transplantation (ABTO), and the Brazilian Research in Intensive Care Network (BRICNet). The questions were developed within the scope of the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors. The topics were divided into mechanical ventilation, hemodynamic support, endocrine-metabolic management, infection, body temperature, blood transfusion, and use of checklists. The outcomes considered for decision-making were cardiac arrest, number of organs recovered or transplanted per donor, and graft function/survival. Rapid systematic reviews were conducted, and the quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Two expert panels were held in November 2016 and February 2017 to classify the recommendations. A systematic review update was performed in June 2020, and the recommendations were reviewed through a Delphi process with the panelists between June and July 2020.

RESULTS:

A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong (lung-protective ventilation strategy, vasopressors and combining arginine vasopressin to control blood pressure, antidiuretic hormones to control polyuria, serum potassium and magnesium control, and antibiotic use), 11 as weak (alveolar recruitment maneuvers, low-dose dopamine, low-dose corticosteroids, thyroid hormones, glycemic and serum sodium control, nutritional support, body temperature control or hypothermia, red blood cell transfusion, and goal-directed protocols), and 1 was considered a good clinical practice (volemic expansion).

CONCLUSION:

Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak. The observed lack of robust evidence on the topic highlights the importance of the present guideline to improve the management of brain-dead potential organ donors.

  • Schmalz G
  • Garbade J
  • Kollmar O
  • Ziebolz D
BMC Oral Health. 2020 Dec 9;20(1):356 doi: 10.1186/s12903-020-01350-w.
BACKGROUND:

The physical oral health and dental behaviour of patients after solid organ transplantation (SOT) has repeatedly been reported as insufficient. The objective of this systematic review was to detect whether the oral health-related quality of life (OHRQoL) of patients after SOT is reduced compared to that of healthy individuals.

METHODS:

A systematic literature search was performed by two independent individuals based on the PubMed, Web of Science and Scopus databases by using the following search terms: "transplantation" AND "oral health-related quality of life". The findings were checked to determine eligibility, whereby publication prior to 31 October 2020, examination of adult patients (age at least 18 years) with SOT, reporting of an OHRQoL outcome and full text in English language were the prerequisites for inclusion in the qualitative analysis. Quality appraisal of the included studies was performed using the Agency for Healthcare Research and Quality methodology checklist.

RESULTS:

Seven of 25 studies that examined patients after kidney (3), heart (2), liver (1) and lung transplantation (1) were included. Four studies included healthy controls, and five studies included a cohort of patients before transplantation for comparison. Clinical oral health examinations were heterogeneous between groups. The majority of studies (5/7) applied the short form of the "Oral Health Impact Profile" (OHIP 14) to assess OHRQoL. The OHIP 14 values ranged between 1.7 and 8.9 across studies, indicating an unaffected or just slightly reduced OHRQoL. Only one study found better OHRQoL in patients after SOT compared to a group before SOT, and one study confirmed worse OHRQoL of SOT recipients compared to a healthy control. Only two studies revealed an association between OHRQoL and oral health parameters. Furthermore, two studies each found a relationship between OHRQoL and general health-related quality of life or disease-related parameters.

CONCLUSIONS:

Patients after SOT show an unaffected or only slightly reduced OHRQoL, which was mainly independent of the insufficient oral status. This might indicate a shift in the perception threshold for oral diseases and conditions caused by the general health burden related to the SOT.

  • Tan EK
  • Koh YX
  • Kee T
  • Juhari JB
  • Tan TE
  • et al.
Ann Transplant. 2020 Dec 8;25:e926992 doi: 10.12659/AOT.926992.

BACKGROUND In solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, coronavirus disease 2019 (COVID-19) can contribute to a severe clinical course and an increased risk of death. Thus, patients awaiting a SOT or HSCT face the dilemma of choosing between a life-saving treatment that presents a significant threat of COVID-19 and the risk of waitlist dropout, progression of disease, or mortality. The lack of established literature on COVID-19 complicates the issue as patients, particularly those with inadequate health literacy, may not have the resources needed to navigate these decisions. MATERIAL AND METHODS We conducted a standardized phone survey of patients awaiting SOT or HSCT to assess the prevalence of inadequate health literacy and attitudes toward transplant during the COVID-19 pandemic. RESULTS Seventy-one patients completed the survey, with a response rate of 84.5%. Regardless of health literacy, most waitlisted candidates recognized that the current pandemic is a serious situation affecting their care and that COVID-19 poses a significant risk to their health. Despite the increased risks, most patients reported they would choose immediate transplantation if there was no foreseeable end to the pandemic, and especially if the medical urgency did not permit further delay. There were no differences in responses across the patient waitlist groups for heart, kidney, liver, and stem cell transplant. CONCLUSIONS These findings can help transplant centers decide how transplantation services should proceed during this pandemic and can be used to educate patients and guide discussions about informed consent for transplant during the COVID-19 pandemic.

  • Martin Saborido C
  • Borobia AM
  • Cobas J
  • D'Antiga L
  • Frauca E
  • et al.
BMJ Open. 2020 Dec 3;10(12):e037721 doi: 10.1136/bmjopen-2020-037721.
INTRODUCTION:

Paediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children's health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies.

METHODS AND ANALYSIS:

We will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer-other, cancer-skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.

  • Rolid K
  • Andreassen AK
  • Yardley M
  • Gude E
  • Bjørkelund E
  • et al.
Am J Transplant. 2020 Dec;20(12):3538-3549 doi: 10.1111/ajt.16087.
CET Conclusion
Reviewer: Mr Simon Knight, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This manuscript reports 3-year outcomes from the HITTS study, which compared high intensity interval training (HIT) with moderate intensity continuous training for 9 months following cardiac transplantation. Unlike the 12-month results, the longer-term follow-up shows no difference in VO2-peak between the groups, with no difference in activity levels or intensity between groups. However, improvements in anaerobic threshold and muscle endurance in the HIT group were sustained. These results perhaps reflect the difficulty in maintaining exercise patterns outside the supervision of a clinical trial. However, it is encouraging that both groups had activity levels higher than a healthy normal population, suggesting that any form of sustained exercise program early post-transplant can have lasting effects on activity and fitness.
Aims: The aim of this study was to report the three-year follow-up data of the High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia (HITTS) study, which was an RCT comparing high-intensity interval training (HIT) with that of moderate intensity continuous training (MICT) for 9 months in de novo cardiac transplant patients.
Interventions: Patients were randomly assigned to HIT or MICT.
Participants: 81 de novo heart transplant recipients.
Outcomes: The primary outcome was the change in peak oxygen consumption VO2 peak (mL/kg/min). The secondary outcomes included heart rate response, body composition, muscle strength, heart function, daily physical activity, biomarkers and health-related quality of life.
Follow Up: 3 years

The randomized controlled High-Intensity Interval Training in De Novo Heart Transplant Recipients in Scandinavia (HITTS) study compared 9 months of high-intensity interval training (HIT) with moderate intensity continuous training in de novo heart transplant recipients. In our 3-year follow-up study, we aimed to determine whether the effect of early initiation of HIT on peak oxygen consumption (VO2peak ) persisted for 2 years postintervention. The study's primary end point was the change in VO2peak (mL/kg/min). The secondary end points were muscle strength, body composition, heart rate response, health-related quality of life, daily physical activity, biomarkers, and heart function. Of 78 patients who completed the 1-year HITTS trial, 65 entered our study and 62 completed the study tests. VO2peak increased from baseline to 1 year and leveled off thereafter. During the intervention period, the increase in VO2peak was larger in the HIT arm; however, 2 years later, there was no significant between-group difference in VO2peak . However, the mean change in the anaerobic threshold and extensor muscle endurance remained significantly higher in the HIT group. Early initiation of HIT after heart transplantation appears to have some sustainable long-term effects. Clinical trial registration number: NCT01796379.