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1.
J Fungi (Basel) ; 9(11)2023 Nov 04.
Article in English | MEDLINE | ID: mdl-37998886

ABSTRACT

The optimal prevention strategy for invasive aspergillosis (IA) in lung transplant recipients (LTXr) is unknown. In 2016, the Danish guidelines were changed from universal to targeted IA prophylaxis. Previously, we found higher rates of adverse events in the universal prophylaxis period. In a Danish nationwide study including LTXr, for 2010-2019, we compared IA rates in time periods with universal vs. targeted prophylaxis and during person-time with vs. person-time without antifungal prophylaxis. IA hazard rates were analyzed in multivariable Cox models with adjustment for time after LTX. Among 295 LTXr, antifungal prophylaxis was initiated in 183/193 and 6/102 during the universal and targeted period, respectively. During the universal period, 62% discontinued prophylaxis prematurely. The median time on prophylaxis was 37 days (IQR 11-84). IA was diagnosed in 27/193 (14%) vs. 15/102 (15%) LTXr in the universal vs. targeted period, with an adjusted hazard ratio (aHR) of 0.94 (95% CI 0.49-1.82). The aHR of IA during person-time with vs. person-time without antifungal prophylaxis was 0.36 (95% CI 0.12-1.02). No difference in IA was found during periods with universal vs. targeted prophylaxis. Prophylaxis was protective of IA when taken. Targeted prophylaxis may be preferred over universal due to comparable IA rates and lower rates of adverse events.

2.
APMIS ; 131(11): 574-583, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37022293

ABSTRACT

Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause morbidity among lung transplant recipients (LTXr). Early diagnosis and treatment could improve outcomes. We examined rates of CMV after IA and vice versa to assess whether screening for one infection is warranted after detecting the other. All Danish LTXr, 2010-2019, were followed for IA and CMV for 2 years after transplantation. IA was defined using ISHLT criteria. Adjusted incidence rate ratios (aIRR) were estimated by Poisson regression adjusted for time after transplantation. We included 295 LTXr, among whom CMV and IA were diagnosed in 128 (43%) and 48 (16%). The risk of CMV was high the first 3 months after IA, IR 98/100 person-years of follow-up (95% CI 47-206). The risk of IA was significantly increased in the first 3 months after CMV, aIRR 2.91 (95% CI 1.32-6.44). Numbers needed to screen to diagnose one case of CMV after IA, and one case of IA after CMV was approximately seven and eight, respectively. Systematic screening for CMV following diagnosis of IA, and vice versa, may improve timeliness of diagnosis and outcomes for LTXr.


Subject(s)
Aspergillosis , Cytomegalovirus Infections , Invasive Fungal Infections , Humans , Cytomegalovirus , Cohort Studies , Transplant Recipients , Risk Factors , Aspergillosis/epidemiology , Aspergillosis/etiology , Lung , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/complications , Antiviral Agents , Retrospective Studies
3.
Microorganisms ; 10(12)2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36557731

ABSTRACT

Background: Invasive fungal infections in lung transplant (LTX) recipients cause substantial morbidity, but the best strategy for prevention has not yet been determined. We evaluated adherence to and rates of adverse events of universal versus targeted prophylaxis. Methods: All LTX recipients in the Danish National LTX Centre (2010−2019) were included. Before July 2016, universal voriconazole prophylaxis was used. After July 2016, only high-risk patients received targeted prophylaxis with posaconazole and inhaled amphotericin B. Proportions of triazole discontinuation, side-effects, off-target calcineurin-inhibitor (CNI) levels, and acute rejection were compared between the two periods. Results: Universal and targeted prophylaxis was initiated in 183/193 and 6/102 patients, respectively. Only 37% completed > 9 of the intended 12 weeks of voriconazole; 72% of discontinuations were due to hepatotoxicity. In the universal vs. targeted prophylaxis period, 89% vs. 72% (p < 0.001) patients had low CNI episodes, and 37% vs. 1% (p < 0.001) of these were associated with discontinuation of triazole; 40% vs. 14% (p < 0.001) had acute rejection; and 23% vs. 3% (p < 0.001) had acute rejection associated with low CNI episodes. Conclusions: Universal voriconazole prophylaxis was associated with high rates of discontinuation, mainly caused by hepatotoxicity. In comparison to the targeted posaconazole period, more patients had low CNI levels and acute rejection in the universal voriconazole period.

4.
Transplant Proc ; 54(8): 2329-2336, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36127173

ABSTRACT

BACKGROUND: Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated. METHODS: We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models. RESULTS: A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07). DISCUSSION: Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.


Subject(s)
Anemia , Cystic Fibrosis , Kidney Transplantation , Lung Transplantation , Adult , Humans , Male , Kidney Transplantation/adverse effects , Retrospective Studies , Cystic Fibrosis/complications , Time Factors , Anemia/diagnosis , Anemia/epidemiology , Anemia/etiology , Risk Factors , Lung Transplantation/adverse effects
5.
J Clin Med ; 11(6)2022 Mar 09.
Article in English | MEDLINE | ID: mdl-35329822

ABSTRACT

BACKGROUND: Patients undergoing lung transplantation (LTx) experience a rapid decline in glomerular filtration rate (GFR) in the acute postoperative period. However, no prospective longitudinal studies directly comparing the performance of equations for estimating GFR in this patient population currently exist. METHODS: In total, 32 patients undergoing LTx met the study criteria. At pre-LTx and 1-, 3-, and 12-weeks post-LTx, GFR was determined by 51Cr-EDTA and by equations for estimating GFR based on plasma (P)-Creatinine, P-Cystatin C, or a combination of both. RESULTS: Measured GFR declined from 98.0 mL/min/1.73 m2 at pre-LTx to 54.1 mL/min/1.73 m2 at 12-weeks post-LTx. Equations based on P-Creatinine underestimated GFR decline after LTx, whereas equations based on P-Cystatin C overestimated this decline. Overall, the 2021 CKD-EPI combination equation had the lowest bias and highest precision at both pre-LTx and post-LTx. CONCLUSIONS: Caution must be applied when interpreting renal function based on equations for estimating GFR in the acute postoperative period following LTx. Simplified methods for measuring GFR may allow for more widespread use of measured GFR in this vulnerable patient population.

6.
J Heart Lung Transplant ; 39(6): 541-550, 2020 06.
Article in English | MEDLINE | ID: mdl-32061508

ABSTRACT

BACKGROUND: Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR). METHODS: In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks. RESULTS: The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m2 (95% CI: 0-24 ml/min/1.73 m2, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]). CONCLUSIONS: Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.


Subject(s)
Blood Pressure/physiology , Felodipine/administration & dosage , Glomerular Filtration Rate/drug effects , Kidney/physiopathology , Lung Transplantation , Calcium Channel Blockers/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies
7.
Ugeskr Laeger ; 181(15)2019 Apr 08.
Article in Danish | MEDLINE | ID: mdl-30990162

ABSTRACT

Lung transplantation (LTx) has been performed in Denmark since 1992, and chronic obstructive pulmonary disease and interstitial lung diseases are the major indications. All candidates are subject to an intensive evaluation before being accepted for LTx. Follow-up after transplantation is life-long and includes immunosuppressive medication with a high risk of side effects. The median survival in Denmark is 7.0 years. Chronic rejection is common, diagnosed by declining lung function, and it is the most important factor for morbidity and mortality. LTx requires dedicated personnel in an interdisciplinary organisation.


Subject(s)
Lung Diseases, Interstitial , Lung Transplantation , Pulmonary Disease, Chronic Obstructive , Denmark , History, 20th Century , History, 21st Century , Humans , Lung Transplantation/history , Retrospective Studies
8.
Scand J Pain ; 19(2): 271-277, 2019 04 24.
Article in English | MEDLINE | ID: mdl-30835097

ABSTRACT

Background and aims The relative contribution of patient-related factors and intraoperative nerve damage for the development of chronic pain after surgery is unclear. This study aimed to examine chronic pain after bilateral thoracotomy. We hypothesized, that individual patient-related risk factors would be important resulting in an intraindividual uniformity of pain and hyperphenomena between the two sides of the thorax. Methods Twenty patients who had undergone lung transplantation via bilateral thoracotomy 6-12 months previously were included from the Danish Lung Transplant program, Rigshospitalet, Denmark, from October 2016 to August 2017. All patients answered questionnaires about pain in and around the scar, completed the Neuropathic Pain Symptom Inventory, and underwent bedside examination for hyperphenomena (brush- and cold-evoked allodynia, pinprick hyperalgesia) and pinprick hypoalgesia. Results Nine patients reported spontaneous pain bilaterally, five patients had pain on one side only, and six patients had no pain. Hyperphenomena were present on both sides of the thorax in 13 patients, on one side in four patients, and three patients had no hyperphenomena. The intraindividual uniformity of pain (p=0.029) and hyperphenomena (p=0.011) between the two sides of the thorax suggests that patient-related factors play an important role in the development of chronic pain. Conclusions The results of the present study provide support for the hypothesis of an individual predisposition for the development of chronic pain after thoracotomy. Implications Patient-related risk factors contribute to the development of chronic pain after thoracotomy. This result most likely can be transferred to chronic pain after other surgical procedures and therefore help us understand risk factors for chronic pain after surgery.


Subject(s)
Chronic Pain/etiology , Lung Transplantation/adverse effects , Pain, Postoperative/etiology , Thoracotomy/adverse effects , Denmark , Female , Humans , Hyperalgesia/etiology , Hypesthesia/etiology , Male , Middle Aged , Pain Measurement , Pain, Postoperative/diagnosis , Surveys and Questionnaires , Touch
9.
J Heart Lung Transplant ; 33(7): 727-33, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24709270

ABSTRACT

BACKGROUND: Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal complications requiring laparotomy after transplantation with outcomes for patients at increased risk. METHODS: In this study we performed a retrospective analysis of data of patients who underwent lung transplantation at our institution from 2004 to 2012. The study period was limited to the first 90 days after transplantation. RESULTS: Lung transplantation was performed in 258 patients, including 51 patients with α1-anti-trypsin deficiency (A1AD). Seventy-eight patients (30%) had an X-ray of the abdomen, and 23 patients (9%) required laparotomy during the first 90 days after transplantation. Patients with A1AD comprised 20% of the total recipients, 23% (18 of 78) of the patients who had an abdominal X-ray performed (p = 0.40), and 48% (11 of 23) of the patients who required laparotomy (p < 0.001). More than 1 of every 5 patients (11 of 51) with A1AD required laparotomy at a median 8 days after transplantation, and the estimated odds ratio for laparotomy for A1AD patients was 5.74 (CI 2.15 to 15.35). In the group of patients with A1AD who required laparotomy, the estimated hazard ratio for death was 1.62 (CI 0.57 to 4.62), the stay in the intensive care unit was prolonged, but no significant difference was observed for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS: A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung transplantation. There was a trend toward a higher risk of death after laparotomy in patients with A1AD, and the length of stay in the intensive care unit was significantly prolonged, whereas the time on mechanical ventilation was unaffected.


Subject(s)
Gastrointestinal Diseases/surgery , Laparotomy/statistics & numerical data , Lung Transplantation , Postoperative Complications/surgery , Pulmonary Emphysema/etiology , Pulmonary Emphysema/surgery , alpha 1-Antitrypsin Deficiency/complications , Adolescent , Adult , Child , Female , Gastrointestinal Diseases/epidemiology , Humans , Incidence , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
10.
Ugeskr Laeger ; 173(39): 2403-7, 2011 Sep 26.
Article in Danish | MEDLINE | ID: mdl-21958481

ABSTRACT

This review studies the literature on the effects of parental presence during treatment of injured and acutely ill children. Parents wish to stay with their child, and clinicians increasingly find it beneficial, probably correlated with increased experience. Studies indicate that the treatment of the child is not compromised by parental presence but only a few quasi-randomised, quantitative studies have been published, and many circumstances concerning parental presence have not been investigated sufficiently.


Subject(s)
Child, Hospitalized , Critical Illness/therapy , Emergency Service, Hospital , Parents , Wounds and Injuries/therapy , Attitude of Health Personnel , Child , Child, Hospitalized/psychology , Humans , Parents/psychology , Professional-Patient Relations , Visitors to Patients/psychology
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