Long-Term Medical and Psychosocial Outcomes in Living Liver Donors.

Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such "long-term" outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long-term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor-reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well-being, as well as overall health-related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long-term outcomes in liver donors.

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2).

Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2).

Although single-center and cross-sectional studies have suggested a modest impact of liver donation on donor psychological well-being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL-2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0-3%), alcohol abuse (2-5%), and anxiety syndromes (2-3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well-being at various time points. We identified significant predictors for donors' perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data-driven follow-up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Between Scylla and Charybdis: charting an ethical course for research into financial incentives for living kidney donation.

New approaches to address the kidney scarcity in the United States are urgently needed. The greatest potential source of kidneys is from living donors. Proposals to offer financial incentives to increase living kidney donation rates remain highly controversial. Despite repeated calls for a pilot study to assess the impact of financial compensation on living kidney donation rates, many fear that financial incentives will exploit vulnerable individuals and cast the field of transplantation in a negative public light, ultimately reducing donation rates. This paper provides an ethical justification for conducting a pilot study of a federally regulated approach to providing financial incentives to living kidney donors, with the goal of assessing donors' perceptions.

Survival of HIV-positive individuals with hepatitis B and C infection in Michigan.

We sought to estimate mortality and associated factors in HIV-hepatitis co-infected individuals in Michigan using a retrospective cohort study. For the study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals were matched to hepatitis B and C cases. In the final Cox proportional hazards regression model, individuals of other [hazard ratio (HR) 2·2, 95% confidence interval (CI) 1·4-3·2] and black (HR 1·3, 95% CI 1·1-1·6) race had decreased survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2·1, 95% CI 1·6-2·6), men who have sex with men (MSM)/IDUs (HR 1·5, 95% CI 1·1-2·2), individuals with undetermined risk (HR 1·5, 95% CI 1·2-1·9) and heterosexual practices (HR 1·4, 95% CI 1·1-1·8) had decreased survival compared to MSM. Additionally, an interaction was found between current HIV status and co-infection. Mortality in HIV-hepatitis co-infected individuals remains a continuing problem. Our study can help in planning interventions to reduce mortality in HIV-infected individuals.

Opportunities for shared decision making in kidney transplantation.

Health researchers and policy-makers increasingly urge both patient and clinician engagement in shared decision making (SDM) to promote patient-centered care. Although SDM has been examined in numerous clinical settings, it has received little attention in solid organ transplantation. This paper describes the application of SDM to the kidney transplantation context. Several distinctive features of kidney transplantation present challenges to SDM including fragmented patient-provider relationships, the time-sensitive and unpredictable nature of deceased organ offers, decision-making processes by transplant providers serving as both organ guardians (given the organ scarcity) versus advocates for specific patients seeking transplantation, variable clinical practices and policies among transplant centers, and patients' potentially compromised cognitive status and literacy levels. We describe potential barriers to and opportunities for SDM, and posit that SDM is feasible, warranting encouragement in kidney transplantation. We propose strategies to promote and overcome obstacles to SDM in kidney transplantation. We contend that engagement in SDM can be facilitated by re-organization of clinical care, communication and education of providers and patients.

Hepatitis B and C co-infection in HIV/AIDS population in the state of Michigan.

A retrospective cohort study was conducted from 1 January 2006 to 31 December 2009 in Michigan to estimate the prevalence of HIV and hepatitis co-infection and identify associated factors. The prevalence of co-infection was 4.1% [95% confidence interval (CI) 3.8-4.5]. Multivariable logistic regression analysis revealed a significant association between co-infection and being male and: of Black race [odds ratio (OR) 2.0, 95% CI 1.2-3.6] and of Other race (OR 3.5, 95% CI 1.7-7.0) compared to Hispanic race. A significant association was found between co-infection and risk categories of blood products (OR 11.1, 95% CI 6.2-20.2), injecting drug user (IDU) (OR 3.6, 95% CI 2.7-4.8) and men who have sex with men/IDU (OR 3.4, 95% CI 2.4-4.9) in addition to two interactions; one between sex and current HIV status and the other between current HIV status and age at HIV diagnosis. Our results document the changing epidemiology of HIV-hepatitis co-infection which can guide preventive measures and interventions to reduce the prevalence of hepatitis co-infection.

Health status in young adults two decades after pediatric liver transplantation.

We conducted a cross-sectional study of patients who underwent pediatric liver transplant (LT) between 1988 and 1992 to evaluate long-term health status. Survivors completed socio-demographic, medical and Health-Related Quality of Life (HRQOL) surveys by mail including the SF-36v2, PedsQL™4.0 Generic Core Scale, PedsQL™ Cognitive Functioning Scale and PedsQL™3.0 Transplant Module. SF-36 scores were converted to SF6D-based utilities and risk factors for lower outcomes were assessed. Eighty-five of 171 patients had survived. Fifty-six were contacted with a response rate of 66%. Median age at LT was 0.86 years (IQR 0.58-3.0) and 64.3% had biliary atresia. Mean age at survey was 23.0 ± 4.4 years: 62% attended college, 68% lived with parents and 80% of those over 23 were employed. Patient health utilities were lower than norms (0.75 ± 0.12 vs. 0.82 ± 0.18, p < 0.01) and correlated with unemployment (p < 0.042), hospitalizations (p < 0.005) and lower education level (p < 0.016). Lower PedsQL™3.0 Transplant Module and PedsQL™ 4.0 Generic Core Scale scores correlated with unemployment (p = 0.006, p = 0.009) and hospitalizations (p = 0.006, p = 0.02). Pediatric transplant recipients who survive to adulthood have lower physical HRQOL, measurable transplant-related disability and lower health utility. Transplantation is life saving; however, physical and psychological sequelae continue to affect health status up to two decades later.

The impact of COVID-19 on cancer patients, their carers and oncology health professionals: A qualitative study.

OBJECTIVE: Cancer patients, carers and oncology health professionals have been impacted by the COVID-19 pandemic in many ways, but their experiences and psychosocial responses to the pandemic are still being explored. This study aimed to document the experience of Australians living with cancer, family carers, and Oncology health professionals (HPs) when COVID-19 first emerged. METHODS: In this qualitative study, participants (cancer patients currently receiving treatment, family carers and HPs) completed a semi-structured interview exploring their experiences of COVID-19 and the impact it had on cancer care. Participants also completed the Hospital Anxiety and Depression Scale (patients) and the Depression, Anxiety and Stress Scale (carers and HPs) to assess emotional morbidity. Thematic analysis was undertaken on qualitative data. RESULTS: 32 patients, 16 carers and 29 HPs participated. Qualitative analysis yielded three shared themes: fear and death anxiety, isolation, and uncertainty. For HPs, uncertainty incorporated the potential for moral distress and work-stress. Patients and carers scoring high on anxiety/depression measures were more likely to have advanced disease, expressed greater death anxiety, talked about taking more extreme precautionary measures, and felt more impacted by isolation. CONCLUSION: Cancer and COVID-19 can have compounding psychological impacts on all those receiving or giving care. PRACTICE IMPLICATIONS: Screening for distress in patients, and burnout in HPs, is recommended. Increased compassionate access and provision of creative alternatives to face-to-face support are warrented.

Ultrasound guided foam sclerotherapy: factors associated with outcomes and complications.

OBJECTIVES: In recent years ultrasound guided foam sclerotherapy (UGFS) has become an increasingly popular treatment for varicose veins. Although many published series detail the results of UGFS, little is known about the factors which are associated with outcomes and complications. The aim of this study was to identify these factors. DESIGN: A review of a prospectively collected database of UGFS which commenced in July 2007. METHODS: A successful outcome was defined as complete occlusion of the target vein on duplex scanning at follow-up. Eight factors were assessed to determine whether they were associated with outcomes and complications. These factors were age, gender, compliance with post-procedure compression hosiery, previous varicose vein surgery, single or multiple sites of injection, concentration of sclerosant, volume of sclerosant and pre-procedure severity score. RESULTS: Between July 2007 and July 2009, a total of 126 patients (60 men, 66 women) attended follow-up visits and had a post-procedure duplex scan. Targets for UGFS included the great saphenous vein (n = 75), small saphenous vein (n = 13) and anterior accessory great saphenous vein (n = 8). The remainder of procedures involved other veins or more than a single target vein. The median timing of follow-up was 3 months (range 1.5-14 months) with duplex scans revealing complete occlusion of the target vein in 79% of patients. The only factor associated with a successful outcome was compliance with post-procedure compression hosiery (p < 0.05). The most frequently encountered complications following UGFS were skin staining (28%), superficial thrombophlebitis (18%) and pain (14%). The only factor associated with post-UGFS complications was female gender (p < 0.05). When complications were analysed in isolation female gender was also significantly associated with skin staining (p < 0.05), but no other complication. CONCLUSIONS: These data suggest that compliance with post-procedure compression hosiery and gender are important factors associated with a successful outcome and reported complications following UGFS, respectively.

Predictors of poor treatment outcomes in multidrug-resistant tuberculosis patients: a retrospective cohort study.

OBJECTIVES: We aimed to determine the characteristics, treatment outcomes and risk factors for poor treatment outcomes among multidrug-resistant (MDR) tuberculosis (TB) patients in Khyber Pakhtunkhwa province, Pakistan. METHODS: A retrospective cohort study including all patients with MDR-TB who sought care at the MDR-TB unit in Peshawar was conducted between January 2012 and April 2014. Patients were followed until an outcome of TB treatment was recorded as successful (cured or completed) or unsuccessful. Binary logistic regression was used to identify predictors of poor outcome, i.e. unsuccessful treatment outcomes. RESULTS: Overall, 535 patients were included. The proportion of female subjects was relatively higher (n = 300, 56.1%) than male subjects. The mean (standard deviation) age of patients was 30.37 (14.09) years. Of 535 patients for whom treatment outcomes were available, 402 (75.1%) were cured, 4 (0.7%) completed therapy, 34 (6.4%) had disease that failed to respond to therapy, 93 (17.4%) died and two (0.4%) defaulted; in total, 129 (24.1%) had an unsuccessful outcome. We found three significant predictors of unsuccessful treatment during multivariate logistic regression: being married (odds ratio (OR) = 2.17, 95% confidence interval (CI) 1.01, 4.66), resistance to second-line drugs (OR = 2.61, 95% CI 1.61, 4.21) and presence of extensively drug-resistant TB (OR = 7.82, 95% CI 2.90, 21.07). CONCLUSIONS: Approximately 75% of the treatment success rate set by the Global Plan to Stop TB was achieved. Resistance to second-line drugs and presence of extensively drug-resistant TB are the main risk factors for poor treatment outcomes.

Altered Nuclear Expression of the Deubiquitylase BAP1 Cannot be Used as a Prognostic Marker for Canine Melanoma.

BRCA1-associated protein-1 (BAP1) is a nuclear localized deubiquitylating enzyme that belongs to the ubiquitin c-terminal hydrolase subfamily. The encoded protein is highly homologous between man and dogs, suggesting a functional significance preserved by evolution. BAP1 has multiple properties, including tumour suppressor activity. Loss of BAP1 function is implicated in the oncogenesis of several types of cancers including uveal, mucosal and some cutaneous melanomas in humans, as well as in mesothelioma. In this study we investigate the significance of BAP1 in canine melanoma. Nuclear BAP1 protein was detected in five canine oral melanoma cell lines using an antibody commonly used for analysis of human tissues. BAP1 loss of function mutations often lead to loss of nuclear BAP1 (nBAP1) expression in humans; this is associated with a poorer prognosis in uveal and mucosal melanoma. Therefore, as a prelude to a study evaluating the prognostic significance of nBAP1 expression in dogs, immunohistochemistry (IHC) was used to assess cases of canine melanoma for nBAP1 expression. In 89 cases where tumour cells were identified by melan-A labelling, 100% of tumour cells were positive for nBAP1 expression, including eight uveal tract and 29 oral mucosal melanomas. This finding indicates that BAP1 IHC cannot be used as a prognostic marker in canine uveal and mucosal melanoma. Moreover, this observation suggests that either BAP1 has a different functional significance in canine melanoma or that loss of BAP1 function is achieved by a different route. This is a novel finding that warrants further investigation to determine the comparative biological relevance.

Color Doppler imaging in untreated high- and normal-pressure open-angle glaucoma.

PURPOSE: To evaluate ocular blood flow velocity indices in untreated primary open-angle glaucoma (POAG) and normal pressure glaucoma (NPG). METHODS: Twenty-five untreated patients with NPG, 23 untreated patients with POAG, and 26 age-matched normal control subjects underwent color Doppler imaging for the measurement of blood flow velocity in the central retinal and ophthalmic arteries. Neither the patients nor the control subjects were using systemic beta-blockers or calcium channel blockers. After log transformation of non-normal data, group differences were compared with a one-way analysis of variance followed by unpaired t-test with the Bonferroni correction. Statistical significance was set at P < 0.05. RESULTS: The central retinal artery end diastolic velocity was significantly lower in patients with POAG than in normal subjects. The ophthalmic artery peak systolic velocity (PSV) was significantly greater in patients with POAG than in those with NPG and normal subjects. The resistance index (RI) of both the ophthalmic and central retinal arteries was significantly greater in patients with POAG than in normal subjects, and the central retinal artery RI was significantly greater in those with NPG than in normal subjects. Systemic pulse pressure and systolic blood pressure were significantly greater in patients with POAG compared with normal subjects. Multiple regression analysis showed a significant relation between ophthalmic artery PSV and intraocular pressure (but not with any of the cardiovascular parameters) in the POAG group. Chi-square analysis found significantly more systemic vascular disease in patients with NPG and POAG compared with that of normal subjects. CONCLUSIONS: There was an increased resistance to blood flow in the central retinal artery of untreated patients with NPG and POAG and also in the ophthalmic artery of patients with POAG. The ophthalmic artery peak systolic velocity was elevated in untreated patients with POAG. Altered ocular circulation (with different patterns of presentation) appears to be common to patients with NPG and patients with POAG.

Warming lignocaine reduces the pain of injection during peribulbar local anaesthesia for cataract surgery.

AIMS: To test if the simple technique of warming lignocaine reduces the pain of injection during local anaesthetic cataract surgery. METHODS: Sixty patients undergoing peribulbar local anaesthesia for cataract surgery were allocated randomly to receive either warm (37 degrees C) or cold (room temperature) plain 2% lignocaine for the injection. Pain was assessed subjectively by asking the patients to score their pain from 0 (no pain) to 10 (most severe pain imaginable). RESULTS: The mean pain score for the warm group was 2.3 (SD 1.3) in comparison with a mean score of 5.5 (1.0) for the cold group (p < 0.01). CONCLUSIONS: The process of warming lignocaine to 37 degrees C has been found to reduce significantly the pain of injection during peribulbar local anaesthesia. It is recommended that this technique be more widely adopted in order to minimise patient's discomfort.

Pattern of arterial involvement of the head, neck, and eyes in giant cell arteritis: three case reports.

The findings of two post-mortem examinations and one CT scan of patients with biopsy proved giant cell arteritis (GCA) are presented. The presence or absence of intracranial involvement in GCA is discussed.

Comparison of the efficacy of diclofenac and betamethasone following strabismus surgery.

AIMS: To compare the relative antiinflammatory potency and safety of topical diclofenac-gentamicin with betamethasone-neomycin following strabismus surgery. METHODS: A single centre, single observer, prospective, randomised, and double masked clinical trial of 25 children undergoing bilateral symmetrical horizontal strabismus surgery was carried out. One eye received diclofenac-gentamicin and the contralateral eye received betamethasone-neomycin; both treatments were instilled four times a day for 4 weeks postoperatively. Ocular inflammation was assessed at 1 and 4 weeks postoperatively, objectively by comparison with a photographic chart and subjectively by questionnaire. RESULTS: There was no statistically significant difference in the rate of resolution of the inflammatory response between each group at both visits. CONCLUSION: Diclofenac appears to be as effective as betamethasone in controlling postoperative inflammation following strabismus surgery and may offer a safer alternative to the use of topical steroids.

Reproducibility of pulsatile ocular blood flow measurements.

PURPOSE: Langham adapted the pneumotonometer to provide a waveform of the ocular pulse and using the heart rate derived values for pulsatile ocular blood flow. We have used a new pneumotonometer linked to an ocular blood flow system that has addressed several of the problems encountered with the Langham technique. METHODS: The reproducibility of this new method was assessed by measuring pulsatile ocular blood flow (mul/min) five times on one eye of 20 normal healthy volunteers (mean age 40 years; range 26-62) at one examination session. The test was conducted in the sitting position with the pneumotonometer probe mounted on a slit-lamp microscope. RESULTS: The mean pulsatile ocular blood flow was 633 +/- 180 mu/min. Statistical analysis using the intraclass correlation method showed there were no significant differences due to sessions for five recordings (p = 0.15) or, after excluding the two most extreme values, for three recordings (p = 0.49). There was no correlation noted between pulsatile ocular blood flow and age in a larger group (n = 49) of normal volunteers (mean age 61 years; range 26-72). CONCLUSION: We conclude that pulsatile ocular blood flow measurements with this new instrument are reproducible and may be applied to blood flow studies in ocular hypertension and glaucoma.

Orbital neurilemmoma: report of seven cases.

Neurilemmoma (schwannoma) has a predilection for the head and neck, especially the eighth cranial nerve in the cerebellopontine angle. It rarely occurs in the orbit, representing only 1% of orbital tumours. We report seven cases. The nerve of origin was identifiable in four cases. Two occurred within the inferior oblique muscle. Five were treated successfully by anterior or lateral orbitotomy without craniotomy and two required a combined cranio-orbitotomy. The majority of orbital neurilemmomas occur as discrete intraorbital lesions without intracranial extension and can be safely removed via orbitotomy alone.