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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Relationship of family and personal history to the occurrence of depression in persons with Alzheimer's disease.

The authors tested the associations of family history and personal history of depression with mood disorders among patients with Alzheimer's disease (AD; N=161). Considered individually, a positive family history and a positive personal history each conferred increased risk for depression in AD. Conjointly, neither family nor personal history accounted for a substantial amount of the variance in syndromal depression after the onset of AD. Most depressed AD patients in this sample did not have a positive family history or a previous episode of depression. Our understanding of the etiology and course of depression and dementia may be augmented with further neuropsychological and brain-imaging studies of the neuropathological substrates shared by these illnesses.

Colour Doppler imaging of the ocular circulation in diabetic retinopathy.

PURPOSE: To measure blood flow velocity in the ophthalmic artery (OA) and central retinal artery (CRA) in patients with diabetic retinopathy. SUBJECTS AND METHODS: 62 age-matched subjects divided into 3 groups: nondiabetic controls (n=17); diabetics with no clinical retinopathy or background changes (n=24); diabetics with either pre-proliferative or proliferative retinopathy (n=21). Colour Doppler imaging was performed on supine patients by one masked observer using the Acuson 128 machine. RESULTS: There was a statistically significant (p<0.05) decrease in both the peak systolic velocity (PSV 0.073 m/s) and end diastolic velocity (EDV 0.014 m/s) of the central retinal artery in the pre-proliferative/proliferative group compared to the no retinopathy/background retinopathy group (PSV 0.096 m/s, EDV 0.024 m/s) and the control group (PSV 0.142 m/s, EDV 0.029 m/s). The resistance index of the ophthalmic artery was significantly increased in both the preproliferative/proliferative (0.81) and the no retinopathy/background group (0.81) compared to controls (0.72). CONCLUSION: Reduced blood flow velocity was found in the CRA of diabetic patients and appeared to become further reduced with the progression of retinopathy. This suggests that monitoring with Colour Doppler imaging may have predictive power in identifying those at greatest risk of developing sight threatening proliferative disease. The resistance index of the OA was increased in diabetics compared to controls.

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.

Blood flow velocity in the peripheral circulation of glaucoma patients.

Using the laser Doppler technique we measured finger blood flow velocity in 25 untreated primary open-angle glaucoma (POAG), 22 untreated low-tension glaucoma (LTG) and 19 age-matched normal subjects. Four blood flow measurements were recorded: baseline flow, after immersion in warm water for 2 min (40 degrees C maximum flow), after 10 s exposure to cold water (4 degrees C minimum flow) and time to recover to baseline flow after cold immersion. Significant differences between the LTG group and both the normal and POAG groups were found in a greater maximum flow (p = 0.03 and p = 0.01, respectively), a lower minimum flow (p = 0.04 and p = 0.03, respectively) and a longer recovery time to baseline flow (p = 0. 0001 for both the normal and POAG groups). A longer recovery time to baseline flow (p = 0.008) in POAG was the only difference between the normal and POAG groups. Both glaucoma groups had more systemic vascular disease than normal, and there were more smokers in the POAG group than normals. Subgroup assessment performed with migraine, vascular disease and smoking subjects excluded from the analysis did not alter the overall results. We conclude that systemic vasospasm is a strong feature of low-tension glaucoma.

Drug-induced ocular cicatricial pemphigoid: a series of clinico-pathological reports.

Ocular cicatricial pemphigoid is a slowly progressive disease of mucous membranes and skin of unknown but presumed autoimmune aetiology. We describe eight cases of presumed drug-induced cicatrising conjunctival changes simulating ocular cicatricial pemphigoid, following the chronic use of topical glaucoma medication. In three of four patients who underwent conjunctival biopsy of the inferior fornix, this revealed histopathological changes similar to ocular cicatricial pemphigoid.

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.