Investigators from the Seattle Cancer Care Alliance describe their implementation of a Death with Dignity program in compliance with Washington State law.
In 1997, Oregon became the first state in ...the United States to pass legislation that offered a “physician-assisted” approach to dying for adults with poor short-term prognoses.
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The Washington State legislature followed Oregon more than a decade later, passing an almost identical law, the Washington Death with Dignity Act, in November 2008.
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Under the law, competent adults residing in Washington who have a life expectancy of 6 months or less because of a diagnosed medical condition may request and self-administer lethal medication prescribed by a physician (Table 1).
As of December 2011, a total of 255 patients had participated in . . .
ABSTRACT
Introduction: This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR‐FAP). Methods: Prevalence estimates and information supporting ...prevalence calculations was extracted from records yielded by reference‐database searches (2005–2016), conference proceedings, and nonpeer reviewed sources. Prevalence was calculated as prevalence rate multiplied by general population size, then extrapolated to countries without prevalence estimates but with reported cases. Results: Searches returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding prevalence for 10 “core” countries, then extrapolated to 32 additional countries. ATTR‐FAP prevalence in core countries, extrapolated countries, and globally was 3,762 (range 3639–3884), 6424 (range, 1,887–34,584), and 10,186 (range, 5,526–38,468) persons, respectively. Discussion: The mid global prevalence estimate (10,186) approximates the maximum commonly accepted estimate (5,000–10,000). The upper limit (38,468) implies potentially higher prevalence. These estimates should be interpreted carefully because contributing evidence was heterogeneous and carried an overall moderate risk of bias. This highlights the requirement for increasing rare‐disease epidemiological assessment and clinician awareness. Muscle Nerve 57: 829–837, 2018
We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the ...cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 standard deviation {SD} 21.0; inter-quartile range {IQR}14.7) and diagnosis (mean 53.4 SD 21.0; IQR 14.7). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.
Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a ...pulmonary pathogen is unclear.
We tested BALF for HHV-6B DNA using polymerase chain reaction in allogeneic hematopoietic cell transplantation (HCT) recipients who underwent a BAL for evaluation of LRTD from 1992 to 2015. We used multivariable proportional hazards models to evaluate the association of HHV-6B
BALF with overall mortality, death from respiratory failure, and the effect of anti-HHV-6B antivirals on these outcomes. We used branched-chain RNA in situ hybridization to detect HHV-6 messenger RNA (
and
transcripts) in lung tissue.
We detected HHV-6B
BALF from 147 of 553 (27%) individuals. Subjects with HHV-6B
BALF, with or without copathogens, had significantly increased risk of overall mortality (adjusted hazard ratio aHR, 2.18; 95% CI, 1.41-3.39) and death from respiratory failure (aHR, 2.50; 95% CI, 1.56-4.01) compared with subjects with HHV-6B
BALF. Subjects with HHV-6B
BALF who received antivirals within 3 days pre-BAL had an approximately 1 log
lower median HHV-6B BALF viral load, as well as a lower risk of overall mortality (aHR, 0.42; 95% CI, 0.16-1.10), compared with subjects with HHV-6B
BALF not receiving antivirals. We detected intraparenchymal HHV-6 gene expression by RNA in situ hybridization in lung tissue in all three tested subjects with HHV-6B
BALF and sufficient tissue RNA preservation.
These data provide evidence that HHV-6B detection in BALF is associated with higher mortality in allogeneic hematopoietic cell transplantation recipients with LRTD. Definitive evidence of causation will require a randomized prevention or treatment trial.
On January 20, 2020, the first patient with coronavirus disease 2019 (COVID-19) in the United States of America was diagnosed in Washington state, which subsequently experienced rapidly increasing ...numbers of COVID-19 cases, hospitalizations, and deaths. This placed the Seattle Blood and Marrow Transplant Program at Fred Hutchinson Cancer Research Center (Fred Hutch) in the national epicenter of this pandemic. Here, we summarize the experience gained during our rapid response to the COVID-19 pandemic. Our efforts were aimed at safely performing urgent and potentially life-saving stem cell transplants in the setting of pandemic-related stresses on healthcare resources and shelter-in-place public health measures. We describe the unique circumstances and challenges encountered, the current state of the program amidst evolving COVID-19 cases in our community, and the guiding principles for recovery. We also estimate the collateral impact of directing clinical resources toward COVID-19-related care on cancer patients in need of stem cell transplantation. Although our experience was influenced by specific regional and institutional factors, it may help inform how transplant programs respond to COVID-19 and future pandemics.
Background and objectives
D‐negative patients are at risk of developing an alloantibody to D (anti‐D) if exposed to D during transfusion. The presence of anti‐D can lead to haemolytic transfusion ...reactions and haemolytic disease of the newborn. Anti‐D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti‐D alloimmunization with special attention in patients considered for HSCT.
Methods and materials
To understand transfusion practices regarding D‐positive platelets in D‐negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN®).
Results
Nineteen centres responded (68%). Most centres (79%) avoid transfusing D‐positive platelets to RhD‐negative patients when possible. Four centres (21%) avoid D‐positive platelets only in D‐negative women of childbearing age. If a D‐negative patient receives a D‐positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D‐negative patients who are HSCT candidates including adult men and women of no childbearing age.
Conclusion
There is wide variation in platelet transfusion practices for supporting D‐negative patients. The majority of centres do not have D‐positive platelet transfusion policies focused on preventing anti‐D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti‐D alloimmunization in HSCT patients.
Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events ...(irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC).
A 66-year-old man with recurrent metastatic MCC involving several organs (liver, bones and disseminated retroperitoneal lymphadenopathy) developed profound pharyngeal dysphagia and ileus that started 7 days after receiving a single administration of combination immune checkpoint blockade consisting of nivolumab (3 mg/kg) and low-dose ipilimumab (1 mg/kg). A swallowing study showed oropharyngeal dysfunction and aspiration. Imaging studies were consistent with diffuse intestinal paresis. An extensive work-up did not reveal obvious causes of these symptoms, and enteric plexopathy was suspected. Empiric immune suppressive therapy was initiated urgently. Despite an escalating immunosuppressive regimen that included high dose steroids, tacrolimus and therapeutic plasma exchange, no improvement in GI motility was seen and the patient suffered repeated episodes of aspiration. Seven weeks after the onset of GI hypomotility, the patient succumbed to sepsis from intestinal perforations. At autopsy, histologic specimens obtained from the entire GI tract (pharynx to rectum) showed near complete loss of ganglion cells within the myenteric and submucosal plexuses. An associated inflammatory infiltrate was not seen, suggesting a 'burned out' phase of illness. C4d complement deposition was found at the ganglionic sites, suggesting antibody-mediated pathogenesis. Remarkably, at sites of previously suspected Merkel cell metastases, no residual viable Merkel cell carcinoma was identified.
GI-tract paresis due to myenteric neuritis is a rarely reported toxicity of ICIs. Because the window of reversibility is likely to be very brief, quick and decisive interventions are warranted. Subtle functional and anatomic perturbations of the myenteric nervous system from the use of ICIs may be more prevalent than realized and should be suspected and addressed in both clinical and investigational settings.
The mission of NCCN is to improve the quality, effectiveness, and efficiency of cancer care so that patients can live better lives. Improving medication safety is an important aspect of fulfilling ...this mission. In September 2014, the NCCN Best Practices Committee began a medication safety initiative to improve the safe use of vincristine. This article describes and discusses this initiative.
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