Chloramphenicol versus ceftriaxone for the treatment of pneumonia and sepsis in elderly patients with advanced dementia and functional disability. A propensity-weighted retrospective cohort study.

BACKGROUND: Sepsis and pneumonia in the elderly comprise a significant portion of medical admissions. Chloramphenicol has been used in Israel for treatment of bacterial infections, without evidence regarding its efficacy and safety. OBJECTIVES: We aimed to examine whether chloramphenicol was associated with similar outcomes to ceftriaxone, for treatment of sepsis and pneumonia in the elderly with dementia and functional disability. METHODS: Patients over 75, with dementia and functional disability, admitted to the internal medicine ward at Beilinson Hospital between 2011 and 2021, with community-acquired aspiration pneumonia or sepsis of undetermined source were included. Patients with mild dementia and independent in their activities of daily living were excluded. Primary outcome was 30- and 90-day all-cause mortality. A propensity-weighted multivariable model was constructed using inverse probability of treatment weighting. Results were expressed as OR with 95% CI. RESULTS: In total, 1558 patients were included: 512 treated with chloramphenicol and 1046 with ceftriaxone. The cohort consisted of elderly patients (mean age 87 ±â€Š6.2 years) with comorbidities; 30- and 90-day all-cause mortality were similar [222/512 (43.3%) versus 439/1046 (41.9%) P = 0.602, and 261/512 (50.9%) versus 556/1046 (53.1%) P = 0.419, respectively]. Propensity-weighted, logistic multivariable analysis for 30- and 90-day all-cause mortality revealed similar mortality rates for chloramphenicol and ceftriaxone (OR 1.049 95% CI 0.217-1.158, OR 0.923 95% CI 0.734-1.112, respectively). CONCLUSION: In this retrospective cohort of elderly debilitated patients hospitalized with pneumonia and sepsis, we found no difference in 30- and 90-day mortality between those treated with chloramphenicol or ceftriaxone. Further studies should determine the efficacy and safety of chloramphenicol in this population.

Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study.

Study objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.

Ricinus communis-linn (castor plant), male contraceptives and reproductive health of women.

The medicinal use of castor plant is extensive. Castor oil is most commonly used as a laxative, and the leaves and seeds have been used to augment labour, promote lactation and to treat syphilis and leprosy. Its use for contraception is an ancient practice among the Rukuba women of Plateau State in Nigeria, who would chew 2-3 seeds for contraceptive coverage of one year. The acute and chronic spermatogenic effect of the minor seed variety of ricinus communis-linn is hereby reported. Thirty male rats weighing 200-250g were grouped (n = 5) and treated with the n-hexane extract of the seeds, each made up to 1ml with physiological saline, and given as a single dose, intraperitoneally. Control groups had 1 ml physiological saline. Semen was collected 72 h and 6 weeks after treatment and analyzed within one hour of collection. The seed extract suppressed spermatogenesis and sperm motility up to six weeks after treatment. But semen parameters reverted to normal values in the 7 weeks of treatment, showing primary spermatocytes and spermatids in the seminiferous tubules. Our results showed ricinus communis-linn to be a potent but reversible anti-spermatogenic agent with significant anti-motility properties. Moreover, being of plant origin, it is readily available and affordable. We hereby present ricinus communis-linn as a possible male contraceptive agent that can relieve women of their reproductive burden globally.

Measurement of Backaction from Electron Spins in a Gate-Defined GaAs Double Quantum dot Coupled to a Mesoscopic Nuclear Spin Bath.

Decoherence of a quantum system arising from its interaction with an environment is a key concept for understanding the transition between the quantum and classical world as well as performance limitations in quantum technology applications. The effects of large, weakly coupled environments are often described as a classical, fluctuating field whose dynamics is unaffected by the qubit, whereas a fully quantum description still implies some backaction from the qubit on the environment. Here we show direct experimental evidence for such a backaction for an electron-spin qubit in a GaAs quantum dot coupled to a mesoscopic environment of order 10^{6} nuclear spins. By means of a correlation measurement technique, we detect the backaction of a single qubit-environment interaction whose duration is comparable to the qubit's coherence time, even in such a large system. We repeatedly let the qubit interact with the spin bath and measure its state. Between such cycles, the qubit is reinitialized to different states. The correlations of the measurement outcomes are strongly affected by the intermediate qubit state, which reveals the action of a single electron spin on the nuclear spins.

Parity-Protected Superconductor-Semiconductor Qubit.

Coherence of superconducting qubits can be improved by implementing designs that protect the parity of Cooper pairs on superconducting islands. Here, we introduce a parity-protected qubit based on voltage-controlled semiconductor nanowire Josephson junctions, taking advantage of the higher harmonic content in the energy-phase relation of few-channel junctions. A symmetric interferometer formed by two such junctions, gate-tuned into balance and frustrated by a half-quantum of applied flux, yields a cos(2φ) Josephson element, reflecting coherent transport of pairs of Cooper pairs. We demonstrate that relaxation of the qubit can be suppressed tenfold by tuning into the protected regime.

Implementation and dissemination of an African American popular opinion model to improve lupus awareness: an academic-community partnership.

OBJECTIVE: Lupus is a chronic, autoimmune disease that disproportionately affects African Americans. We adapted the Centers for Disease Control and Prevention's Popular Opinion Leader model to implement an intervention tailored for African American individuals that leverages an academic-community partnership and community-based social networks to disseminate culturally appropriate lupus education. METHODS: Academic rheumatologists, social scientists, and researchers in Boston, MA and Chicago, IL partnered with local lupus support groups, community organizations, and churches in neighborhoods with higher proportions of African Americans to develop curriculum and recruit community leaders with and without lupus (Popular Opinion Leaders; POLs). POLs attended four training sessions focused on lupus education, strategies to educate others, and a review of research methods. POLs disseminated information through their social networks and recorded their impact, which was mapped using a geographic information system framework. RESULTS: We trained 18 POLs in greater Boston and 19 in greater Chicago: 97% were African American, 97% were female; and the mean age was 57 years. Fifty-nine percent of Boston POLs and 68% of Chicago POLs had lupus. POLs at both sites engaged members of their social networks and communities in conversations about lupus, health disparities, and the importance of care. Boston POLs documented 97 encounters with 547 community members reached. Chicago POLs documented 124 encounters with 4083 community members reached. CONCLUSIONS: An adapted, community-based POL model can be used to disseminate lupus education and increase awareness in African American communities. Further research is needed to determine the degree to which this may begin to reduce disparities in access to care and outcomes.

"Just too busy living in the moment and surviving": barriers to accessing health care for structurally vulnerable populations at end-of-life.

BACKGROUND: Despite access to quality care at the end-of-life (EOL) being considered a human right, it is not equitable, with many facing significant barriers. Most research examines access to EOL care for homogenous 'normative' populations, and as a result, the experiences of those with differing social positioning remain unheard. For example, populations experiencing structural vulnerability, who are situated along the lower rungs of social hierarchies of power (e.g., poor, homeless) will have unique EOL care needs and face unique barriers when accessing care. However, little research examines these barriers for people experiencing life-limiting illnesses and structural vulnerabilities. The purpose of this study was to identify barriers to accessing care among structurally vulnerable people at EOL. METHODS: Ethnography informed by the critical theoretical perspectives of equity and social justice was employed. This research drew on 30 months of ethnographic data collection (i.e., observations, interviews) with structurally vulnerable people, their support persons, and service providers. Three hundred hours of observation were conducted in homes, shelters, transitional housing units, community-based service centres, on the street, and at health care appointments. The constant comparative method was used with data collection and analysis occurring concurrently. RESULTS: Five significant barriers to accessing care at EOL were identified, namely: (1) The survival imperative; (2) The normalization of dying; (3) The problem of identification; (4) Professional risk and safety management; and (5) The cracks of a 'silo-ed' care system. Together, findings unveil inequities in accessing care at EOL and emphasize how those who do not fit the 'normative' palliative-patient population type, for whom palliative care programs and policies are currently built, face significant access barriers. CONCLUSIONS: Findings contribute a nuanced understanding of the needs of and barriers experienced by those who are both structurally vulnerable and facing a life-limiting illness. Such insights make visible gaps in service provision and provide information for service providers, and policy decision-makers alike, on ways to enhance the equitable provision of EOL care for all populations.

Developmentally appropriate care for adolescents and young adults with cancer: how well is Australia doing?

PURPOSE: Developmentally appropriate care underpins quality cancer treatment. This study aimed to describe how well Australian cancer services deliver patient-focussed, developmentally appropriate care to adolescents and young adults (AYAs) with cancer. METHODS: In a national, cross sectional study, 196 AYAs with cancer aged between 15 and 25 years at diagnosis reported their general experiences of the cancer care team (Cancer Needs Questionnaire), access to age-appropriate treatment environments (Cancer Needs Questionnaire) and frequency of psychosocial assessment (Adolescent Friendly Hospital Survey). RESULTS: Very positive responses were reported around engagement and communication with staff who were reported as approachable, friendly and trustworthy; 11 of the 14 items were positively rated by over 90% of respondents. In contrast, over 70% of AYAs expressed unmet need around their physical and social environments, whether in relation to the opportunity to be nursed in wards designed for AYAs, spend time with other young people with cancer, or talk to young people their own age; less than a third reported their needs had been met on the majority of these items. The frequency that specific psychosocial assessment domains were discussed was highly variable; responses suggested that AYAs were less commonly questioned about overtly sensitive topics. AYAs who experienced private consultations with health care providers (41%) were significantly more likely to experience thorough psychosocial assessment. CONCLUSION: Australian cancer services are generally communicating well with AYAs. There is room for improvement around more developmentally specific aspects of healthcare quality, such as psychosocial assessment, and around treatment environments that promote greater social interaction between AYAs.

Risk factors for biopsy-proven advanced non-alcoholic fatty liver disease in the Veterans Health Administration.

BACKGROUND: With its increasing incidence, nonalcoholic fatty liver disease (NAFLD) is of particular concern in the Veterans Health Administration (VHA). AIMS: To evaluate risk factors for advanced fibrosis in biopsy-proven NAFLD in the VHA, to identify patients at risk for adverse outcomes. METHODS: In randomly selected cases from VHA databases (2005-2015), we performed a retrospective case-control study in adults with biopsy-defined NAFLD or normal liver. RESULTS: Of 2091 patients reviewed, 399 met inclusion criteria. Normal controls (n = 65) had normal liver function. The four NAFLD cohorts included: NAFL steatosis (n = 76), nonalcoholic steatohepatitis (NASH) without fibrosis (n = 68), NAFLD/NASH stage 1-3 fibrosis (n = 82), and NAFLD/NASH cirrhosis (n = 70). NAFLD with hepatocellular carcinoma (HCC) was separately identified (n = 38). Most patients were older White men. NAFLD patients with any fibrosis were on average severely obese (BMI>35 kg/m2 ). Diabetes (54.4%-79.6%) and hypertension (85.8%-100%) were more common in NAFLD with fibrosis or HCC. Across NAFLD, 12.3%-19.5% were enrolled in diet/exercise programs and 0%-2.6% had bariatric surgery. Hispanics exhibited higher rates of NASH (20.6%), while Blacks had low NAFLD rates (1.4%-11.8%), particularly NAFLD cirrhosis and HCC (1.4%-2.6%). Diabetes (OR 11.8, P < .001) and BMI (OR 1.4, P < .001) were the most significant predictors of advanced fibrosis. CONCLUSIONS: In the VHA, diabetes and severe obesity increased risk for advanced fibrosis in NAFLD. Of these patients, only a small proportion (~20%) had enrolled in diet/exercise programs or had bariatric surgery (~2%). These results suggest that providers should focus/tailor interventions to improve outcomes, particularly in those with diabetes and severe obesity.

Barriers and facilitators to implementing addiction medicine fellowships: a qualitative study with fellows, medical students, residents and preceptors.

BACKGROUND: Although progress in science has driven advances in addiction medicine, this subject has not been adequately taught to medical trainees and physicians. As a result, there has been poor integration of evidence-based practices in addiction medicine into physician training which has impeded addiction treatment and care. Recently, a number of training initiatives have emerged internationally, including the addiction medicine fellowships in Vancouver, Canada. This study was undertaken to examine barriers and facilitators of implementing addiction medicine fellowships. METHODS: We interviewed trainees and faculty from clinical and research training programmes in addiction medicine at St Paul's Hospital in Vancouver, Canada (N = 26) about barriers and facilitators to implementation of physician training in addiction medicine. We included medical students, residents, fellows and supervising physicians from a variety of specialities. We analysed interview transcripts thematically by using NVivo software. RESULTS: We identified six domains relating to training implementation: (1) organisational, (2) structural, (3) teacher, (4) learner, (5) patient and (6) community related variables either hindered or fostered addiction medicine education, depending on context. Human resources, variety of rotations, peer support and mentoring fostered implementation of addiction training. Money, time and space limitations hindered implementation. Participant accounts underscored how faculty and staff facilitated the implementation of both the clinical and the research training. CONCLUSIONS: Implementation of addiction medicine fellowships appears feasible, although a number of barriers exist. Research into factors within the local/practice environment that shape delivery of education to ensure consistent and quality education scale-up is a priority.

Two birds with one stone: experiences of combining clinical and research training in addiction medicine.

BACKGROUND: Despite a large evidence-base upon which to base clinical practice, most health systems have not combined the training of healthcare providers in addiction medicine and research. As such, addiction care is often lacking, or not based on evidence or best practices. We undertook a qualitative study to assess the experiences of physicians who completed a clinician-scientist training programme in addiction medicine within a hospital setting. METHODS: We interviewed physicians from the St. Paul's Hospital Goldcorp Addiction Medicine Fellowship and learners from the hospital's academic Addiction Medicine Consult Team in Vancouver, Canada (N = 26). They included psychiatrists, internal medicine and family medicine physicians, faculty, mentors, medical students and residents. All received both addiction medicine and research training. Drawing on Kirkpatrick's model of evaluating training programmes, we analysed the interviews thematically using qualitative data analysis software (Nvivo 10). RESULTS: We identified five themes relating to learning experience that were influential: (i) attitude, (ii) knowledge, (iii) skill, (iv) behaviour and (v) patient outcome. The presence of a supportive learning environment, flexibility in time lines, highly structured rotations, and clear guidance regarding development of research products facilitated clinician-scientist training. Competing priorities, including clinical and family responsibilities, hindered training. CONCLUSIONS: Combined training in addiction medicine and research is feasible and acceptable for current doctors and physicians in training. However, there are important barriers to overcome and improved understanding of the experience of addiction physicians in the clinician-scientist track is required to improve curricula and research productivity.

An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic.

BACKGROUND: People living with HIV (PLHIV) who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC) is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. METHODS: Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA) study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76) and non-DPC clients (n = 482) with a history of injection drug use. RESULTS: Of the 917 LISA participants included within this analysis, 100 (10.9%) reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09-8.37); use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79-5.61); to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12-3.99); to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23-6.19); and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38-4.15). CONCLUSIONS: Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced by PLHIV with a history of injection drug use living within urban centres in North America and beyond.

Meaningful engagement of people living with HIV who use drugs: methodology for the design of a Peer Research Associate (PRA) hiring model.

BACKGROUND: Community-based HIV, harm reduction, and addiction research increasingly involve members of affected communities as Peer Research Associates (PRAs)-individuals with common experiences to the participant population (e.g. people who use drugs, people living with HIV [PLHIV]). However, there is a paucity of literature detailing the operationalization of PRA hiring and thus limited understanding regarding how affected communities can be meaningfully involved through low-barrier engagement in paid positions within community-based participatory research (CBPR) projects. We aim to address this gap by describing a low-threshold PRA hiring process. RESULTS: In 2012, the BC Centre for Excellence in HIV/AIDS and the Dr. Peter AIDS Foundation collaborated to develop a mixed-method CBPR project evaluating the effectiveness of the Dr. Peter Centre (DPC)-an integrative HIV care facility in Vancouver, Canada. A primary objective of the study was to assess the impact of DPC services among clients who have a history of illicit drug use. In keeping with CBPR principles, affected populations, community-based organizations, and key stakeholders guided the development and dissemination of a low-barrier PRA hiring process to meaningfully engage affected communities (e.g. PLHIV who have a history of illicit drug use) in all aspects of the research project. The hiring model was implemented in a number of stages, including (1) the establishment of a hiring team; (2) the development and dissemination of the job posting; (3) interviewing applicants; and (4) the selection of participants. The hiring model presented in this paper demonstrates the benefits of hiring vulnerable PLHIV who use drugs as PRAs in community-based research. CONCLUSIONS: The provision of low-barrier access to meaningful research employment described herein attempts to engage affected communities beyond tokenistic involvement in research. Our hiring model was successful at engaging five PRAs over a 2-year period and fostered opportunities for future paid employment or volunteer opportunities through ongoing collaboration between PRAs and a diverse range of stakeholders working in HIV/AIDS and addictions. Additionally, this model has the potential to be used across a range of studies and community-based settings interested in meaningfully engaging communities in all stages of the research process.

On-demand single-electron transfer between distant quantum dots.

Single-electron circuits of the future, consisting of a network of quantum dots, will require a mechanism to transport electrons from one functional part of the circuit to another. For example, in a quantum computer decoherence and circuit complexity can be reduced by separating quantum bit (qubit) manipulation from measurement and by providing a means of transporting electrons between the corresponding parts of the circuit. Highly controlled tunnelling between neighbouring dots has been demonstrated, and our ability to manipulate electrons in single- and double-dot systems is improving rapidly. For distances greater than a few hundred nanometres, neither free propagation nor tunnelling is viable while maintaining confinement of single electrons. Here we show how a single electron may be captured in a surface acoustic wave minimum and transferred from one quantum dot to a second, unoccupied, dot along a long, empty channel. The transfer direction may be reversed and the same electron moved back and forth more than sixty times-a cumulative distance of 0.25 mm-without error. Such on-chip transfer extends communication between quantum dots to a range that may allow the integration of discrete quantum information processing components and devices.

Clinical outcomes after a diagnosis of brain metastases in patients with estrogen- and/or human epidermal growth factor receptor 2-positive versus triple-negative breast cancer.

BACKGROUND: Women with triple-negative (TN) breast cancer are at increased risk of distant metastases and have reduced survival versus other breast cancer patients. Relative survival of women with TN breast cancer who develop brain metastases is unknown. METHODS: Patients with breast cancer who developed brain metastases at our institution from 1993 to 2006 were reviewed. Four survival time intervals were compared in patients with TN disease and those with non-TN disease: initial diagnosis to distant metastases, distant metastases to brain metastases, brain metastases to death, and overall diagnosis to death. RESULTS: One hundred and eighteen patients were identified. Fifty-one (50%) of 103 were estrogen receptor positive, 26 (39%) of 67 were human epidermal growth factor receptor 2 positive, and 20 (22%) of 91 were TN. Survival times were shorter for TN patients, with overall survival of 26 months in TN patients versus 49 months for non-TN patients. In TN patients, time to development of distant metastases, brain metastases, and death after brain metastases was shorter than in non-TN patients. CONCLUSION: Patients with TN disease were more likely to develop distant metastases earlier than non-TN patients, developed brain metastases sooner, and had shorter overall survival.

Comparing the retinal structures and functions in two species of gulls (Larus delawarensis and Larus modestus) with significant nocturnal behaviours.

Ring-billed gulls (Larus delawarensis) and gray gulls (Larus modestus) are two species active both by day and night. We have investigated the retinal adaptations that allow the diurnal and nocturnal behaviours of these two species. Electroretinograms and histological analyses show that both species have a duplex retina in which cones outnumber rods, but the number of rods appears sufficient to provide vision at night. Their retinas respond over the same scotopic dynamic range of 3.4logcdm(-2), which encompasses all of the light levels occurring at night in their photic environment. The amplitudes of the scotopic saturated a- and b-wave responses as well as the photopic saturated b-wave response and the photopic sensitivity parameter S are however higher in ring-billed gulls than in gray gulls. Moreover, the process of dark adaptation is about 30min faster in gray gulls than in ring-billed gulls. Our results suggest that both species have acquired in the course of their evolution functional adaptations that can be related to their specific photic environment.

Comparison of the retinal structure and function in four bird species as a function of the time they start singing in the morning.

We postulated that the retinas of bird species that are the earlier singers are more sensitive to low light conditions than species that sing closer to sunrise. The selected species were the American Robin (Turdus migratorius) and the Hermit Thrush (Catharus guttatus) as early singers, the Common Grackle (Quiscalus quiscula) and the Mourning Dove (Zenaida macroura) which join the dawn chorus near sunrise. Scotopic electroretinogram (ERGs) intensity-response functions were obtained from anesthetized birds, following which the animals were euthanized and their retinas processed for histological analysis. Based on k values, generally considered an adequate measurement of the scotopic (rod) retinal sensitivity, all species yielded comparable night vision capabilities. However, based on the maximal (mixed rod-cone response) amplitude of the scotopic b-wave, our results indicate that robins and thrushes yield larger scotopic ERGs compared with doves and grackles, but unexpectedly do not have higher rod:cone ratios. Increased thickness of the retinal inner nuclear layer and higher numbers of ganglion cells in robins and thrushes compared with doves and grackles suggest a greater number of synaptic connections maximizing vision under low light conditions, and might support their higher retinal responses under scotopic conditions. The higher ERG V(max) of robins and thrushes might also be explained, at least in part, by the optics (i.e., their lower minimum F-numbers), resulting in brighter retinal images, rather than from higher sensitivity of their retina. Our results suggest that an early onset of dawn singing might be correlated with the retinal ability to detect the first dim crepuscular lights.