Single-cell analysis of the CD8+ T-cell compartment in multiple myeloma reveals disease specific changes are chiefly restricted to a CD69- subset suggesting potent cytotoxic effectors exist within the tumor bed.

Multiple myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of Granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T cells from patients with MM more closely resembles TCR-activated CD8+ T cells from age-matched controls than their resting counterparts.

A single-day polychemotherapy regimen with proteasome inhibitor combinations for relapsed/refractory myeloma in the era of novel therapies.

PCAB (prednisone, cyclophosphamide, doxorubicin, carmustine) is a single-day regimen previously used for induction and now in relapsed/refractory multiple myeloma (RRMM). We retrospectively analysed the outcomes of 85 patients from five Australian centres. These included 30 patients (35.3%) who received PCAB with one additional agent (bortezomib most frequently). Median age of the patients was 65 years (37-80), with a median of four (1-8) prior lines of therapy. ORR was 37% (CR 4.9%). Median progression free survival and overall survival were 4.4 months (95% CI 3.5-6.7) and 7.4 months (95% CI 6.4-10.2), respectively. Extramedullary disease (EMD) was associated with shorter survival. Grade 3 or 4 cytopenia and febrile neutropenia occurred in 76.2% and 39.1%, respectively, with six (7.1%) treatment-related mortalities. Median inpatient stay was 3.3 days/28-day cycle (IQR 0.6-13), and for patients who died, a median of 20.2% of days alive were spent inpatient (IQR 6.4-39.1%). Three patients were successfully bridged to CAR T-cell therapy using PCAB, despite being penta-exposed and having EMD. PCAB may be considered as a useful salvage therapy amongst other polychemotherapy regimens in late relapse. Further studies is warranted to investigate and define its role as a bridging therapy to novel therapeutics.

Sleep dysfunction associated with worse chemotherapy-induced peripheral neurotoxicity functional outcomes.

PURPOSE: Sleep problems are commonly reported by cancer survivors; however, knowledge of the impact of chemotherapy-induced peripheral neurotoxicity (CIPN) on sleep quality remains limited. In this study, we explored the impact of CIPN on sleep quality, as well as identified clinical characteristics associated with poor sleep quality. METHODS: Participants were assessed cross-sectionally post-neurotoxic chemotherapy. CIPN severity was graded using a range of questionnaires that assessed CIPN severity and quality of life, as well as neurological grading scales. Sleep quality was assessed using a self-rated questionnaire (Pittsburgh Sleep Quality Index, PSQI). Participants with poor sleep quality were further grouped according to whether sleep impairment was due to CIPN or other factors. RESULTS: Among 77 participants who reported CIPN, 75% (n = 58) reported poor sleep quality. Of those, 41% (n = 24) reported CIPN as contributing to sleep impairment, while 59% (n = 34) reported other causes. Participants with CIPN-induced sleep impairments had higher CIPN severity across all outcome measures, as well as greater neuropathic pain (all p < 0.05). Furthermore, participants with CIPN-induced sleep impairments reported worse impact of neuropathy on physical and social functioning, as well as emotional well-being (all p < 0.05). CONCLUSIONS: Participants with CIPN-induced poor sleep quality reported worse scores across all CIPN severity measures. This emphasises the negative impacts of CIPN symptoms on quality of life of chemotherapy-treated patients and highlights the importance of sleep quality assessment in cancer survivors.

Predictors of early mortality in multiple myeloma: Results from the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR).

The frequency and causes of early mortality in patients with newly diagnosed multiple myeloma (NDMM) have not been well described in the era of novel agents. We investigated early mortality in a prospective cohort study of all patients with NDMM registered on the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) at 36 institutions between July 2011 and March 2020. Early mortality was defined as death from any cause within the first 12 months after diagnosis. A total of 2377 patients with NDMM were included in the analysis, with a median (interquartile range) age of 67.4 (58.9-74.60 years, and 60% were male. Overall, 216 (9.1%) patients died within 12 months, with 119 (4.5%) having died within 6 months. Variables that were independent predictors of early mortality after adjustment in multivariable regression included age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.05-1.08; p < 0.001), Eastern Cooperative Oncology Group performance status (OR 1.50, 95% CI 1.26-1.79; p < 0.001), serum albumin (OR 0.95, 95% CI 0.93-0.98; p < 0.001), cardiac disease (OR 1.96, 95% CI 1.35-2.86; p < 0.001) and International Staging System (OR 1.40, 95% CI 1.07-1.82; p = 0.01). For those with a primary cause of death available, it was reported as disease-related in 151 (78%), infection 13 (7%), other 29 (15%). Infection was listed as a contributing factor for death in 38% of patients.

Association of electrochemical skin conductance with neuropathy in chemotherapy-treated patients.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event of cancer treatment that can affect sensory, motor, or autonomic nerves. Assessment of autonomic neuropathy is challenging, with limited available tools. Accordingly, it is not routinely assessed in chemotherapy-treated patients. In this study, we aimed to examine whether electrochemical skin conductance (ESC) via Sudoscan, a potential measure of autonomic function, associates with subjective and objective measures of CIPN severity and autonomic neuropathy. METHODS: A cross-sectional assessment of patients who completed neurotoxic chemotherapy 3-24 months prior was undertaken using CIPN patient-reported outcomes (EORTC-QLQ-CIPN20), clinically graded scale (NCI-CTCAE), neurological examination score (TNSc), autonomic outcome measure (SAS), and Sudoscan. Differences in CIPN severity between participants with or without ESC dysfunction were investigated. Linear regression analyses were used to identify whether ESC values could predict CIPN severity. RESULTS: A total of 130 participants were assessed, with 93 participants classified with CIPN according to the clinically graded scale (NCI-CTCAE/grade ≥ 1), while 49% demonstrated hands or feet ESC dysfunction (n = 46). Participants with ESC dysfunction did not significantly differ from those with no dysfunction on multiple CIPN severity measures (clinical-grade, patient-report, neurological examination), and no differences on the autonomic outcome measure (SAS) (all p > 0.0063). Linear regression analyses showed that CIPN could not be predicted by ESC values. CONCLUSIONS: The inability of ESC values via Sudoscan to predict clinically-graded and patient-reported CIPN or autonomic dysfunction questions its clinical utility for chemotherapy-treated patients. The understanding of autonomic neuropathy with chemotherapy treatment remains limited and must be addressed to improve quality of life in cancer survivors.

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials.

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.

Balance Deficits and Functional Disability in Cancer Survivors Exposed to Neurotoxic Cancer Treatments.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) persists after treatment in up to 40% of cancer survivors and has been linked with increased balance deficits, disabilities, and fall occurrences. This study aimed to comprehensively assess the links between CIPN, balance deficits, and functional disability and to inform the development of clinical screening tools for patients at risk of these events. PATIENTS AND METHODS: A total of 190 cancer survivors exposed to neurotoxic chemotherapies (age, 57 ± 13 years; average time from completion of neurotoxic therapy, 12 ± 11 months) attended a neurology research clinic for a single cross-sectional assessment of patient-reported and objective CIPN, standing balance in 4 conditions of increasing difficulty, and functional disability. RESULTS: Most patients (68%) reported CIPN symptoms at assessment. Symptomatic patients displayed increased functional disability (F=39.4; P<.001) and balance deficits (F=34.5; P<.001), with degree of balance impairments consistent with a healthy elderly population (age ≥65 years) reporting multiple falls over the subsequent year. Increasing CIPN severity correlated with increasing functional disability (clinically assessed R2=0.46; patient-reported R2=0.49; P<.001) and balance deficits (clinically assessed R2=0.41; patient-reported R2=0.30; P<.001). A 5-factor model of key independent correlates-patient-reported numbness/tingling, weakness, and balance deficit; age; and vibration perception-was strongly linked to balance deficits (R2=0.46; P<.001) and functional disability (R2=0.56; P<.001). CONCLUSIONS: This study confirms links between increasing CIPN severity and increasing balance deficits and functional disability using comprehensive CIPN assessment methodology. The extent of balance deficits in patients with CIPN underscores the functional consequences of neurotoxicity. A 5-factor model provides a foundation for clinical screening tools to assess balance deficits and functional disability in patients exposed to neurotoxic chemotherapies.

Meeting Quality Measures for Adolescent Preventive Care: Assessing the Perspectives of Key Stakeholders.

BACKGROUND: Health plans are increasingly implementing quality improvement strategies aimed at meeting adolescent clinical quality measures, yet clinics often struggle to meet these measures. This qualitative study was conducted to explore how efforts to meet the National Committee for Quality Assurance (NCQA) Healthcare Effectiveness Data and Information Set (HEDIS) performance measure for adolescent well-care visits were perceived by a multidisciplinary group of stakeholders. METHODS: The research team conducted 26 in-depth, semistructured interviews with participants from three stakeholder groups: clinic staff with direct patient contact, health care institutional leaders, and representatives of a payer organization. Interviews were about 45 minutes in duration, audio-recorded, and professionally transcribed. Framework analysis was used to identify and organize emergent themes, and Atlas.ti was used to facilitate data management and analysis. RESULTS: Stakeholder groups diverged in their opinions regarding strategies for achieving adolescent quality measures. Stakeholders with no direct patient interaction touted transactional quality improvement strategies that directly incentivized patients and families. In contrast, clinic staff with direct patient contact believed that incentive-based efforts undermined patient-provider relationships and the clinics' focus on wellness. CONCLUSION: A considerable disconnect exists between stakeholders with and without patient contact with regard to approaches to the delivery of well care and quality improvement strategies for meeting the adolescent well-care visit performance measure. Efforts to reconcile discordant perspectives and promote a mutual understanding between payers, institutional leaders, and clinic staff could inform the development of creative initiatives that are sustainable and effective at achieving adolescent and family engagement, as well as clinical performance benchmarks.

Design and development of the Australian and New Zealand (ANZ) myeloma and related diseases registry.

BACKGROUND: Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR) was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. METHODS: The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. RESULTS: More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and 'real world' outcome data, to support the conduction of high quality studies. In addition, the Myeloma 1000 sub-study is establishing a repository of paired peripheral blood specimens from registry patients to study mechanisms underlying disease progression. CONCLUSION: Establishment of the MRDR has been challenging, but it is a valuable investment that will provide a platform for coordinated national and international collaboration for clinical research in PCD in ANZ.

Upper-limb dysfunction in cancer survivors with chemotherapy-induced peripheral neurotoxicity.

INTRODUCTION: Upper-limb symptoms are often reported in the context of chemotherapy-induced peripheral neurotoxicity (CIPN), but objective quantification of functional deficits is often lacking. We examined and compared a range of neurophysiological and functional assessments of the upper-limb in the assessment of CIPN severity. METHODS: Cross-sectional assessment of neurotoxic chemotherapy-treated patients was undertaken using patient-reported and clinically-graded CIPN measures. Upper-limb functional assessments comprised of assessing fine motor skills, sensory perception, and neurophysiological measures of the median nerve. Group comparisons between participants who reported absence or presence of upper-limb functional deficits were investigated. RESULTS: 60 participants who were 11.5 (IQR = 4.0-26.0) months post-neurotoxic chemotherapy treatment reported CIPN. 65% (n = 39) reported upper-limb CIPN symptoms. Reduction in fine motor skills, sensory perception and median nerve SNAP amplitudes were associated with higher CIPN severity. Participants who self-reported presence of upper-limb functional deficits had worse CIPN severity across all measures, compared to participants who reported no upper-limb functional deficits. CONCLUSIONS: Participants who reported upper-limb symptoms and functional deficits had worse CIPN severity and quality-of-life. There is a high burden of upper-limb dysfunction long after neurotoxic chemotherapy treatment cessation. Focus on research into supportive care and rehabilitation options to improve upper-limb function is warranted to improve patient quality-of-life.

Advanced Practice Nursing Titles and Roles in Cancer Care: A Scoping Review.

OBJECTIVES: Advanced practice nursing roles in cancer care are diverse and exist across the cancer care continuum. However, the titles used and the scope of practice differ across countries. This diversity is likely to be misleading to patients and influence nurses' contribution to health care. An understanding of the current state of advanced practice nursing roles in cancer care internationally is needed to inform opportunities for future role development and enhance cancer nursing career pathways. METHODS: This scoping review included a systematic search of four databases: MEDLINE, CINAHL, PsycINFO, and Academic Search Complete. Independent screening for papers meeting the review's inclusion criteria was undertaken using online screening software. Data extraction, coding, and mapping were undertaken in NVivo 12. RESULTS: Of the 13,409 records identified, 108 met the review's inclusion criteria. A variety of roles in cancer care settings were described. The United States and the United Kingdom had the most titles for advanced practice nursing roles. Tumor-specific roles were described and integrated into different phases of the cancer care continuum. Trends in continuing professional development for advanced practice nurses in cancer care included the rise in Fellowship programs in the United States and practice-based education in the United Kingdom. CONCLUSIONS: The differences in advanced practice nursing roles in cancer care allow regional and institutional variation to meet the needs of patient populations and health care system demands. However, a lack of clarity surrounding titles and roles results in confusion and underutilization of these nurses' highly specialized skill sets. IMPLICATIONS FOR NURSING PRACTICE: Incongruence in titles and scope of practice internationally will ultimately result in a merging of roles. There is a need for international agreement on education requirements for advanced practice nursing roles to promote career pathways.

Moving the Needle Toward Equity: What NIH Is Doing to Promote Diversity, Inclusion, and Accessibility in Research on Intellectual and Developmental Disabilities.

As a major funder of research on intellectual and developmental disabilities (IDD), NIH has a broad view of the profound impact of cultural and structural barriers on the characteristics of IDD study populations and the composition of the IDD research workforce. While long overdue, multiple efforts are currently underway across NIH aimed at addressing these barriers and increasing meaningful representation in biomedical and behavioral research.

Why Definitional Clarity Matters: Implications for the Operationalization of Emotional Well-Being.

The National Institutes of Health (NIH) is increasingly prioritizing research on health-promoting processes. Park et al. (this issue) respond to a call made by NIH to advance the study of emotional well-being (EWB) and to increase understanding of the fundamental constituents of EWB across the lifespan and among diverse subgroups. They propose a definition of EWB that provides an organizing framework for research on 'psychological aspects of well-being' and health. We commend this important first step and urge consideration of three important issues related to operationalization - the process by which an abstract concept is transformed into variables that can be measured - in future research on EWB. We expect that an iterative process of construct refinement and empirical validation will advance the study of EWB, producing scientific discoveries that can be leveraged to enhance health across the lifespan.

Morinda citrifolia (Noni) Juice Augments Mammary Gland Differentiation and Reduces Mammary Tumor Growth in Mice Expressing the Unactivated c-erbB2 Transgene.

Morinda citrifolia (noni) is reported to have many beneficial properties, including on immune, inflammatory, quality of life, and cancer endpoints, but little is known about its ability to prevent or treat breast cancer. To test its anticancer potential, the effects of Tahitian Noni Juice (TNJ) on mammary carcinogenesis were examined in MMTV-neu transgenic mice. Mammary tumor latency, incidence, multiplicity, and metastatic incidence were unaffected by TNJ treatment, which suggests that it would not increase or decrease breast cancer risk in women taking TNJ for its other benefits. However, noni may be useful to enhance treatment responses in women with existing HER2/neu breast cancer since TNJ resulted in significant reductions in tumor weight and volume and in longer tumor doubling times in mice. Remarkably, its ability to inhibit the growth of this aggressive form of cancer occurred with the mouse equivalent of a recommended dose for humans (<3 oz/day). A 30-day treatment with TNJ also induced significant changes in mammary secondary ductule branching and lobuloalveolar development, serum progesterone levels, and estrous cycling. Additional studies investigating TNJ-induced tumor growth suppression and modified reproductive responses are needed to characterize its potential as a CAM therapy for women with and without HER2(+) breast cancer.

Real-world utilisation of ASCT in multiple myeloma (MM): a report from the Australian and New Zealand myeloma and related diseases registry (MRDR).

Supported by clinical trial proven survival benefit, clinical guidelines recommend upfront autologous stem cell transplantation (ASCT) for eligible MM patients. However, reported real-world utilisation is lower than expected (40-60%). We reviewed ASCT utilisation, demographics and outcomes for MM patients (≤70 years, ≥12-month follow-up) enroled onto the Australian/New Zealand MRDR from June 2012 to May 2020. In 982 patients (<65 years: 684, 65-70 years: 298), ASCT utilisation was 76% overall (<65 years: 83%, 65-70 years: 61%, front-line therapy: 67%). Non-ASCT recipients were older (median age: 65 years vs 60 years, p < 0.001), had more comorbidities (cardiac disease: 16.9% vs 5.4%, p < 0.001; diabetes: 19.1% vs 7.0%, p < 0.001; renal dysfunction: median eGFR(ml/min): 68 vs 80, p < 0.001), inferior performance status (ECOG ≥ 2: 26% vs 13%, p < 0.001) and higher-risk MM (ISS-3: 37% vs 26%, p = 0.009, R-ISS-3 18.6% vs 11.8%, p = 0.051) than ASCT recipients. ASCT survival benefit (median progression-free survival (PFS): 45.3 months vs 35.2 months, p < 0.001; overall survival (OS): NR vs 64.0 months, p < 0.001) was maintained irrespective of age (<65 years: median PFS: 45.3 months vs 37.7 months, p = 0.04, OS: NR vs 68.2 months, p = 0.002; 65-70 years: median PFS: 46.7 months vs 29.2 months, p < 0.001, OS: 76.9 months vs 55.6 months, p = 0.005). This large, real-world cohort reaffirms ASCT survival benefit, including in 'older' patients necessitating well-designed studies evaluating ASCT in 'older' MM to inform evidence-based patient selection.

The Myeloma Landscape in Australia and New Zealand: The First 8 Years of the Myeloma and Related Diseases Registry (MRDR).

BACKGROUND: Real-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020. METHODS: We reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS). RESULTS: As of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001). CONCLUSION: Clinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context.

Virucidal efficacy of guanidine-free inactivants and rapid test buffers against SARS-CoV-2.

A pathogen inactivation step during collection or processing of clinical samples has the potential to reduce infectious risks associated with diagnostic procedures. It is essential that these inactivation methods are demonstrated to be effective, particularly for non-traditional inactivation reagents or for commercial products where the chemical composition is undisclosed. This study assessed inactivation effectiveness of twenty-four next-generation (guanidine-free) nucleic acid extraction lysis buffers and twelve rapid antigen test buffers against SARS-CoV-2, the causative agent of COVID-19. These data have significant safety implications for SARS-CoV-2 diagnostic testing and support the design and evidence-based risk assessment of these procedures.

Antibiotic resistant Klebsiella spp. from a hospital, hospital effluents and wastewater treatment plants in the uMgungundlovu District, KwaZulu-Natal, South Africa.

Hospital effluents are crucial hotspots for the dissemination of antibiotic resistant microorganisms. This study analysed hospital effluent and proximate wastewater treatment plants for the presence of antibiotic resistant Klebsiella spp. Water samples were obtained twice over a three-month period from an urban and rural hospital at three effluent points each, and from two proximate wastewater treatment plants (WWTPs) comprising influent and effluent and river water samples up/downstream the WWTPs. Presumptive Klebsiella spp. were enumerated, isolated, and phenotypically confirmed using a well-established commercial test system for Enterobacteriaceae (API20E). Clinical Klebsiella pneumoniae isolates were provided by a hospital for comparison. The antibiotic resistance profiles of Klebsiella spp. isolates to 16 selected antibiotics were established according to EUCAST (European Committee on Antimicrobial Susceptibility Testing). In addition, extended spectrum ß-lactamase (ESBL) and carbapenemase production was analysed. A total of 93 confirmed Klebsiella spp. isolates from hospital effluents and 37 from WWTPs were obtained, comprising K. pneumoniae and K. oxytoca. The viable counts for confirmed Klebsiella spp. for hospital effluents ranged from 1.38 × 102 to 1.03 × 104, while those for WWTP influent were in a range of 1.76 × 103 to 5.10 × 103 CFU/ml. A higher proportion of Klebsiella spp. from urban hospital effluent was categorized as multidrug-resistant (MDR) (23%) compared to rural hospital effluent (9%). Resistance was observed to all antibiotic classes tested. Several clinical isolates presented resistance to four carbapenem antibiotics, while certain isolates from hospital effluent and WWTPs exhibited ertapenem and doripenem resistance. Fifteen Klebsiella spp. isolates (clinical and from urban hospital effluent) produced carbapenemases. Hospital effluents in South Africa contain antibiotic resistant Klebsiella spp. and may pose a risk to proximate informal communities if inadequately treated. Moreover, common phenotypic resistance profiles among isolates from the clinical-hospital effluent-wastewater works continuum suggest a need for further treatment of such effluent.

Communication between neonatologists and parents when prognosis is uncertain.

OBJECTIVE: When an infant's prognosis is uncertain, communication between neonatologists and parents surrounding goals of care and decision-making can be challenging. This qualitative study explored communication between neonatologists and parents to discover qualities which may enhance or impede parent-clinician partnership under such difficult circumstances. STUDY DESIGN: Guided by the National Cancer Institute (NCI) Patient Centered Communication framework, semi-structured individual interviews were conducted and analyzed regarding neonatologist and parent perceptions of their communication. Subjects consisted of nine dyads of neonatologists and English-speaking parents whose infant had an uncertain prognosis. RESULTS: Parents were overall satisfied with neonatologists' communications concerning their infant's uncertain trajectory. Nonetheless, both experienced challenges and distress during communication, impeding collaboration and engagement. CONCLUSIONS: Families and neonatologists value principles of patient centered communication but report challenges implementing this practice. Incorporating a multidisciplinary approach in settings of prognostic uncertainty to foster patient centered communication, may enhance communication surrounding NICU care.