Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts; however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4+ and CD8+ T cells, nadir CD4+ count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197 PWH with median age of 42 years, using a 56-gene panel. Seventy-nine percent had a CD4+ nadir below 200 cells/µL, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8+ T cells and nadir CD4+ counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of patients 35 years of age and older. Inflammatory biomarkers were higher in CH carriers compared with noncarriers, supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4+ and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Patient preferences in the treatment of stage III/IV classic Hodgkin lymphoma: Results from the CONNECT cross-sectional survey.

We explored patient front-line treatment preferences in newly diagnosed stage III/IV classic Hodgkin lymphoma (cHL). The CONNECT patient survey, administered online from 30 December 2020 to 1 March 2021, examined preferences overall and by age at diagnosis in 182 adult patients diagnosed with stage III/IV cHL within the past 10 years in the United States. At diagnosis, patients' median age was 36 years; 66% of patients were younger (aged 16-41 years) and 34% older (aged 42-85 years). When asked about initial treatment goals, 74% of patients ranked cure as their first or second goal (86% younger vs. 52% older patients; p < 0.001). At diagnosis, 72% of patients preferred aggressive treatment, and 85% were willing to accept more short-term risks in exchange for a better-working therapy long term. For long-term risks, younger versus older patients were significantly more concerned about second cancers (p < 0.001) and fertility issues (p = 0.007), whereas older patients were more concerned about lung damage (p = 0.028) and infections (p < 0.001). Most patients (94%) reported having a caregiver at some point, but 99% of these patients retained some control of treatment decisions. Collectively, these survey results highlight patient treatment preferences and differences in treatment goals and long-term side effect concerns based on patient age.

Physician frontline treatment preferences for stage III/IV classic Hodgkin lymphoma: the real-world US CONNECT study.

Aim: To understand US physicians' frontline (1L) treatment preferences/decision-making for stage III/IV classic Hodgkin lymphoma (cHL). Materials & methods: Medical oncologists and/or hematologists (≥2 years' practice experience) who treat adults with stage III/IV cHL were surveyed online (October-November 2020). Results: Participants (n = 301) most commonly considered trial efficacy/safety data and national guidelines when selecting 1L cHL treatments. Most physicians (91%) rated overall survival (OS) as the most essential attribute when selecting 1L treatment. Variability was seen among regimen selection for hypothetical newly diagnosed patients, with OS cited as the most common reason for regimen selection. Conclusion: While treatment selection varied based on patient characteristics, US physicians consistently cited OS as the top factor considered when selecting a 1L treatment for cHL.

Classic Hodgkin lymphoma (cHL) is a type of cancer that grows in lymph nodes. The researchers created a survey to assess how doctors in the USA choose medicine to treat patients who are newly diagnosed with an advanced stage of cHL (stage 3 or 4 out of 4 stages). We surveyed 301 doctors who treat patients with cHL. When choosing a medicine to treat cHL, most doctors said they consider results from research studies, how well the medicine works, information on the medicine's safety and recommendations in official guidelines. Most doctors said that overall survival (how long the patient survives after being diagnosed with cHL) is the most important outcome they consider when choosing a medicine to treat cHL. During the survey, doctors saw four unique patient profiles. These profiles differed in age, disease stage (how far along the cHL is) and other illnesses the patient has. While medicine choice was different across profiles, overall survival was still the reason for choosing each individual patient's medicine. These survey results show that doctors in the USA highly consider overall survival when choosing medicine for patients newly diagnosed with an advanced stage of cHL.

Real-World Treatment Patterns and Clinical Outcomes With Brentuximab Vedotin or Other Standard Therapies in Patients With Previously Treated Cutaneous T-Cell Lymphoma in the United States.

INTRODUCTION/BACKGROUND: Primary cutaneous anaplastic large-cell lymphomas (pcALCLs) are a type of cutaneous T-cell lymphoma (CTCL) in which CD30 is uniformly expressed. In mycosis fungoides (MF), another CTCL, CD30 is heterogeneously expressed. In ALCANZA, patients with pcALCLs or CD30-positive MF randomized to brentuximab vedotin (BV) vs. physician's choice of methotrexate or bexarotene had significantly improved outcomes, including higher objective response rates (ORR) lasting ≥4 months (ORR4), as well as longer median progression-free survival (PFS) and time to next treatment (TTNT). In this study, we sought to assess the real-world impact of treatment with BV in second or later lines of therapy for CTCL. MATERIALS AND METHODS: This retrospective chart review describes patient characteristics, treatment patterns, clinical outcomes, and healthcare resource use (HRU) in patients with pcALCLs or MF previously treated with ≥1 systemic therapy and subsequently treated with BV (n = 139) or other standard therapy (OST; n = 164). RESULTS: Most patients in the BV cohort (96.4%) received BV as second-line (2L) systemic therapy. The most common OSTs were methotrexate (11.6%), mogamulizumab (9.1%), and bendamustine (9.1%) monotherapies. For 2L BV and OST, median duration of therapy was 8.4 and 5.2 months, real-world ORR was 82.1% and 66.5%, and real-world ORR4 was 42.5% and 25.0%. Real-world 1- and 2-year PFS, TTNT, and OS were significantly longer (all P < .01) and HRU was lower for BV vs. OST. CONCLUSION: These real-world outcomes are consistent with ALCANZA results, demonstrating favorable outcomes with BV vs. OST in patients with CTCL previously treated with ≥1 systemic therapy.

Resistance gene-guided genome mining reveals the roseopurpurins as inhibitors of cyclin-dependent kinases.

With the significant increase in the availability of microbial genome sequences in recent years, resistance gene-guided genome mining has emerged as a powerful approach for identifying natural products with specific bioactivities. Here, we present the use of this approach to reveal the roseopurpurins as potent inhibitors of cyclin-dependent kinases (CDKs), a class of cell cycle regulators implicated in multiple cancers. We identified a biosynthetic gene cluster (BGC) with a putative resistance gene with homology to human CDK2. Using targeted gene disruption and transcription factor overexpression in Aspergillus uvarum, and heterologous expression of the BGC in Aspergillus nidulans, we demonstrated that roseopurpurin C (1) is produced by this cluster and characterized its biosynthesis. We determined the potency, specificity, and mechanism of action of 1 as well as multiple intermediates and shunt products produced from the BGC. We show that 1 inhibits human CDK2 with a Kiapp of 44 nM, demonstrates selectivity for clinically relevant members of the CDK family, and induces G1 cell cycle arrest in HCT116 cells. Structural analysis of 1 complexed with CDK2 revealed the molecular basis of ATP-competitive inhibition.

The impact of classic Hodgkin lymphoma on informal caregivers: results from the CONNECT cross-sectional survey.

PURPOSE: As part of the CONNECT study, we evaluated the caregiver role in treatment decision-making when caring for patients with classic Hodgkin lymphoma (cHL) in the USA. METHODS: The CONNECT caregiver survey was administered online December 2020-March 2021 to self-identified adult caregivers of cHL patients recruited from patient referrals and online panels. The caregiver's role in treatment decision-making, health-related quality of life (HRQoL, PROMIS-Global), and work impacts (WPAI:CG) were assessed. RESULTS: We surveyed 209 caregivers (58% women; median age 47 years; 54% employed; 53% spouse/partner); 69% of patients cared for were diagnosed with cHL in the past 1-2 years, with 48% having stage III/IV cHL and 29% in remission. More spouse/partner than other caregivers were involved in caregiving at symptom onset (61% vs 27%), whereas more other than spouse/partner caregivers began after first treatment (34% vs 5%). Cure, caregivers' top treatment goal (49%), was rated higher by spouse/partner than other caregivers (56% vs 42%). More spouse/partner than other caregivers were involved in treatment option discussions with physicians (52% vs 28%), were involved in patients' treatment decisions (54% vs 23%), and were aligned with patients' treatment goals (93% vs 79%). While caregivers reported HRQoL similar to that of the general population, nearly 30% of employed caregivers reported work impairment. CONCLUSION: Cure was caregivers' top treatment goal. Spouse/partner vs other caregivers were more involved, were involved earlier, and reported greater alignment with patient treatment goals and decision-making. Caregivers reported good HRQoL; however, caregiving impacted work productivity regardless of patient relationship.

Estimated impact of ECHELON-1 overall survival on productivity costs in stage III/IV classical Hodgkin lymphoma in the United States.

BACKGROUND: A 2010 study on the impact of cancer mortality on productivity costs found Hodgkin lymphoma to have the second largest productivity cost lost per death in the United States. The ECHELON-1 trial demonstrated that frontline brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) improves overall survival (OS) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in stage III/IV classical Hodgkin lymphoma (cHL), reducing the risk of death to 41% (hazard ratio = 0.59; 95% CI = 0.40-0.88; P = 0.009). OBJECTIVES: To assess the estimated impact of frontline treatment choice on mortality and productivity using an oncology simulation model informed by ECHELON-1 data. METHODS: Individual productivity was estimated using the human capital approach and reported via present value lifetime earnings (PVLE) estimates. Deaths avoided and lifeyears saved without and with A+AVD were calculated using a model informed by realworld treatment use, treatment-specific OS, and expert clinicians' opinions. A+AVD use in the base case was 27% (range: 0%-80%). Stage III/IV cHL prevalence over a 10-year period was estimated; downstream lifetime productivity costs were projected without and with A+AVD. RESULTS: In 2031, 3,645 patients were estimated to be newly diagnosed with stage III/IV cHL. Over 10 years with 27% A+AVD vs no A+AVD use, estimates predicted 14% fewer deaths (2,290 vs 2,650) and 14% less total PVLE losses ($1.438 vs $1.664 billion). Results from scenario analyses (40%-80% vs no A+AVD use) showed 20% to 32% decreases in PVLE losses ($1.331-$1.137 billion vs $1.664 billion), saving up to $527 million over 10 years. CONCLUSIONS: Productivity cost losses due to mortality in stage III/IV cHL are high. Increasing A+AVD use for patients with stage III/IV cHL would reduce productivity cost losses as deaths are avoided, based on ECHELON-1 OS results.

Real-World Use of Positron Emission Tomography-Computed Tomography and Reported Deauville Scores in Advanced-Stage Classic Hodgkin Lymphoma: A Community Oncology Practice Perspective.

PURPOSE: To evaluate the use of interim positron emission tomography-computed tomography (PET-CT) scans and Deauville 5-point scale (5PS) score reporting for stage III/IV classic Hodgkin lymphoma (cHL) treated frontline (1L) in community oncology settings. METHODS: This retrospective, observational study included adults with stage III/IV cHL initiating 1L doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine, or an escalated dosing regimen of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone within the US Oncology Network between January 2017 and October 2019. Data were collected from electronic health records and chart reviews and summarized descriptively. RESULTS: A total of 262 patients were included; 48.9% were age 39 years or younger. Most were male (57%), White (59%), had an International Prognostic Score <4 (76%), and received 1L ABVD (74%). Forty-nine percent of patients had stage III and 51% had stage IV cHL. Of 258 patients with ≥1 PET-CT scan, 71% (n = 184) had an interim scan and 64% received ≥1 scan at an off-site location. Of patients treated 1L with ABVD who received a baseline and interim scan, Deauville 5PS scores were not documented for 45% of patients; in 90% of these cases, a standardized uptake value (SUV) was reported. CONCLUSION: In community oncology settings, under-reporting of Deauville 5PS scores for interim PET-CT scans was observed. In the absence of Deauville 5PS scores, SUV results were generally provided. These results highlight educational opportunities that exist for PET-adapted ABVD, including consistency in reporting/utilization of Deauville 5PS scores to de-escalate or escalate treatment.

Estimating long-term outcomes in classic Hodgkin lymphoma: a United States population-based oncology simulation model based on overall survival from the ECHELON-1 trial.

The six-year ECHELON-1 update showed a survival advantage for frontline (1 L) A + AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage III/IV classic Hodgkin lymphoma (cHL). As clinical trials have limited ability to track patients for extended periods, we developed an oncology simulation model using ECHELON-1 data to estimate population-based cHL outcomes in the US over 10 years (through 2031). The model included a scenario without (64.5% ABVD, 35.5% PET-adapted ABVD utilization) and scenarios with 1 L A + AVD (27%-80%k utilization). At 27%-80% A + AVD utilization, the model estimated 13.6%-31.7% fewer deaths, 2.4%-6.3% more patients ≥5 years progression free, 9.4%-24.4% fewer stem cell transplants (SCTs), and 7.8%-22.5% fewer second cancers over 10 years. These results suggest that the improved outcomes observed in the ECHELON-1 update with A + AVD vs ABVD may translate to more patients alive and fewer with primary relapsed/refractory cHL, SCTs, and second cancers.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes for Patients With Stage III or IV Classic Hodgkin Lymphoma Treated With Frontline ABVD: A Retrospective Database Review in the United States.

In newly diagnosed stage III/IV classic Hodgkin lymphoma (cHL), A+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) improved overall survival (OS) versus ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). As clinical trial and real-world populations may differ, real-world treatment characteristics and OS (rwOS) were assessed for patients with stage III/IV cHL treated with frontline ABVD. This retrospective, observational analysis of deidentified electronic health record data (1/1/2011-8/31/2020) evaluated baseline disease and clinical characteristics, treatment patterns, and rwOS in patients with stage III/IV cHL treated with frontline ABVD. Data for 167 patients were analyzed. A median of 6 ABVD cycles were received. Baseline/interim positron emission tomography (PET) scans were obtained for 60.5%/89.8% of patients. Of patients diagnosed in 2016 or later (n = 73), 89% received an interim PET scan; 15/46 patients with no documented Deauville score, 6/15 with a score of 1 to 3, and 3/4 with a score of 4 to 5 de-escalated to AVD. Following frontline ABVD, 55.1% of patients received subsequent systemic therapy and 31.7% stem cell transplantation (SCT). At a median follow-up of 31.8 months, 82.0% of patients were alive (median rwOS, 101.2 months). Patients with stage III/IV cHL treated with frontline ABVD in the real world versus in clinical trials receive more subsequent therapy, including SCTs. Interim PET scans and Deauville scores were not universally obtained after treatment cycle 2, yet treatment de-escalation was observed. Patients with stage III/IV cHL may benefit from frontline A+AVD versus ABVD, as it improves OS and reduces the burden of subsequent therapy, including SCTs.

Retrospective Analysis With Propensity Score Matching of Peripheral T-Cell Lymphoma Treated Frontline With Brentuximab Vedotin and Chemotherapy.

BACKGROUND: Since Food and Drug Administration approval of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (A + CHP) as initial therapy for previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL), there has been limited research on real-world patient characteristics, treatment patterns, and clinical outcomes. METHODS: We retrospectively analyzed claims of patients with PTCL treated with frontline A + CHP or CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) using the Symphony Health Solutions database. Adults with International Classification of Diseases-9/10 PTCL diagnosis codes who initiated A + CHP or CHOP between November 2018 and July 2021 were included. A 1:1 propensity score matching analysis was performed that adjusted for potential confounders between groups. RESULTS: A total of 1344 patients were included (A + CHP, n = 749; CHOP, n = 595). Before matching, 61% were men; median age at index was 62 (A + CHP) and 69 (CHOP) years. The most common A + CHP-treated PTCL subtypes were systemic anaplastic large cell lymphoma (sALCL; 51%), PTCL-not otherwise specified (NOS; 30%), and angioimmunoblastic T-cell lymphoma (AITL; 12%); the most common CHOP-treated subtypes were PTCL-NOS (51%) and AITL (19%). After matching, similar proportions of patients treated with A + CHP and CHOP received granulocyte colony-stimulating factor (89% vs. 86%, P = .3). Fewer patients treated with A + CHP received subsequent therapy than CHOP overall (20% vs. 30%, P < .001) and specifically with the sALCL subtype (15% vs. 28%, P = .025). CONCLUSIONS: Characteristics and management of this real-world PTCL population who were older and had a higher comorbidity burden than that in the ECHELON-2 trial demonstrate the importance of retrospective studies when assessing the impact of new regimens on clinical practice.

Observations of Oncologists on Treatment Selection With Interim Positron Emission Tomography-Adapted Approaches in Classic Hodgkin Lymphoma: The Real-World CONNECT Study.

PURPOSE: We surveyed oncologists who treat classic Hodgkin lymphoma (cHL) as part of the CONNECT study to understand the treatment decision-making process, including the impact of positron emission tomography/computed tomography (PET/CT) imaging. METHODS: US physicians self-identifying as oncologists, hematologists, or hematologists/oncologists with ≥2 years of practice experience who treated ≥1 adult with stage III/IV cHL in the frontline setting in the last year were surveyed (October 19-November 16, 2020). Physician demographics, guideline adherence, and PET/CT utilization, interpretation, and access barriers were assessed. RESULTS: In total, 301 physicians participated in the survey. Eighty-eight percent of physicians gave somewhat-to-significant consideration to NCCN guidelines. Most physicians (94%; n = 284) reported obtaining a PET/CT scan at diagnosis; of these physicians, 97% reported obtaining an interim PET/CT scan for stage III/IV cHL, with 65% typically obtaining an interim PET/CT scan after cycle 2. The Deauville 5-point scale (5PS) was the primary scoring system used to review PET/CT results by 62% of physicians, with a positive score defined as ≥3 by 44%, ≥4 by 37%, and ≥2 by 12% of physicians. Fifty-five percent of physicians reported difficulty in obtaining PET/CT scans. CONCLUSION: Although most physicians considered NCCN guidelines when treating patients with stage III/IV cHL, interim PET/CT scans after cycle 2 were not universally obtained. When PET/CT scans were obtained, Deauville 5PS scores were not always provided, and variability existed on what defined a positive score. These findings suggest that opportunities exist for education and improved PET-adapted treatment approaches.

Estimating long-term progression-free and overall survival in patients with peripheral T-cell lymphoma: A US population-based oncology simulation model based on 5-year results from the ECHELON-2 trial.

BACKGROUND: The ECHELON-2 5-year update showed continued clinically meaningful improvements in progression-free survival (PFS) and overall survival with frontline (1L) A+CHP (brentuximab vedotin in combination with cyclophosphamide, doxorubicin, prednisone) vs CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in CD30-expressing peripheral T-cell lymphomas (PTCLs). OBJECTIVE: To estimate PTCL annual prevalence in the United States in 2031 without and with A+CHP using data from the ECHELON-2 5-year update. METHODS: Population-level outcomes were estimated using a dynamic oncology simulation model. Utilization of 1L CHOP (65% utilization) and CHOP plus etoposide (35% utilization) were varied over time and compared with scenarios incorporating 1L A+CHP (20%-50% utilization; base case: 40% utilization) per expert clinicians' opinion. Additional inputs included PTCL incidence and PFS for consolidation and post-1L therapies from published sources. PFS (51.4% [95% CI = 42.8%-59.4%] vs 43.0% [35.8%-50.0%]) and overall survival (hazard ratio = 0.72 [0.53-0.99]) for A+CHP and CHOP came from ECHELON-2. RESULTS: In 2031, an estimated 2,082 patients will be diagnosed with PTCL. Approximately 1,412 additional patients will be alive and progression free, and 106 fewer patients will require second-line therapy with 40% A+CHP utilization vs no A+CHP utilization. Varying 1L A+CHP utilization from 20%-50% vs no 1L A+CHP utilization added 732 to 1,752 patients alive and progression free. CONCLUSIONS: In this oncology simulation model, the improvements in survival outcomes seen with A+CHP vs CHOP in the ECHELON-2 5-year results translated into more estimated patients with PTCL progression free and alive for at least 5 years following 1L A+CHP vs CHOP and a decreased need for post-1L therapy. DISCLOSURES: This study was funded by Seagen Inc. Dr Liu and Dr Yu are employees and shareholders of Seagen Inc. Mr Bloudek is and Dr Mordi was an employee of Curta Health, which received funding from Seagen Inc. for the conduct of this study. Dr Burke received consulting fees from Genentech/Roche, AbbVie, Seattle Genetics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem, MorphoSys, Kura, Epizyme, BeiGene, Kymera, Novartis, Bristol Myers Squibb, TG Therapeutics, Lilly, and Nurix; and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events in speakers bureaus for BeiGene and Seagen Inc. Dr Phillips received consulting fees from AstraZeneca, MorphoSys, Epizyme, Roche/Genentech, Epizyme Eli Lilly, AbbVie, BeiGene, Pharmacyclics, Bristol Myers Squibb, Xencor, Seagen Inc., TG Therapeutics, Bayer, Incyte, and Gilead; and received payment for honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Epizyme and Seagen Inc.

Concerns About ABA-Based Intervention: An Evaluation and Recommendations.

For over 50 years, intervention methods informed by the principles of applied behavior analysis (ABA) have been empirically researched and clinically implemented for autistics/individuals diagnosed with autism spectrum disorder (ASD). Despite the plethora of evidence for the effectiveness of ABA-based interventions, some autism rights and neurodiversity activists have expressed concerns with ABA-based interventions. Concerns have included discontent with historical events and possible harm from the procedures and goals targeted. The purpose of this manuscript is to examine some expressed concerns about ABA-based intervention and suggest productive ways of moving forward to provide the best outcomes for autistics/individuals diagnosed with ASD. The authors represent stakeholders from multiple sectors including board certified behavior analysts, licensed psychologists, parents, and autistics/individuals diagnosed with ASD.

Targeted Genome Mining Reveals the Biosynthetic Gene Clusters of Natural Product CYP51 Inhibitors.

Lanosterol 14α-demethylase (CYP51) is an important target in the development of antifungal drugs. The fungal-derived restricticin 1 and related molecules are the only examples of natural products that inhibit CYP51. Here, using colocalizations of genes encoding self-resistant CYP51 as the query, we identified and validated the biosynthetic gene cluster (BGC) of 1. Additional genome mining of related BGCs with CYP51 led to production of the related lanomycin 2. The pathways for both 1 and 2 were identified from fungi not known to produce these compounds, highlighting the promise of the self-resistance enzyme (SRE) guided approach to bioactive natural product discovery.

Identifying the gaps in public dental services locations for people living with a disability in metropolitan Australia: a geographic information system (GIS)-based approach.

Objective The aim of this study was to identify the gaps in public dental service locations for people living with a disability in Australia, with in-depth analysis of Western Australia (WA). Methods Data from the Survey of Disability, Ageing and Carers and national census data were used to geographically model the prevalence of disability. Private and public dental practice data were integrated using QGIS, and a catchment area of 5km was used for public dental practices. This was then used to identify residential areas outside the 5-km catchment area. Further analysis was then done to determine how a potential service at these sites would improve geographic access for people with a disability residing within the area. Results In this study, 6162 private and 178 public dental practices were geo-coded, covering 39915 Statistical Area Level 1 regions and approximately 16 million people. Overall slightly more than half the people living with any disability resided within the 5-km catchment area of a public dental practice. WA (Perth) had the lowest coverage (48%), whereas New South Wales (Sydney) had the highest (71%). In WA (Perth), four sites were identified that would improve the overall coverage from 48% to 75%. Conclusion This study highlights the areas where there is low access to a dental service, particularly access to a public dental service, for people living with a disability. What is known about the topic? The distribution of people with a disability is associated with area-level measures of socioeconomic disadvantage. Access to dental care is a function of affordability, availability, accessibility, accommodation and acceptability. Previous studies identified problems in relation to access to dental care for people living with a disability, including wait times, costs and physical access to buildings. What does this paper add? This paper shows how geographical access to a dental service can be improved, by locating services in identified areas targeting people living with a disability. What are the implications for practitioners? The results of this study could be used to plan funding targeted at areas of need with a high burden of disease and low accessibility to services.

Recent developments in self-resistance gene directed natural product discovery.

Covering: 2000 to 2019Natural products (NPs) are important sources of human therapeutic agents and pesticides. To prevent self-harm from bioactive NPs, some microbial producers employ self-resistance genes to protect themselves. One effective strategy is to employ a self-resistance enzyme (SRE), which is a slightly mutated version of the original metabolic enzyme, and is resistant to the toxic NP but is still functional. The presence of a SRE in a gene cluster can serve as a predictive window to the biological activity of the NPs synthesized by the pathway. In this highlight, we summarize representative examples of NP biosynthetic pathways that utilize self-resistance genes for protection. Recent discoveries based on self-resistance gene identification have helped in bridging the gap between activity-guided and genome-driven approaches for NP discovery and functional assignment.

Prevalence of disability among the major cities in Australia 2012 with geographical representation of distribution in Western Australia.

ISSUE ADDRESSED: The aim of this study was to use a novel approach to geographically model the relationship between socio-economic disadvantage and prevalence of profound and severe disability. METHOD: This study used national census data and the survey of disability, ageing and carers data to geographically model the relationship between socio-economic disadvantage and prevalence of profound and severe disability. RESULT: The results in this study show that there were more people living in the least disadvantaged areas (wealthiest) when compared to the most disadvantaged (poorest) areas. Whereas for people with a disability as the relative socio-economic disadvantage of the area increased, the number of people reporting any disability also increased, with the highest number coming from the most disadvantaged areas. The maps show a significant distribution with fewer cases of disability in metropolitan areas and relatively higher number in the rural area along with the higher proportion of people with disability living in the relatively more disadvantaged areas. CONCLUSION: Socio-economic profile is one of the key factors influencing the various aspects of health and hence should hold an important place during policy making. Policy should be formulated and implemented to help reduce the inequality by either directly aiming at the most disadvantaged group or by trying to bridge the gap between them. SO WHAT?: This paper provides a geographic visualisation of the distribution of people with profound and severe disability to help identify priority areas with high prevalence of disability.