Pretreatment Intervals Research Articles

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination.

β-Nicotyrine (β-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. β-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine β-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm. The pharmacodynamics of β-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if β-Nic (0 - 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min β-Nic pretreatment delays. A second group of rats was trained to discriminate β-Nic and Nornicotine (Nornic) from saline to determine if β-Nic alone has interoceptive properties and whether they are similar to Nornic. β-Nic had similar binding affinity and efficacy at the α4β2 nicotinic receptor subtype as Nornic, ~50% of Nic efficacy. However, β-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that β-Nic dose-dependently increased the duration of nicotine's discriminative stimulus effects, especially at the 60-min delay. Drug naïve rats could reliably discriminate Nornic, but not β-Nic, from Sal. β-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.

English

Androgenesis is reported in a few tree crops such as citrus and papaya; however, there is little information available about guava. Different modified Chu (N6) media and cold pretreatments of floral buds were tested to induce embryogenic calli in the anthers of two white flesh guava cultivars, ‘Round’ and ‘Pyriform’. Four modified Chu (N6) media formulations, i.e., M1 (400 mgL-1 casein hydrolysate, 200 mgL-1 glutamine, 0.2 mgL-1NAA, 1.0 mgL-1 KIN, 0.5 mgL-1 6-BAP, 0.5 mgL-1 zeatin and 5% coconut water), M2 (400 mgL-1 casein hydrolysate, 200 mgL-1 glutamine, 0.2 mgL-1NAA, 1.0 mgL-1 KIN, 0.5 mgL-1 6-BAP), M10 (0.5 mgL-1 2,4-D), and M11 (0.5 mgL-1 2,4-D and 50 mgL-1 PVP) enhanced anther swelling and callus formation. Genotypic variability was found in pollen viability, phenolic exudation, and anther tissue browning after cold pretreatment for 0-72 hrs. intervals. Anthers of ‘Round’ showed more pollen viability across cold pretreatment intervals with less phenolic exudations and tissue browning than ‘Pyriform’. On both M10 and M11 media, anthers with uni-nucleate microspores developed embryogenic calli; however, anthers of ‘Pyriform’ resulted in more calli induction (69.58%) on M10 media, whereas anthers of ‘Round’ developed more calli (66.60%) on M11 media. The proliferating calli in white flesh ‘Round’ and ‘Pyriform’ cultivars and pink flesh ‘Round’ cultivar formed more embryogenic masses upon transfer to growth hormone-free Chu (N6) media under light conditions; however, embryos showed delayed maturity with limited germination. More genotypes shall be explored to enhance embryo germination, and embryogenic media shall be further fine-tuned. This study provides the foundation for the generation of homozygous lines in guava using androgenesis

Diagnostic and pre-treatment intervals among patients with cervical cancer attending care at the Uganda Cancer Institute: a cross-sectional study

BackgroundMajority of patients with cervical cancer in the low- and middle-income countries experience long diagnostic and pre-treatment intervals. This study sought to determine the factors associated with the diagnostic and pre-treatment intervals among patients with cervical cancer.MethodsThis was a cross-sectional study conducted at the Uganda Cancer Institute (UCI) during October 2019 to January 2020. Patients aged ≥ 18 years with histological diagnosis of cervical cancer were consecutively sampled. Data were collected using a pre-tested semi-structured questionnaire and a data abstraction form. Diagnostic intervals, defined as the time between first visit of a patient to a primary healthcare provider to time of getting confirmed diagnosis, of ≤ 3 months was defined as early & >3 months as late. Pre-treatment intervals, which is the time from histological diagnosis to starting cancer chemo-radiotherapy of ≤ 1 month was defined as early and > 1 month as late. Data were analysed using STATA version 14.0. We used modified Poisson regression models with robust variance to determine socio-demographic and clinical factors associated with the intervals.ResultsThe mean age of the participants was 50.0 ± 11.7 years. The median diagnostic and pre-treatment intervals were 3.1 (IQR: 1.4–8.2) months and 2.4 (IQR: 1.2–4.1) months respectively. Half of the participants, 49.6% (200/403) were diagnosed early; one in 5 patients, 20.1% (81/403) promptly (within one month) initiated cancer chemo-radiotherapy. Participants more likely to be diagnosed early included those referred from district hospitals (level 5) (aPR = 2.29; 95%CI: 1.60–3.26) and with squamous cell carcinomas (aPR = 1.55; 95%CI: 1.07–2.23). Participants more likely to be diagnosed late included those who first discussed their symptoms with relatives, (aPR = 0.77; 95%CI: (0.60–0.98), had > 2 pre-referral visits (aPR = 0.75; 95%CI (0.61–0.92), and had advanced stage (stages 3 or 4) (aPR = 0.68; 95%CI: 0.55–0.85). Participants more likely to initiate cancer chemo-radiotherapy early included older patients (≥ 60 years) (aPR = 2.44; 95%CI: 1.18–5.03). Patients likely to start treatment late were those who had ≥2 pre-referral visits (aPR = 0.63; 95%CI: 0.41–0.98) and those that took 3 - 6 months with symptoms before seeking healthcare (aPR = 0.52;95%CI: 0.29 - 0.95).ConclusionInterventions to promote prompt health-seeking and early diagnosis of cervical cancer need to target primary healthcare facilities and aim to enhance capacity of primary healthcare professionals to promptly initiate diagnostic investigations. Patients aged < 60 years require targeted interventions to promote prompt initiation of chemo-radiation therapy.

Factors associated with diagnostic and pre-treatment intervals among breast cancer patients attending care at the Uganda Cancer Institute: A cross-sectional study.

Most breast cancer (BC) patients in Uganda are diagnosed with advanced-stage disease and experience poor outcomes. This study examined the diagnostic and pre-treatment intervals and factors associated with these intervals among BC patients attending care at the Uganda Cancer Institute (UCI). This was a cross-sectional, facility-based study. Data were collected using structured questionnaire administered by trained research assistants and analyzed using STATA version 14.0. Modified Poisson regressions models were used to determine the strength of associations between independent variables and diagnostic and pre-treatment intervals. The mean age (±SD) of the 401 participants was 47.1 ± 11.7 years. Four in 10 participants had stage III (41.9%; n = 168) and over a third (34.7%; n = 140) stage IV cancers. The median interval from first consultation to diagnosis, i.e. diagnostic interval (DI) was 5.6 months (IQR: 1.5-17.0), while the median interval from histological diagnosis to start of chemotherapy, i.e. pre-treatment interval (PTI) was 1.7 months (IQR: 0.7-4.5). Majority (85%, n = 341) of participants were diagnosed at ≥3 months from first consultation with clinicians. Participants with tertiary education and those who lived within 100-199 km from the UCI were about four times and twice more likely to be diagnosed early (DI <3 months from first consultation) ([aPR = 3.88; 95% CI: 1.15-13.0] and [aPR = 2.19; 95% CI: 1.06-4.55]), respectively. About half (48.3%; n = 176) of participants started chemotherapy within 1 month of cancer diagnosis. Patients who lived more than 300 km from the UCI were less likely to start chemotherapy within 1 month of histology diagnosis of cancer. [Correction added on October 17, 2023 after first online publication. The term ', i.e.' has been included in the results section in this version.] CONCLUSION: Majority of breast cancer patients are diagnosed late and in advanced stages. There is need to promote all efforts toward timely diagnosis when cancers are still in early stages by identifying factors responsible for prolonged diagnostic intervals among breast cancer patients.

Barriers to timely identification of bipolar disorder in youth: a multidimensional perspective

Bipolar disorder (BD) in youth often goes unrecognized and therefore untreated. However, little is known about pathways to treatment of youth with BD and factors that influence the time taken for each stage of these pathways. In this article, we use the conceptual framework by Scott and colleagues called the Model of Pathways to Treatment as a foundation to explore the components of delay in the diagnosis and treatment of youth with BD. The total time from the onset of symptoms until treatment initiation was divided into four sequential intervals; i.e., the Appraisal, the Help-seeking, the Diagnostic and the Pre-treatment intervals and potential disease, patient, and healthcare system/provider factors that influence each interval were identified. This multidimensional conceptual framework can offer a systematic approach to understanding and exploring barriers to early identification and interventions in BD, which is a crucial step in the development of strategies to facilitate prompt diagnosis and treatment. We hope this work contributes to the discussion on delayed diagnosis and treatment of youth with BD and provides a roadmap to inform future research studies and policy decisions.

Correlation between duration of edentulism and severity of obstructive sleep apnea in elderly edentulous patients.

ObjectivesTo investigate the correlation between duration of edentulism and severity of obstructive sleep apnea in elderly edentulous patients.Material and Methods1,017 patients aged 55-65 years, with a history of edentulism of 12-60 months were screened. Detailed history of tooth loss and period of edentulism was recorded for the 414 patients who tested positive for OSA (obstructive sleep apnea). Complete dentures were prepared for each patient and they were trained to use the dentures as a mandibular advancement device (MAD) during sleep at night. Apnea-hypopnea index (AHI) data at pre-treatment, six months and one-year post-treatment time intervals was recorded. A correlation between the period of untreated edentulism and severity of OSA and improvement post-treatment was derived in this study.ResultsMean duration of edentulism was 12.14±2.57 months and mean AHI was 16.62±13.24. For every three month increase in the duration of edentulism (after initial 6 months of total tooth loss), there was a statistically significant increase in severity of OSA. Patients who are edentulous for more than 15 months are increasingly vulnerable to OSA.DiscussionSeverity of OSA in afflicted long-term edentulous patients was in direct relation to the period of untreated edentulism and regressed likewise with concomitant denture wear and mandibular advancement during sleep at night. Early prosthetic rehabilitation of edentulous patients is imperative to obviate morbidity of OSA.

Influence of the adhesive bonding protocol on the inflammatory cellular response and gelatinolytic activity in human teeth

The aim of this paper was to assess the biocompatibility and expression of metalloproteinase -9 of two dentin bonding agents in human teeth, using different methods of dentin pre-treatment and different time intervals. Deep Class I cavities were prepared on the occlusal surface of 18 sound molars. Restorations were performed with XP Bond™ (Dentsply) and Futurabond® DC (VOCO). After 30, 90 or 120 days, the teeth were extracted and processed for histological and immunohistochemical assessment. In XP Bond group, was observed a moderate inflammatory infiltrate and immunoreactivity of metalloproteinase -9 in all storage intervals. In Futurabond DC group, a slight inflammatory infiltrate was found in the first intervals. After 120 days, the inflammatory infiltrate was either slight or absent, while the tissue morphology remained normal. The immunoreactivity of metalloproteinase -9 was considered moderate, except for two specimen after 120 days, that demonstrated no immunoreactivity. Therefore, etch-and-rinse adhesives exhibited a more intense pulpal response than self-etching agents. When performing adhesive restorations in medium and deep cavities in human teeth, the use of a self-etching adhesive strategy should be considered in view of the lower induction of inflammatory and proteolytic activity. Further studies of molecular events should be conducted, taking into consideration the possible inflammatory pulp reactions that can contribute to the success of restorative procedures.

Disparities and interventions in the timeliness of endometrial cancer diagnosis and treatment in the United States: a scoping review protocol

BackgroundDisparities in the stage at diagnosis of endometrial cancer (EC) account for a significant proportion of the disparities in morbidity and mortality experienced by vulnerable groups in the USA. Evidence suggests that disparities in timeliness of care and treatment play a significant role in stage at diagnosis. Despite an increase in literature on EC disparities, the issue remains largely unchanged. The objectives of this review will be to synthesize the evidence to identify important remaining research questions and inform future interventions to reduce the disparity in stage at diagnosis of EC in the USA.MethodsThis scoping review protocol will use the five-step framework developed by Arksey and O’Malley. A literature search will be conducted from January 2000 onwards in PubMed, EMBASE, Scopus, and Cochrane CENTRAL databases. Studies on delays in care of EC will be included if they were published in English and reported findings for the US population. Two reviewers will independently screen all citations, full-text articles, and abstract data. The study methodological quality and bias will be appraised using appropriate tools. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods. The literature search, data extraction, and evidence synthesis will be informed by the Pathway to Treatment Model, which divides time to cancer care initiation into appraisal, help-seeking, diagnostic, and pre-treatment intervals. Results will be reported in accordance with the PRISMA statement.DiscussionEC disparities research is currently benefitting form a growing expectation that studies have a real impact on disparities. Patient, healthcare, and disease factors impact the amount of time patients spend in different intervals of the Pathway to Treatment Model, so research and interventions aimed at reducing disparities in EC survival should be designed with cognizance to how these factors impact their target population. Reviews on disparities in stage at diagnosis of EC exist but do not provide a comprehensive picture of the pathway to treatment. This review will seek to provide an expanded bedrock of evidence for future studies to build on as they aim to more actively reduce EC disparities.Trial registrationOpen Science Framework (osf.io/v2zxy).

Time-to-Treatment in Oral Cancer: Causes and Implications for Survival.

Simple SummaryStage of the disease at diagnosis has been recognized as one of the most important prognostic markers for oral cancer. Unfortunately, still two thirds of patients are diagnosed at an advanced stage of disease with a 5-year survival rate of 50% or less. Although the detection of oral cancer at an early stage is the most effective means to improve survival and reduce morbidity, in the past years, there has been little change in the diagnosis of oral cancer at early stages, which is believed to be a result of delays in diagnosis and treatment of oral cancer, among other independent factors. Following the Aarhus statement, developed in effort to standardize the design, methods and reporting of studies concerning time-intervals in early diagnosis research, the review assessed the causes that influence the patient, diagnosis and pre-treatment intervals in the pathway of time-to-treatment in oral cancer and its impact on survival.The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

RADT-18. LONG-TERM FOLLOW-UP OF PATIENTS TREATED WITH GAMMA KNIFE® STEREOTACTIC RADIOSURGERY (GK-SRS) FOR VESTIBULAR SCHWANNOMA (VS)

Abstract PURPOSE GK-SRS is an accepted definitive treatment option for appropriately selected patients with VS. To assess long-term outcomes in VS patients treated with GK-SRS, we retrospectively evaluated all patients treated at our institution from 2007-2019. METHODS For VS patients treated with GK-SRS from 2007-2019, clinical data (symptoms, physical exams, audiograms, and imaging) was collected via retrospective chart review at pre-treatment and standard follow-up intervals (6 weeks, 6 months, 12 months, then annually). Descriptive analyses, including the proportions of patients in different grades of clinical parameters, are reported. For each clinical parameter, only patients with both pre- and post-treatment data were included in the evaluation set used for analysis. RESULTS Of 177 patients identified, 46 were excluded from the evaluable set (age &amp;lt; 18 years, prior resection, NF-2, or no follow-up). Among the remaining 131, median follow-up was 42 months (6 weeks to 11 years), and 36.6% completed 5+ years of follow-up. At time of treatment, median age was 61 years, and median Karnofsky Performance Score was 90. 58.0% of lesions were left-sided, and 42.0% were right-sided. The majority were Koos grade II (37.4%) or III (38.2%); the remainder were grade I (13.0%) or IV (11.5%). Pre-treatment central necrosis and ventriculomegaly were present in 39.7% and 4.6%, respectively. Following treatment, audiogram analysis with Gardner-Robertson Hearing Score demonstrated no change in 48.9%, some level of decline in 47.8%, and improvement in 3.3% at last follow-up. 97.7% had House-Brackmann scores of I at diagnosis; the remainder were House-Brackmann II. House-Brackmann scores remained unchanged at last follow-up for 96.9%, improved for 1.6%, and worsened for 1.6%. Salvage therapy in the form of surgery (n=5) or repeat GK-SRS (n=2) was necessary in 5.3% (n=6 for progression; n=1 for trigeminal symptoms). CONCLUSION Long-term follow-up demonstrates that GK-SRS remains a well-tolerated, primary definitive treatment for VS.

Effect of condylar osteochondroma resection through an intraoral approach on the masticatory functions: a preliminary evaluation based on occlusion and temporomandibular joint functions

With this research, we aimed to evaluate the effect of condylar osteochondroma (OC) resection through an intraoral approach on the masticatory functions. Resection of condylar OC was carried out via an intraoral approach with the help of three-dimensional (3D) design, endoscope, and navigation system. The T-Scan III computerised occlusal analysis system was used to evaluate the occlusal force distribution, recorded at pre-treatment (T1) and post-treatment (T2) intervals. Records of the clinical examination of the temporomandibular joint (TMJ), including maximal interincisal opening, mandibular lateral and forward movements, were also collected. Ten patients with condylar OC were enrolled in this study. The difference of force distribution between bilateral occlusion was reduced in T2 compared with T1 (11.92% ± 4.41% vs 48.52 % ± 28.37%, p<0.05), indicating better occlusal force distribution obtained after surgery. There was no significant difference in functions of the TMJ, such as maximal interincisal opening, and mandibular lateral and forward movements between T2 and T1 (p>0.05). Accordingly, condylar OC resection through an intraoral approach would obtain a satisfactory occlusal balance with no impairment of the temporomandibular joint functions.

Efficacy of Group Conversation Intervention in Individuals with Severe Profiles of Aphasia.

An estimated 390,000 to 520,000 individuals with severe aphasia (IWSA) currently live in the United States. IWSA experience profound social isolation, which is associated with a wide range of negative health outcomes, including mortality. Treatments for severe aphasia frequently focus on compensatory communication approaches or a discrete communication act rather than on participation-based treatment. The purpose of this study was to determine whether IWSA demonstrated improved performance on standardized language measures, patient-reported outcome measures, and connected speech samples as a result of client-centered conversation group treatment. Results of assessments conducted at pretreatment, posttreatment, and maintenance intervals were variable across participants. All participants demonstrated improvement in at least one of the outcome measures considered. Importantly, none of these measures fully captured how IWSA were able to convey their thoughts in supported conversation. The results lend support for the use of conversation treatment for, and for further study in, this subpopulation of individuals with aphasia.

Characterization of the antinociceptive effects of intrathecal DALDA peptides following bolus intrathecal delivery.

Background and aims We systematically characterized the potency and side effect profile of a series of small opioid peptides with high affinity for the mu opioid receptor. Methods Male Sprague Dawley rats were prepared with intrathecal (IT) catheters, assessed with hind paw thermal escape and evaluated for side effects including Straub tail, truncal rigidity, and pinnae and corneal reflexes. In these studies, DMT-DALDA (dDAL) (H-Dmt-D-Arg-Phe-Lys-NH2 MW=981), dDALc (H-Dmt-Cit-Phe-Lys-NH2 MW=868), dDALcn (H-Dmt-D-Cit-Phe-Nle-NH2 MW=739), TAPP (H-Tyr-D-Ala-Phe-Phe-NH2 MW=659), dDAL-TICP ([Dmt1]DALDA-(CH2)2-NH-TICP[psi]; MW=1519), and dDAL-TIPP (H-Dmt-D-Arg-Phe-Lys(Nε-TIPP)-NH2 were examined. In separate studies, the effects of approximately equiactive doses of IT DMT DALDA (10 pmol), morphine (30 nmol) and fentanyl (1 nmol) were examined on formalin-induced flinching at different pretreatment intervals (15 min - 24 h). Results (1) All agents resulted in a dose-dependent reversible effect upon motor function (Straub Tail>Truncal rigidity). (2) The ordering of analgesic activity (%MPE) at the highest dose lacking reliable motor signs after bolus delivery was: DMT-DALDA (80%±6/3 pmol); dDALc (75%±8/1 pmol); dDALcn (84%±10/300 pmol); TAPP (56%±12/10 nmol); dDAL-TICP (52%±27/300 pmol). (3) All analgesic effects were reversed by systemic (IP) naloxone (1 mg/kg). Naltrindole (3 mg/kg, IP) had no significant effect upon the maximum usable peptide dose. (4) Tolerance and cross-tolerance development after 5 daily boluses of DMT-DALDA (3 pmol) and morphine (30 nmol) revealed that both agents displayed a progressive decline over 5 days. (5) Cross-tolerance assessed at day 5 revealed a reduction in response to morphine in DMT-DALDA treated animal but not DMT-DALDA in the morphine treated animal, indicating an asymmetric cross-tolerance. (6) IT DMT-DALDA, morphine and fentanyl resulted in significant reductions in phase 1 and phase 2 flinching. With a 15 min pretreatment all drugs resulted in comparable reductions in flinching. However, at 6 h, the reduction in flinching after DMT-DALDA and morphine were comparably reduced while fentanyl was not different from vehicle. All effects on flinching were lost by 24 h. Conclusions These results emphasize the potent mu agonist properties of the DALDA peptidic structure series, their persistence similar to morphine and their propensity to produce tolerance. The asymmetric cross-tolerance between equiactive doses may reflect the relative intrinsic activity of morphine and DMT-DALDA. Implications These results suggest that the DALDA peptides with their potency and duration of action after intrathecal delivery suggest their potential utility for their further development as a spinal therapeutic to manage pain.

From symptom discovery to treatment - women's pathways to breast cancer care: a cross-sectional study

BackgroundTypically, women in South Africa (SA) are diagnosed with breast cancer when they self-present with symptoms to health facilities. The aim of this study was to determine the pathway that women follow to breast cancer care and factors associated with this journey.MethodsA cross-sectional study was conducted at a tertiary hospital in the Western Cape Province, SA, between May 2015 and May 2016. Newly diagnosed breast cancer patients were interviewed to determine their socio-demographic profile; knowledge of risk factors, signs and symptoms; appraisal of breast changes; clinical profile and; key time events in the journey to care. The Model of Pathways to Treatment Framework underpinned the analysis. The total time (TT) between a woman noticing the first breast change and the date of scheduled treatment was divided into 3 intervals: the patient interval (PI); the diagnostic interval (DI) and the pre-treatment interval (PTI). For the PI, DI and PTI a bivariate comparison of median time intervals by various characteristics was conducted using Wilcoxon rank-sum and Kruskal-Wallis tests. Cox Proportional-Hazards models were used to identify factors independently associated with the PI, DI and PTI.ResultsThe median age of the 201 participants was 54 years, and 22% presented with late stage disease. The median TT was 110 days, with median patient, diagnostic and pre-treatment intervals of 23, 28 and 37 days respectively. Factors associated with the PI were: older age (Hazard ratio (HR) 0.59, 95% CI 0.40–0.86), initial symptom denial (HR 0.43, 95% CI 0.19–0.97) and waiting for a lump to increase in size before seeking care (HR 0.51, 95% CI 0.33–0.77). Women with co-morbidities had a significantly longer DI (HR 0.67, 95% CI 0.47–0.96) as did women who mentioned denial of initial breast symptoms (HR 4.61, 95% CI 1.80–11.78). The PTI was associated with late stage disease at presentation (HR 1.78, 95% CI 1.15–2.76).ConclusionThe Model of Pathways to Treatment provides a useful framework to explore patient’s journeys to care and identified opportunities for targeted interventions.

Language Changes Following Combined Aphasia and Apraxia of Speech Treatment.

Combined Aphasia and Apraxia of Speech Treatment (CAAST) is a newly developed treatment shown to increase production of accurate content in narrative discourse for persons with aphasia and apraxia of speech. The purpose of this post hoc study was to further describe lexical and morphosyntactic changes associated with changes in content production. Existing probe data from 8 persons with aphasia who had completed CAAST were used to complete analyses of morphosyntactic production, lexical diversity, and novelty of content. Language analyses were completed using discourse samples obtained at numerous pretreatment and posttreatment intervals. All participants demonstrated gains in morphosyntactic language output for treated items, which extended to untreated sets for 7 participants. All 8 increased in production of novel content. Lexical diversity increases were evident for most participants. Although there were some similarities in language changes, there was substantial variability across response profiles. CAAST, previously associated with positive treatment effects for production of accurate content, also appears to facilitate acquisition and generalization of morphosyntactic complexity, lexical diversity, and novelty of content for individuals with nonfluent aphasia. Further investigation is needed to determine causality and appropriate clinical application. https://doi.org/10.23641/asha.5912530.

Abstract IA33: Pathways to breast cancer care in South Africa

Abstract Breast cancer is a major public health burden and remains the commonest cancer among women worldwide. In 2012, 1.7 million women were newly diagnosed with breast cancer and 522 000 women died of the disease with the majority of cases (53%) and deaths (63%) occurring in low- and middle-income countries. In South Africa (SA) breast cancer is the most commonly diagnosed cancer among women and accounts for 16% of all female cancer deaths. Similar to other developing countries, the majority of patients in SA present with late stage disease, which is associated with a poorer prognosis. SA does not have a national mammography-screening program. Typically women with breast symptoms self-present to primary health care facilities and are referred to secondary or tertiary level health facilities if further diagnostic work-up is required to diagnose breast cancer. Appropriate recognition of breast symptoms, improved access to health facilities and accurate investigation of symptomatic women are essential to down stage breast cancer. Worldwide, the majority of cancers (85-90%) are diagnosed on the basis of symptomatic presentation despite cancer screening programs. Studies have shown that for symptomatic breast cancer, shorter time to presentation to a health care provider is associated with early stage disease, and better breast cancer survival. Further, a substantial proportion of late stage diagnosis of poorly differentiated breast cancer cases could be avoided if patients had presented within one month of detecting symptoms. Consequently, understanding breast cancer symptom awareness, and responses to symptoms by both patients and providers are important in developing interventions to promote timely breast cancer diagnosis. For people with potential symptoms of cancer, the pathway to cancer diagnosis is complex. Internationally, research has shown that personal, disease and healthcare factors are associated with the timeliness of seeking care for symptomatic disease and can contribute to late stage presentation. Primary care providers also play a pivotal role in timely cancer diagnosis and referral. Understanding the influence of these factors on the pathway women follow to breast cancer diagnosis is vital to the development of interventions. The Model of Pathways to Treatment provides a useful research framework to explore and understand patient's journeys to care as it takes into account the complex and dynamic nature of help-seeking behavior. The Model identifies five key events in the pathway to care viz. detection of bodily changes; perceived reasons to discuss symptoms with a health care provider; first consultation with a health care provider; diagnosis and start of treatment, and four important intervals between these events: the appraisal, help seeking, diagnostic and the pre-treatment intervals. Using the Model, this presentation will outline what is currently known about patient pathways to breast cancer care in SA and what further research is required to develop targeted interventions to promote timely diagnosis of breast cancer. Citation Format: Jennifer Moodley. Pathways to breast cancer care in South Africa [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA33.

Pathways to Lung Cancer Diagnosis: A Qualitative Study of Patients and General Practitioners about Diagnostic and Pretreatment Intervals.

Pathways to lung cancer diagnosis and treatment are complex. International evidence shows significant variations in pathways. Qualitative research investigating pathways to lung cancer diagnosis rarely considers both patient and general practitioner views simultaneously. To describe the lung cancer diagnostic pathway, focusing on the perspective of patients and general practitioners about diagnostic and pretreatment intervals. This qualitative study of patients with lung cancer and general practitioners in Australia used qualitative interviews or a focus group in which participants responded to a semistructured questionnaire designed to explore experiences of the diagnostic pathway. The Model of Pathways to Treatment (the Model) was used as a framework for analysis, with data organized into (1) events, (2) processes, and (3) contributing factors for variations in diagnostic and pretreatment intervals. Thirty participants (19 patients with lung cancer and 11 general practitioners) took part. Nine themes were identified during analysis. For the diagnostic interval, these were: (1) taking patient concerns seriously, (2) a sense of urgency, (3) advocacy that is doctor-driven or self-motivated, and (4) referral: "knowing who to refer to." For the pretreatment interval, themes were: (5) uncertainty, (6) psychosocial support for the patient and family before treatment, and (7) communication among the multidisciplinary team and general practitioners. Two cross-cutting themes were: (8) coordination of care and "handing over" the patient, and (9) general practitioner knowledge about lung cancer. Events were perceived as complex, with diagnosis often being revealed over time, rather than as a single event. Contributing factors at patient, system, and disease levels are described for both intervals. Patients and general practitioners expressed similar themes across the diagnostic and pretreatment intervals. Significant improvements could be made to health systems to facilitate better patient and general practitioner experiences of the diagnostic pathway. This novel presentation of patient and general practitioner perspectives indicates that systemic interventions have a role in timely and appropriate referrals to specialist care and coordination of investigations. Systemic interventions may alleviate concerns about urgency of diagnostic workup, communication, and coordination of care as patients transition from primary to specialist care.

Pathways to anxiety-depression comorbidity: A longitudinal examination of childhood anxiety disorders.

Anxiety disorders are prevalent in youth and associated with later depressive disorders. A recent model posits three distinct anxiety-depression pathways. Pathway 1 represents youth with a diathesis to anxiety that increases risk for depressive disorders; Pathway 2 describes youth with a shared anxiety-depression diathesis; and Pathway 3 consists of youth with a diathesis for depression who develop anxiety as a consequence of depression impairment. This is the first partial test of this model following cognitive-behavioral treatment (CBT) for child anxiety. The present study included individuals (N = 66; M age = 27.23 years, SD = 3.54) treated with CBT for childhood anxiety disorders 7-19 years (M = 16.24; SD = 3.56) earlier. Information regarding anxiety (i.e., social phobia (SoP), separation anxiety disorder (SAD), generalized anxiety disorder (GAD)) and mood disorders (i.e., major depressive disorder (MDD) and dysthymic disorders) was obtained at pretreatment, posttreatment, and one or more follow-up intervals via interviews and self-reports. Evidence of pathways from SoP, SAD, and GAD to later depressive disorders was not observed. Treatment responders evidenced reduced GAD and SoP over time, although SoP was observed to have a more chronic and enduring pattern. Evidence for typically observed pathways from childhood anxiety disorders was not observed. Future research should prospectively examine if CBT treatment response disrupts commonly observed pathways.

Timeliness in Breast Cancer Treatment-The Sooner, the Better.

Defining the impact of delays in breast cancer care is a difficult task. Although the question—“when should I undergo treatment?”—is simple, necessary, and asked by patients every day, our understanding of its therapeutic implications is incomplete. Prospective trials comparing longer vs shorter pretreatment intervals would not be ethically acceptable to patients or clinicians, and will not be performed. Therefore, we rely on retrospective and observational data. Numerous factors confound analysis of the correlation between treatment delay and survival outcomes, and many of these (including level of comorbidity, treatment compliance, social support, and access to health care) are impossible to capture fully even with highly granular data sets and sophisticated statistical models. However, despite the inherent pitfalls of retrospective analyses, the articles by Bleicher et al 1 and ChavezMacGregor et al 2 in this issue of JAMA Oncology are an important step toward defining the risks of delay.

Serum Antibodies to HPV16 Early Proteins Warrant Investigation as Potential Biomarkers for Risk Stratification and Recurrence of HPV-Associated Oropharyngeal Cancer

Human papillomavirus (HPV) is responsible for increasing incidence of oropharyngeal cancer. At present, there are no biomarkers in the surveillance algorithm for HPV-positive oropharyngeal cancer (HPV-OPC). HPV16 E6 antibody precedes oropharyngeal cancer diagnosis. If HPV16 E6 indeed precedes primary diagnosis, it is similarly expected to precede disease recurrence and may have a potential role as a biomarker for surveillance of HPV-OPC. To determine whether HPV antibody titers have a potential role as early markers of disease recurrence or prognosis, a retrospective pilot study was designed to determine whether HPV16 early antibody titers E6, E7, E1, and E2 decrease after treatment of HPV16-positive OPC. Trends in pretreatment, early (≤6 months after treatment), and late posttreatment (>6 months after treatment) HPV16 antibody titers were examined. There were 43, 34, and 52 subjects with serum samples available for pretreatment, early, and late posttreatment intervals. Mean pretreatment antibody levels were higher than posttreatment antibody levels. Average antibody levels decreased significantly over time for E6 (Ptrend = 0.001) and E7 (Ptrend < 0.001). Six disease recurrences were observed during the follow-up period (median, 4.4 years). In univariate analysis, a log-unit increase in pretreatment E6 titer was significantly associated with increased risk of disease recurrence (HR, 5.42; 95% CI, 1.1-25.7; P = 0.03). Therefore, levels of antibodies to HPV16 early oncoproteins decline after therapy. Higher E6 titers at diagnosis are associated with significant increases in the risk of recurrence. These data support the prospective evaluation of HPV16 antibodies as markers of surveillance and for risk stratification at diagnosis.