Prevalence and risk characteristics of COVID-19 in outpatients: A cross-sectional study of New York-area clinics.

Outpatients can be at heightened risk of COVID-19 due to interaction between existing non-communicable diseases in outpatients and infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study measured the magnitude of COVID-19 prevalence and explored related risk characteristics among adult outpatients visiting medicine clinics within a New York state-based tertiary hospital system. Data were compiled from 63,476 adult patients visiting outpatient medicine clinics within a New York-area hospital system between March 1, 2020, and August 28, 2020. The outcome was a clinical diagnosis of COVID-19. Crude and adjusted prevalence ratios (PR) of a COVID-19 were analyzed using univariable and multivariable Poisson regression with robust standard errors. The prevalence of COVID-19 was higher among these outpatients (3.0%) than in the total population in New York State (2.2%) as of August 28, 2020. Multivariable analysis revealed adjusted prevalence ratios significantly greater than one for male sex (PR=1.10), age 40 to 64 compared to <40 (PR=1.19), and racial/ethnic minorities in comparison to White patients (Hispanic: PR=2.76; Black: PR=1.89; and Asian/others: PR=1.56). Nonetheless, factors including the advanced age of ≥65 compared to <40 (PR=0.69) and current smoking compared to non-smoking (PR=0.60) were related to significantly lower prevalence. Therefore, the prevalence of COVID-19 in outpatients was higher than that of the general population. The findings also enabled hypothesis generation that routine clinical measures comprising sex, age, race/ethnicity, and smoking were candidate risk characteristics of COVID-19 in outpatients to be further verified by designs capable of assessing temporal association.

Patient-reported outcomes with neoadjuvant vs adjuvant systemic therapy for operable breast cancer.

BACKGROUND: Neoadjuvant systemic therapy (NAST) is used for large operable or highly proliferative breast cancers. It is not known whether psychological outcomes differ according to the treatment sequence (chemotherapy or surgery first) or tumour response. METHODS: This was a planned analysis of a multi-institutional single arm longitudinal study of patients considering NAST for operable breast cancer. Participants completed patient reported outcome questionnaires before and after the decision about NAST, between chemotherapy and surgery, and 12 months after diagnosis. RESULTS: Fifty-nine women enrolled. Fourteen of 51 (28%) who received NAST experienced pathological complete response (pCR). Patients who had surgery first (n = 7) had higher baseline anxiety, and a greater decrease in anxiety at 12 months follow up, compared with patients who received NAST (n = 50) (a decrease from baseline of 34 pts vs 17 points; p = 0.033). Distress declined at a similar rate in surgery first and NAST groups. Mean satisfaction with decision score post-decision was significantly lower in the adjuvant group compared with NAST (22 vs 26, p = 0.02). No differences were seen between patients with pCR vs residual cancer in: distress, anxiety, satisfaction with decision, fear of progression, and decision regret. CONCLUSION: Most patients in this study proceeded with NAST when their surgeon offered it as an option. This exploratory analysis suggests that patients who chose surgery first tended to be more anxious, and had lower satisfaction with their decision, than those who had NAST. In patients who had NAST, lack of pCR does not appear to correlate with adverse psychological outcomes.

Identification of key determinants in Porphyromonas gingivalis host-cell invasion assays.

The periodontal pathogen Porphyromonas gingivalis can invade host cells, a virulence trait which may contribute to the persistence of infection at subgingival sites. Whilst the antibiotic protection assay has been commonly employed to investigate and quantify P. gingivalis invasion, data obtained have varied widely and a thorough investigation of the factors influencing this is lacking. We investigated the role of a number of bacterial and host-cell factors and report that the growth phase of P. gingivalis, source (laboratory strain vs. clinical strain), host-cell identity (cell line vs. primary), host-cell lysis method, and host-cell passage number had no significant effect on bacterial invasion. However, incubation time, host-cell seeding density, method of quantification (viable count vs. DNA), and whether host cells were plated or in suspension, were shown to influence invasion. Also, cells isolated by rapid adhesion to fibronectin exhibited higher levels of P. gingivalis invasion, possibly as a result of increased levels of active α5ß1 integrin. Interestingly, this may represent a population of cells with stem cell-like properties. This study provides important new information by identifying the most important factors that influence P. gingivalis invasion assays and may help to explain variations in the levels previously reported.

Dances With Denial: Have Medical Oncology Outpatients Conveyed Their End-of-Life Wishes and Do They Want To?

Objectives: This study surveyed a sample of medical oncology outpatients to determine (1) the proportion who have already discussed and documented their end-of-life (EOL) wishes; (2) when and with whom they would prefer to convey their EOL wishes; (3) the EOL issues they would want to discuss; and (4) the association between perceived cancer status and advance care planning (ACP) participation. Methods: Adult medical oncology outpatients were approached in the waiting room of an Australian tertiary treatment center. Consenting participants completed a pen-and-paper survey assessing participation in ACP, preferences for conveying EOL wishes, timing of EOL discussions, and EOL issues they want to be asked about. Results: A total of 203 patients returned the survey (47% of eligible). EOL discussions occurred more frequently with support persons (47%) than with doctors (7%). Only 14% had recorded their wishes, and 45% had appointed an enduring guardian. Those who perceived their cancer as incurable were more likely to have participated in ACP. If facing EOL, patients indicated that they would want family involved in discussions (85%), to be able to write down EOL wishes (82%), and to appoint enduring guardians (91%). Many (45%) preferred the first discussion to happen when their disease became incurable. Slightly less than one-third thought discussions regarding EOL should be patient-initiated. Most agreed doctors should ask about preferred decision-making involvement (92%), how important it is that pain is managed well (95%), and how important it is to remain conscious (82%). Fewer (55%) wanted to be asked about the importance of care extending life. Conclusions: Many patients would like to have discussions regarding EOL care with their doctor and involve their support persons in this process. Only a small percentage of respondents had discussed EOL care with their doctors, recorded their wishes, or appointed an enduring guardian. The first step requires clinicians to ask whether an individual patient wishes to discuss EOL issues, in what format, and at what level of detail.

Single-Arm Longitudinal Study to Evaluate a Decision Aid for Women Offered Neoadjuvant Systemic Therapy for Operable Breast Cancer.

Background: Neoadjuvant systemic therapy (NAST) is an increasingly used treatment option for women with large operable or highly proliferative breast cancer. With equivalent survival outcomes between NAST and up-front surgery, the situation-specific preference-sensitive nature of the decision makes it suitable for a decision aid (DA). This study aimed to develop and evaluate a DA for this population. Methods: A DA booklet was developed according to international standards, including information about adjuvant and neoadjuvant treatment, outcome probabilities, and a values clarification exercise. Eligible women, considered by investigators as candidates for NAST, were enrolled in a multi-institutional, single-arm, longitudinal study. Patient-reported outcome measure questionnaires were completed pre- and post-DA, between chemotherapy and surgery, and at 12 months. Outcomes were feasibility (percentage of eligible patients accessing the DA); acceptability to patients (percentage who would recommend it to others) and clinicians (percentage who would use the DA in routine practice); and decision-related outcomes. Results: From 77 eligible women, 59 were enrolled, of whom 47 (79.7%; 95% CI, 69.4-89.9) reported having read the DA; 51 completed the first post-DA questionnaire. Of these 51, 41 participants (80.4%; 95% CI, 69.5-91.3) found the DA useful for their decision about NAST. Of 18 responding investigators, 16 (88.9%; 95% CI, 74.4-103.4) indicated they would continue to use the DA in routine practice. Post-DA, decisional conflict decreased significantly (P<.01); anxiety and distress decreased significantly; and 86.3% (95% CI, 73.7-94.3) achieved at least as much decisional control as they desired. Conclusions: This DA was feasible and acceptable to patients and clinicians, and improvement in decision-related outcomes was demonstrated when used in combination with clinical consultations. This DA could safely be implemented into routine practice for women considering NAST for operable breast cancer.

The Right Place at the Right Time: Medical Oncology Outpatients' Perceptions of Location of End-of-Life Care.

Background: Helping people achieve their preferred location of care is an important indicator of quality end-of-life (EOL) care. Using a sample of Australian medical oncology outpatients, this study examined (1) their preferred location of EOL care; (2) their perceived benefits and worries of receiving care in that location; (3) the percentage who had discussed preferences with their doctor and/or support person; and (4) whether they wanted their doctor to ask them where they wanted to die. Methods: Adults with a confirmed diagnosis of cancer were approached between September 2015 and January 2016 in the waiting room of an Australian oncology outpatient clinic. Consenting participants completed a home-based pen-and-paper survey indicating preferred location of care, perceived benefits and worries of that location, whether they had discussed preferences with their doctors, and whether they were willing to be asked about their preferences. Results: A total of 203 patients returned the survey (47% of those eligible). Less than half preferred to be cared for at home (47%), 34% preferred a hospice/palliative care unit, and 19% preferred the hospital. Common benefits and worries associated with locations included perceived burden on others, familiarity of environment, availability of expert medical care, symptom management, and likelihood of having wishes respected. More patients had discussed preferences with their support persons (41%) than doctors (7%). Most wanted a doctor to ask them about preferred location of care (87%) and thought it was important to die in the location of their choice (93%). Conclusions: Patients were willing to have clinicians to ask them where they wanted to die, although few had discussed their preferences with doctors. Although home was the most preferred location for many patients, the overall variation suggests that clinicians should adopt a systematic approach to eliciting patient preferences.

Wound tension and 'closability' with keystone flaps, V-Y flaps and primary closure: a study in fresh-frozen cadavers.

BACKGROUND: Previous publications have implied that the keystone flap provides mechanical benefits compared to primary closure. This has not been objectively demonstrated. METHODS: Elliptical defects were created in 'fresh-frozen' cadaveric specimens. Two approaches were used to investigate the potential mechanical benefits of keystone flaps. Experiment 1 (wound closure): 18 defects were incrementally enlarged until they could not be closed primarily either with a single 'midpoint' suture or with a continuous suture. Attempts were then made to close these wounds with island flaps: 13 keystone flaps (seven 'type IIA' and six 'Sydney Melanoma Unit (SMU) modification') and five V-Y flaps. Experiment 2 (tension reduction): 28 defects were fashioned to be 'closable' under high tension. The 'pre-flap tension' was measured with a single midpoint suture and tensiometer. Fourteen keystone flaps (seven type IIA and seven SMU modifications) and seven V-Y flaps were then developed and mobilized with no flap constructed on the remaining seven 'primary closure' wounds. The secondary defects resulting from flap mobilization were closed leaving the primary defect unsutured. The primary defect 'post-flap tension' was then measured using the same technique. RESULTS: For Experiment 1, V-Y flaps enabled closure in four of five 'unclosable' defects. Keystone flaps did not enable closure in any of the 13 cases (P < 0.001). For Experiment 2, the V-Y flap (n = 7) was the only group that produced a significant drop in wound tension across the primary defect (mean 'pre-flap' to 'post-flap' tension change: -53%, 95% CI: -67 to -39%, P < 0.001). CONCLUSION: The data raise questions about the biomechanical benefits of keystone flaps.

Progress towards the total synthesis of hamigerans C and D: a direct approach to an elaborated 6-7-5 carbocyclic core.

The hamigeran family of natural products has been the target of numerous synthetic efforts because of its biological activity and interesting structural properties. Herein, we disclose our efforts toward the synthesis of hamigerans C and D, unique among the initially isolated members because of their 6-7-5 carbocyclic core. Our approach directly targets this tricyclic motif by sequential Negishi and Heck coupling reactions, yielding an advanced intermediate with all necessary carbons and sufficient functionality poised for completion of the synthesis of these two natural products.

Do medical oncology patients and their support persons agree about end-of-life issues?

BACKGROUND: The perceptions of those called on to make decisions on behalf of patients who lack capacity at the end of life must accurately reflect patient preferences. AIMS: To establish the extent to which the views of medical oncology outpatients are understood by their support persons, specifically with regards to (i) preferred type and location of end-of-life care, (ii) preferred level of involvement in end-of-life decision-making and (iii) whether the patient has completed an advance care plan or appointed an enduring guardian. METHODS: Adults with a confirmed cancer diagnosis and their nominated support persons were approached between September 2015 and January 2016 in the waiting room of an Australian tertiary referral clinic. Consenting participants completed a pen-and-paper survey. Nominated support persons answered the same questions from the patient's perspective. RESULTS: In total, 208 participants (39% of eligible dyads) participated. Observed agreement across the five outcomes ranged from 54% to 84%. Kappa values for concordance between patient-support person responses were fair to moderate (0.24-0.47) for enduring guardian, decision-making, advance care plan and care location outcomes. A slight level of concordance (k = 0.15; 95% confidence interval: -0.02, 0.32) was found for the type of care outcome. CONCLUSION: Relying on support persons' views does not guarantee that patients' actual preferences will be followed. Strategies that make patient preferences known to healthcare providers and support persons while they still have the capacity to do so is a critical next step in improving quality cancer care.

Addiction medicine ethics: relapse, no lapse and the struggle to treat addicts like everyone else.

Two case studies are presented as a focus for discussion of ethics in addiction medicine. The first is that of the alcohol-dependent patient who receives a liver transplant. The second is that of a heroin-dependent patient who continues to inject himself while in a general medical ward. I make some comments about the obligations of doctors to treat those who cause harm to themselves as they would treat those who are 'not responsible'.

Investigation of a Novel Predictive Biomarker Profile for the Outcome of Periodontal Treatment.

BACKGROUND: An ability to predict the response to conventional non-surgical treatment of a periodontal site would be advantageous. However, biomarkers or tests devised to achieve this have lacked sensitivity. The aim of this study is to assess the ability of a novel combination of biomarkers to predict treatment outcome of patients with chronic periodontitis. METHODS: Gingival crevicular fluid (GCF) and subgingival plaque were collected from 77 patients at three representative sites, one healthy (probing depth [PD] ≤3 mm) and two diseased (PD ≥6 mm), at baseline and at 3 and 6 months after treatment. Patients received standard non-surgical periodontal treatment at each time point as appropriate. The outcome measure was improvement in probing depth of ≥2 mm. Concentrations of active enzymes (matrix metalloproteinase [MMP]-8, elastase, and sialidase) in GCF and subgingival plaque levels of Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum were analyzed for prediction of the outcome measure. RESULTS: Using threshold values of MMP-8 (94 ng/µL), elastase (33 ng/µL), sialidase (23 ng/µL), and levels of P. gingivalis (0.23%) and T. forsythia (0.35%), receiver operating characteristic curves analysis demonstrated that these biomarkers at baseline could differentiate healthy from diseased sites (sensitivity and specificity ≥77%). Furthermore, logistic regression showed that this combination of these biomarkers at baseline provided accurate predictions of treatment outcome (≥92%). CONCLUSION: The "fingerprint" of GCF enzymes and bacteria described here offers a way to predict the outcome of non-surgical periodontal treatment on a site-specific basis.

A Decision Aid for Women Considering Neoadjuvant Systemic Therapy for Operable Invasive Breast Cancer: Development and Protocol of a Phase II Evaluation Study (ANZ1301 DOMINO).

BACKGROUND: Neoadjuvant systemic therapy is offered to selected women with large and/or highly proliferative operable breast cancers. This option adds further complexity to an already complex breast cancer treatment decision tree. Patient decision aids are an established method of increasing patient involvement and knowledge while decreasing decisional conflict. There is currently no decision aid available for women considering neoadjuvant systemic therapy. OBJECTIVE: We aimed to develop a decision aid for women diagnosed with operable breast cancer and considered suitable for neoadjuvant systemic therapy, and the protocol for a multicenter pre-post study evaluating the acceptability and feasibility of the decision aid. METHODS: The decision aid was developed through literature review, expert advisory panel, adherence to the International Patient Decision Aid Standards, and iterative review. The protocol for evaluation of the decision aid consists of the following: eligible women will undertake a series of questionnaires prior to and after using the decision aid. The primary endpoint is decision aid acceptability to patients and investigators and the feasibility of use. Secondary endpoints include change in decisional conflict, participant knowledge, and information involvement preference. Feasibility is defined as the proportion of eligible participants who use the decision aid to help inform their treatment decision. RESULTS: This study has recruited 29 out of a planned 50 participants at four Australian sites. A 12-month recruitment period is expected with a further 12-months follow-up. CONCLUSIONS: The decision aid has the potential to allow patients with operable breast cancer, who have been offered neoadjuvant systemic therapy, decreased decisional conflict, and greater involvement in the decision. If this study finds that an online decision aid is feasible and acceptable, it will be made widely available for routine clinical practice. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12614001267640; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12614001267640&isBasic=True (Archived by WebCite at http://www.webcitation.org/6gh7BPZdG).

A pilot study of active enzyme levels in gingival crevicular fluid of patients with chronic periodontal disease.

AIM: To determine whether combinations of enzymes in gingival crevicular fluid (GCF) can act as improved biomarkers compared with single enzymes for predicting the outcome of treatment and also for diagnosing the clinical status of sites. METHODS: Thirty subjects with chronic periodontitis were recruited to a 12-month longitudinal pilot study. GCF samples from three representative sites: healthy (≤3 mm), deep non-bleeding (NB) (≥6 mm) and deep bleeding (DB) (≥6 mm) sites and clinical data were collected at baseline, 3 months, 6 months and 12 months following periodontal treatment. Active enzyme levels (MMP-8, cathepsin G, elastase, trypsin-like activity and sialidase) in GCF samples were assessed. The enzyme profiles and clinical data of each site were analysed for correlation and logistic regression was performed to find the predictive value of the active enzyme levels regarding the outcome of treatment. RESULTS: Twenty-two individuals completed the study. All active enzyme levels were significantly higher in diseased sites than healthy sites. Logistic regression showed that the combination of MMP8, elastase and sialidase provided accurate predictions of treatment outcome (88% for NB and 86% for DB), which was significantly better than each enzyme alone (61%). CONCLUSION: This pilot has suggested that combined active enzyme profiling could provide significant prediction of outcome of treatment.

Towards an Operational Definition of Clinical Competency in Pharmacy.

OBJECTIVE: To estimate the inter-rater reliability and accuracy of ratings of competence in student pharmacist/patient clinical interactions as depicted in videotaped simulations and to compare expert panelist and typical preceptor ratings of those interactions. METHODS: This study used a multifactorial experimental design to estimate inter-rater reliability and accuracy of preceptors' assessment of student performance in clinical simulations. The study protocol used nine 5-10 minute video vignettes portraying different levels of competency in student performance in simulated clinical interactions. Intra-Class Correlation (ICC) was used to calculate inter-rater reliability and Fisher exact test was used to compare differences in distribution of scores between expert and nonexpert assessments. RESULTS: Preceptors (n=42) across 5 states assessed the simulated performances. Intra-Class Correlation estimates were higher for 3 nonrandomized video simulations compared to the 6 randomized simulations. Preceptors more readily identified high and low student performances compared to satisfactory performances. In nearly two-thirds of the rating opportunities, a higher proportion of expert panelists than preceptors rated the student performance correctly (18 of 27 scenarios). CONCLUSION: Valid and reliable assessments are critically important because they affect student grades and formative student feedback. Study results indicate the need for pharmacy preceptor training in performance assessment. The process demonstrated in this study can be used to establish minimum preceptor benchmarks for future national training programs.

Double meanings will not save the principle of double effect.

In an article somewhat ironically entitled "Disambiguating Clinical Intentions," Lynn Jansen promotes an idea that should be bewildering to anyone familiar with the literature on the intention/foresight distinction. According to Jansen, "intention" has two commonsense meanings, one of which is equivalent to "foresight." Consequently, questions about intention are "infected" with ambiguity-people cannot tell what they mean and do not know how to answer them. This hypothesis is unsupported by evidence, but Jansen states it as if it were accepted fact. In this reply, we make explicit the multiple misrepresentations she has employed to make her hypothesis seem plausible. We also point out the ways in which it defies common sense. In particular, Jansen applies her thesis only to recent empirical research on the intentions of doctors, totally ignoring the widespread confusion that her assertion would imply in everyday life, in law, and indeed in religious and philosophical writings concerning the intention/foresight distinction and the Principle of Double Effect.

Evaluation of a rural nurse-led clinic for female sexual dysfunction.

OBJECTIVE: The objective of this study was to explore changes in the sexual function of women who attended a rural nurse-led female sexual dysfunction clinic. DESIGN: This exploratory study was designed as a one-group pre-test/post-test design from a convenience sample of women attending the clinic. SETTING: The setting was a women's health centre located in regional Western Australia. PARTICIPANTS: One hundred eleven women aged between 18 and 65 years were recruited from clinic attendees. MAIN OUTCOME MEASURE(S): The Australian version of the validated McCoy Female Sexuality Questionnaire was completed before the first appointment (T0), and 1 (T1) and 6 months (T2) after the last appointment. RESULTS: Women attending the clinic reported significant increases in sexual desire, satisfaction and orgasm quality and achievement at 1 and 6 months after their last appointment. There was also a significant increase in satisfaction with their main sexual partner at 6 months. CONCLUSIONS: This study confirmed the value of an innovative approach to managing female sexual dysfunction in a rural area with workforce shortages and limited health services. It is recommended that care by a nurse-led multidisciplinary team be used in the management of sexual dysfunction. Further research is needed to see if this model of care would be effective in other settings.