Development and validation of a novel questionnaire to describe and assess sensations and triggers associated with refractory and unexplained chronic cough.

INTRODUCTION: Refractory or unexplained chronic cough (RUCC) is a common clinical problem with no effective diagnostic tools. The Sensations and Triggers Provoking Cough questionnaire (TOPIC) was developed to characterise cough in RUCC versus cough in other conditions. METHODS: Content analysis of participant interviews discussing the sensations and triggers of chronic cough informed TOPIC development. Participants with chronic cough completed the draft-TOPIC (a subset repeating 5-7 days later), St George's Respiratory Questionnaire (SGRQ), Cough Severity Diary (CSD) and Global Rating of Change Scale. The draft-TOPIC item list was reduced in hierarchical and Rasch analysis to refine the questionnaire to the TOPIC. RESULTS: 49 items describing the triggers and sensations of cough were generated from participant interviews (RUCC n=14, chronic obstructive pulmonary disease (COPD) n=11, interstitial lung disease (ILD) n=10, asthma n=11, bronchiectasis n=3, cystic fibrosis n=7). 140 participants (median age 60.0 (19.0-88.0), female 56.4%; RUCC n=39, ILD n=38, asthma n=45, COPD n=6, bronchiectasis n=12) completed draft-TOPIC, where items with poor 'fit' for RUCC were removed to create TOPIC (8 trigger items, 7 sensation items). Median TOPIC score was significantly higher in RUCC (37.0) vs ILD (24.5, p=0.009) and asthma (7.0, p<0.001), but not bronchiectasis (20.0, p=0.318) or COPD (18.5, p=0.238), likely due to small sample sizes. The Rasch model demonstrated excellent fit in RUCC (χ2=22.04, p=0.85; PSI=0.88); as expected. When all participant groups were included, fit was no longer demonstrated (χ2=66.43, p=0.0001, PSI=0.89) due to the increased heterogeneity (CI=0.077). TOPIC correlated positively with SGRQ (r=0.47, p<0.001) and CSD (r=0.63, p<0.001). The test-retest reliability of TOPIC (intraclass correlation coefficient) was excellent (r=0.90, p<0.001). CONCLUSIONS: High TOPIC scores in the RUCC patients suggest their cough is characterised by specific sensations and triggers. Validation of TOPIC in cough clinics may demonstrate value as an aid to identify features of RUCC versus cough in other conditions.

Adoption of vaginally assisted natural orifice transluminal endoscopic surgery for hysterectomy: A single tertiary experience.

BACKGROUND: Vaginal hysterectomy (VH) rate is declining despite being considered as the optimal minimally invasive option for hysterectomy with reduced operative time and length of stay compared with laparoscopic hysterectomy (LH). Vaginal assisted natural orifice transluminal endoscopic surgery hysterectomy (VANH) combines the advantages of both vaginal and endoscopic approach to surgery. AIMS: To report feasibility and early experience of a single surgeon adopting VANH at a tertiary Australian hospital. MATERIALS AND METHODS: Prospective review of the first 20 VANH cases with complete data set collected retrospectively including patient demographics, indication for surgery and perioperative outcomes. RESULTS: The median age of the first 20 participants was 51.5 years (47-57 years of age) and the median body mass index was 33.5 kg/m2 (27.8-38.3 kg/m2). The predominant indication was complex hyperplasia with atypia (12/20, 60%). The median parity was two (1-3) where four patients were nulliparous. The median blood loss was 125 mL (100-200 mL) with an operative time of 149 min (138-198 min) and median weight of the specimen of 181.5 g (66.5-219 g). The mean length of stay was 1.4 days (1-2 days). Five cases had conversion to laparoscopy and the majority (80%) occurred within the first ten cases. CONCLUSIONS: VANH is feasible but there is a learning curve to achieve competence in this technique, which requires adequate training in the early stages of adoption with careful case selection. Until further robust data is available to determine the clinical benefit and safety profile of VANH, patients should be carefully counselled and the decision on mode of hysterectomy be individualised.

Productive cough, a forgotten phenotype of refractory chronic cough.

BACKGROUND: Refractory chronic cough (RCC) patients typically complain of a dry cough. Sputum production in these patients has rarely been described in the literature. However, sputum production in RCC may be common, troublesome and particularly challenging to manage. AIMS: We aimed to characterise patients referred to our regional specialist cough clinic who have significant sputum production (≥1 teaspoon of sputum daily) and compare their demographics, symptomatology and investigation results to those presenting with a dry RCC. METHODS: A retrospective case note analysis of all consecutive referrals to a tertiary cough clinic identified as having a productive cough (≥1 teaspoon of sputum daily) was performed over a 12-month period. They were compared to a paired number of patients with dry RCC. RESULTS: Patients with productive cough represented nearly a quarter (98/398, 24.6 %) of new patient referrals to the clinic. Demographic information, symptomatology and investigation results were comparable to those with a dry RCC. Over a third, 35.8 % of patients with a productive cough reported expectorating an egg-cupful of sputum or more a day. Nearly half, 40% of those with high volume sputum production (≥egg-cupful daily) had both a normal CT thorax and normal spirometry. CONCLUSIONS: Patients with RCC can expectorate significant volumes of sputum in the absence of underlying lung disease. This group have similar demographics to those with dry RCC. This is the first piece of work to our knowledge to describe this cohort. Future work needs to acknowledge this forgotten phenotype to ensure that they receive comprehensive evaluation and evidenced based treatment.

Eating disorders and COVID-19 - different or just more?

BACKGROUND: COVID-19 saw an increase in child mental health presentations internationally. Clinicians analogised the exponential increase in anorexia nervosa to a 'tsunami' or 'outbreak', raising parallel concerns regarding medical and psychological risks (Marsh in The Guardian, 2021; Leask in NZ Herald, 2021; Monteleone et al. in Eat Weight Disord 26(8):2443-2452, 2021) . It is unclear whether Ireland emulated this picture of increased referrals with increased medical compromise. AIMS: This paper examines both rates and clinical profiles of child eating disorder presentations in the Republic of Ireland (ROI), across different clinical settings. METHODS: Following ethical approval, retrospective chart reviews were conducted in a community eating disorder service and in two paediatric hospital settings. The time frame of the different studies ranged from January 2016 to December 2022. RESULTS: Community eating disorder services saw significantly higher referral rates post COVID-19 (3.78/month vs. 2.31/month, p = 0.02), with a shorter duration of illness (4.8 months vs. 7.4 months, p = 0.001), but no significant difference in ideal body weight % (IBW%) at referral (85.32% vs. 83.7%, p = 0.1). Both paediatric hospitals witnessed significantly increased referrals post-COVID-19 (hospital 1; 4.38/month vs. 1.93/month, p = 0.0001; hospital 2; 2.8/month vs. 0.92/month, p < 0.0001), but no significant difference in IBW% at assessment (hospital 1; 82.7% vs. 81.39%, p = 0.673; hospital 2; 81.5% vs. 83%, p = 0.563). There was no significant difference in clinical profile, management, or duration of hospital stay. CONCLUSIONS: This study supports the growing consensus of a pandemic specific increase in eating disorder referrals to both medical and psychiatry services. However, there was little to indicate a change in clinical profile or severity. Ongoing monitoring of referrals is necessary to ensure adequate service availability and expertise.

The Future of Basic Science: Development of the Next Generation of Mechanistic Researchers in Female Pelvic Medicine.

INTRODUCTION AND HYPOTHESIS: The International Urogynecological Association (IUGA) brought together senior and junior members actively engaged in scholarly and educational activities for a consensus conference centered on developing a strategy for sustainable training of the next generation of mechanistic researchers in female pelvic medicine. METHODS: Four a priori identified major foci were explored in a half-day virtual consensus conference. Participants included representatives from various countries and disciplines with diverse backgrounds-clinicians, physician-scientists, and basic scientists in the fields of urogynecology, biomechanical engineering, and molecular biology. Following a keynote address, each focus area was first tackled by a dedicated breakout group, led by the Chair(s) of the most relevant IUGA committees. The break-out sessions were followed by an iterative discussion among all attendees to identify mitigating strategies to address the shortage of mechanistic researchers in the field of female pelvic medicine. RESULTS: The major focus areas included: research priorities for IUGA basic science scholar program; viable strategies for sustainable basic science mentorship; core competencies in basic science training; and the challenges of conducting complex mechanistic experiments in low-resource countries. Key gaps in knowledge and core competencies that should be incorporated into fellowship/graduate training were identified, and existing training modalities were discussed. Recommendations were made for pragmatic approaches to increasing the exposure of trainees to learning tools to enable sustainable training of the next generation of basic science researchers in female pelvic medicine worldwide. CONCLUSIONS: The attendees presented multiple perspectives to gain consensus regarding critical areas of need for training future generations of mechanistic researchers. Recommendations for a sustainable Basic Science Scholar Program were developed using IUGA as a platform. The overarching goal of such a program is to ensure a successful bench-to-bedside-and-back circuit in Urogynecology and Pelvic Reconstructive Surgery, ultimately improving lives of millions of women worldwide through scientifically rational effective preventative and therapeutic interventions.

Rare case of strangulated primary acquired perineal hernia causing small bowel obstruction requiring emergency operative repair.

Primary acquired perineal hernia is rare with only 100 reported cases in the literature. Emergency presentations of intestinal obstruction secondary to perineal hernia are very rare and to-date, there are only eight cases reported in the literature. We present a case of a 74-year-old lady who presented with a small bowel obstruction secondary to strangulated perineal hernia in the absence of pelvic exenteration or abdominoperineal resection requiring operative repair via combined open transabdominal and transperineal approach. To our knowledge, this case represents the first reported case of intestinal obstruction secondary to primary acquired perineal hernia in the absence of pelvic exenteration or abdominoperineal resection.

Safety of curative-intent lung cancer surgery in older patients (octogenarians): A contemporary multicentre cohort study.

INTRODUCTION: Despite octogenarians representing an ever-increasing proportion of patients with lung cancer, there is a paucity of evidence describing outcomes after lung resection for these patients. We aimed to evaluate short and mid-term outcomes for octogenarians after lung resection. MATERIALS AND METHODS: A total of 5,470 consecutive patients undergoing lung resection for primary lung cancer from 2012-2019 in two UK centres were included. Primary outcomes were perioperative, 90-day, and one-year mortality in the octogenarian vs. non-octogenarian cohort. Appropriate statistical tests were used to compare outcomes between octogenarian and non-octogenarian patients. Secondary outcomes were post-operative complications and to validate the performance of the Thoracoscore model in the octogenarian cohort. RESULTS: Overall, 9.4% (n=513) of patients were aged ≥80. The rates of 90-day mortality, one-year mortality, and post-operative atrial fibrillation were significantly higher for octogenarians. The one-year mortality rate for octogenarians fell significantly over time (2012-2015: 16.5% vs 2016-2019: 10.2%, p=0.034). Subgroup analysis (2016-2019 only) demonstrated no significant difference in peri-operative, 90-day, or one-year mortality between octogenarian and non-octogenarian patients. Validation of the Thoracoscore model demonstrated modest discrimination and acceptable calibration. DISCUSSION: Mortality for octogenarians fell significantly over time in this study. Indeed, when confined to the most recent time period, comparable rates of both 90-day and one-year mortality for octogenarian and non-octogenarian patients were seen. Whilst preventative strategies to reduce the incidence of post-operative atrial fibrillation in octogenarians should be considered, these findings demonstrate that following appropriate patient selection, octogenarians can safely undergo lung resection for lung cancer.

Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance.

OBJECTIVES: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI). DESIGN: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size. SETTING: 4 UK pleural disease centres (February 2019-January 2020). PARTICIPANTS: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up. OUTCOME MEASURES: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression. RESULTS: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)). CONCLUSIONS: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500. TRIAL REGISTRATION NUMBER: ISRCTN12840870.

Bronchoscopy for refractory/unexplained cough with mucus.

INTRODUCTION: Refractory/unexplained cough (RUCC) is typically associated with throat symptoms and a dry cough. Some patients attending specialist cough clinics however, report sputum production (>1 tablespoon daily) and atypical sensations (urge-to-cough in chest). Bronchoscopy findings in this specific cohort have rarely been described. AIMS: We aimed to evaluate bronchoscopy, bronchoalveolar lavage (BAL) cell differential and microbiology findings in RUCC with mucus production. METHODS: We retrospectively reviewed case notes, procedure results and treatment of patients undergoing bronchoscopy for RUCC with more than a tablespoon of sputum daily. RESULTS: Data were included from 54 patients with RUCC, normal or trivial findings on CT (Computerised Tomography) imaging and no response to guideline-directed treatment of their cough. Most (84%) patients had BAL neutrophilia and excessive dynamic airway collapse (EDAC) was seen in 31%. Treatment strategies in these patients differed to those adopted in typical RUCC associated with a dry cough. Management was influenced or changed in 48/54 (89%) of the patients undergoing bronchoscopy. CONCLUSIONS: Bronchoscopy provides high diagnostic value in RUCC with mucus production (>1 tbsp daily), identifying specific treatable traits including neutrophilic airway inflammation and EDAC.

Chronic cough and inflammatory bowel disease: an under-recognised association?

Respiratory complications of inflammatory bowel disease (IBD) are common and may be under-recognised. Chronic cough may present many years after a colectomy for IBD, is typically productive and can be very responsive to inhaled corticosteroids. https://bit.ly/3DrHNoy.

Brain imaging in lung cancer staging: A real-world, multi-centre study of prevalence of brain metastases, impact on treatment and re-modelling of the NICE health economic analysis.

INTRODUCTION: In 2019, the National Institute for Health and Care Excellence (NICE) updated their recommendations with respect to brain imaging in the staging of non-small cell lung cancer (NSCLC) based on an analytic cost-effectiveness model using published data and modelling assumptions from committee experts. In this study, we aimed to re-run this model using real-world multi-centre UK data. MATERIALS AND METHODS: Retrospective data was collected on consecutive patients with radically treatable clinical stage II and III lung cancer from eleven acute NHS Trusts during the calendar year 01/01/2018 to 31/12/2018. Following a written application to the NICE lung cancer guideline committee, we were granted access to the NG122 brain imaging economic model for the purpose of updating the input parameters in line with the real-world findings from this study. RESULTS: A total of 444 patients had data for analysis. The combined prevalence of occult brain metastases was 6.2% (10/165) in stage II and 6% (17/283) in stage III, compared to 9.5% and 9.3% used in the NICE economic model. 30% of patients with clinical stage III NSCLC and occult BMs on pre-treatment imaging went onto complete the planned curative intent treatment of extracranial disease, 60% completed SRS to the brain and 30% completed WBRT. This compares to 0%, 10% and 0% in the NICE assumptions. The health economic analysis concluded that brain imaging was no longer cost-effective in stage II disease (ICERs £50,023-£115,785) whilst brain imaging remained cost-effective for stage III patients (ICERs 17,000-£22,173), with MRI being the most cost-effective strategy. CONCLUSION: This re-running of the NICE health economic model with real-world data strongly supports the NICE guideline recommendation for brain imaging prior to curative-intent treatment in stage III lung cancer but questions the cost-effectiveness of CT brain imaging prior to curative-intent treatment in stage II lung cancer.

Doctors in distress: The personality profile of derailing doctors.

OBJECTIVE: This study looked at the bright and dark-side personality profile of distressed and potentially derailing doctors (82% male). The derailing doctors were on average 48.75 years old, and from many specialities, in particular, general practice and surgery. METHOD: In all, a group of 77 derailing British doctors, and a control group of 357 doctors completed a valid multi-dimensional test of bright-side (normal) personality (NEO-PI-R) and one of dysfunctional interpersonal themes (sub-clinical personality disorders) (HDS: Hogan Development Survey). RESULTS: Controlling for sex and age, the derailing doctors were more Neurotic (less resilient), and less Agreeable, Conscientious, Extraverted and Open-to- Experience. They were also more Excitable (Borderline), Sceptical (Paranoid), Cautious (Avoidant), Reserved (Schizoid), Leisurely (Passive Aggressive) and Bold (Narcissistic). Discriminant analysis showed age, Neuroticism, Extraversion, Leisurely and Excitable were, in that order, the greatest personality discriminators between those who did and did not derail. CONCLUSION: More research needs to be done on doctor derailment to inform the selection and training of doctors.

Systematic review of the effectiveness of non-pharmacological interventions used to treat adults with inducible laryngeal obstruction.

INTRODUCTION: Inducible laryngeal obstruction (ILO) describes transient laryngeal closure during respiration and can cause significant morbidity. Non-pharmacological behavioural therapy is the commonly cited treatment but efficacy is largely unknown. AIM: To synthesise the current evidence base on the effectiveness of non-pharmacological interventions used to treat adults with ILO. METHODS: Electronic databases (Medline/Embase/CINAHL/PsycINFO/AMED/CENTRAL) were systematically searched, informed by a population, intervention, comparison, outcome framework. Two reviewers independently screened a representative sample, with lead-author completion due to excellent inter-rater reliability. Data was extracted using a predefined piloted form. Methodological quality was appraised (blindly by two reviewers) using the Joanna Briggs Institute Critical Appraisal Tools. A narrative synthesis was performed due to heterogeneity of studies (PROSPERO registration number: CRD42020213187). RESULTS: Initial searching identified 3359 records. Full-text screening occurred in 92 records and 14 studies, comprising 527 participants, were deemed eligible. All studies were low-level evidence (observational by design, with four case reports), with a high risk of bias; none contained control arms for comparison. Intervention description was inconsistently and poorly described but direction of effect was positive in 76% of outcomes measured. The majority of studies showed a reduction in symptom scores and improved direct laryngeal imaging post intervention; there was an overall reduction, 59.5%, in healthcare utilisation. DISCUSSION: The literature is in an embryonic state and lacks robust data to truly inform on the effectiveness of non-pharmacological interventions used to treat adults with ILO. However, positive signals in the synthesis performed support non-pharmacological treatment approaches and further development is warranted.

The diagnostic pathway in lung cancer patients with best supportive care decisions: are there lessons to be learnt?

INTRODUCTION: A proportion of patients with lung cancer will not be suitable for anti-cancer treatment and are managed with best supportive care (BSC). The aim of this retrospective case series analysis was to critically review the use of diagnostic and staging investigations in patients who were ultimately managed with BSC. METHODS: A retrospective review of all lung cancer patients with a multidisciplinary team outcome of BSC from 01 June 2018 to 01 June 2019 was performed. Patients were categorised into those with an early BSC decision and those that underwent further investigations prior to a BSC decision (investigations beyond initial computed tomography (CT)). Patient demographics, clinical characteristics and outcomes were collated and analysed. RESULTS: Seventy-seven lung cancer patients managed with BSC were identified. Patients were elderly (average age 79 years), functionally limited (80% World Health Organization performance status ≥3), frail (70% clinical frailty score ≥6) and had advanced stage disease (90% stage III/IV). Thirty-one (40%) underwent further investigations beyond the initial CT prior to the BSC decision. The most common types of further investigations were endobronchial ultrasound-guided transbronchial needle aspiration (27/31; 74%), positron emission tomography - CT (18/31; 45%) and CT-guided lung biopsy (7/31; 23%). This is despite high levels of consultant chest physician review at first assessment (71%), cancer nurse specialist involvement (97%), specialist palliative care involvement (65%), a high pathological confirmation rate of sampling procedures (89%) and adequacy of molecular testing. The most common reason for a BSC recommendation was a lack of fitness for systemic therapy (17/31; 55%). Six out of thirty-one (19%) patients deteriorated rapidly and died on the cancer pathway and 5/31 (16%) patients had inadequate renal function for systemic anti-cancer treatment. There was low utilisation of serum epidermal growth factor receptor mutation testing across the study cohort (2/77; 3%). DISCUSSION: In an older, functionally limited and frail patient with lung cancer, there is a risk of over-investigation. Impaired renal function is an important clinical factor to identify early to support discussions in this cohort. There will always be an unavoidable proportion of patients that undergo further investigations (often in search of rare targetable mutations) and are then ultimately recommended for best supportive care; such cases could form the basis of specific review and learning for lung cancer services.

Management of non-cystic fibrosis bronchiectasis.

Bronchiectasis is a common respiratory condition, characterised by abnormal bronchial dilatation, that often leads to recurrent airway infection and inflammation. It is an increasingly recognised respiratory condition, both as a primary lung disease but also co-existing with other respiratory diseases, such as chronic obstructive pulmonary disease and asthma. Diagnosis can have important treatment implications. There are shared systematic approaches to treatment, such as sputum clearance techniques, prompt treatment of exacerbations and, in certain circumstances, regular antibiotic therapy. It is vital to target antibiotic therapy appropriately, and knowledge of the patient's airway microbiology can assist with this. Certain infective and colonising organisms, such as Pseudomonas aeruginosa, cause worse patient outcomes and so need prompt treatment with appropriate antibiotics. In addition to this general management approach, there are many different underlying causes of bronchiectasis that should be identified wherever possible, to support more targeted therapy and prevent disease progression. This article provides a guide to the key principles of diagnosing and managing bronchiectasis, and outlines situations where more specialist respiratory support is required.

Is there clinical value in performing capsaicin cough challenges in patients with severe asthma?

Heightened capsaicin cough sensitivity is independently associated with poor asthma control in moderate-to-severe asthma patients https://bit.ly/3mkbLkI.

Triplet Therapy with Palbociclib, Taselisib, and Fulvestrant in PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers.

Cyclin-dependent kinase 4/6 (CDK4/6) and PI3K inhibitors synergize in PIK3CA-mutant ER-positive HER2-negative breast cancer models. We conducted a phase Ib trial investigating the safety and efficacy of doublet CDK4/6 inhibitor palbociclib plus selective PI3K inhibitor taselisib in advanced solid tumors, and triplet palbociclib plus taselisib plus fulvestrant in 25 patients with PIK3CA-mutant, ER-positive HER2-negative advanced breast cancer. The triplet therapy response rate in PIK3CA-mutant, ER-positive HER2-negative cancer was 37.5% [95% confidence interval (CI), 18.8-59.4]. Durable disease control was observed in PIK3CA-mutant ER-negative breast cancer and other solid tumors with doublet therapy. Both combinations were well tolerated at pharmacodynamically active doses. In the triplet group, high baseline cyclin E1 expression associated with shorter progression-free survival (PFS; HR = 4.2; 95% CI, 1.3-13.1; P = 0.02). Early circulating tumor DNA (ctDNA) dynamics demonstrated high on-treatment ctDNA association with shorter PFS (HR = 5.2; 95% CI, 1.4-19.4; P = 0.04). Longitudinal plasma ctDNA sequencing provided genomic evolution evidence during triplet therapy. SIGNIFICANCE: The triplet of palbociclib, taselisib, and fulvestrant has promising efficacy in patients with heavily pretreated PIK3CA-mutant ER-positive HER2-negative advanced breast cancer. A subset of patients with PIK3CA-mutant triple-negative breast cancer derived clinical benefit from palbociclib and taselisib doublet, suggesting a potential nonchemotherapy targeted approach for this population.This article is highlighted in the In This Issue feature, p. 1.

Syncope: a complication of chronic cough.

Cough syncope is a rare but serious and potentially life-threatening complication of chronic cough. Early identification, comprehensive diagnostic evaluation and appropriate driving advice are fundamental to protect patients and the public. https://bit.ly/3CDAqYa.

Improving the quality of person-centred healthcare from the patient perspective: development of person-centred quality indicators.

IMPORTANCE: International efforts are being made towards a person-centred care (PCC) model, but there are currently no standardised mechanisms to measure and monitor PCC at a healthcare system level. The use of metrics to measure PCC can help to drive the changes needed to improve the quality of healthcare that is person centred. OBJECTIVE: To develop and validate person-centred care quality indicators (PC-QIs) measuring PCC at a healthcare system level through a synthesis of the evidence and a person-centred consensus approach to ensure the PC-QIs reflect what matters most to people in their care. METHODS: Existing indicators were first identified through a scoping review of the literature and an international environmental scan. Focus group discussions with diverse patients and caregivers and interviews with clinicians and experts in quality improvement allowed us to identify gaps in current measurement of PCC and inform the development of new PC-QIs. A set of identified and newly developed PC-QIs were subsequently refined by Delphi consensus process using a modified RAND/UCLA Appropriateness Method. The international consensus panel consisted of patients, family members, community representatives, clinicians, researchers and healthcare quality experts. RESULTS: From an initial 39 unique evidence-based PC-QIs identified and developed, the consensus process yielded 26 final PC-QIs. These included 7 related to structure, 16 related to process, 2 related to outcome and 1 overall global PC-QI. CONCLUSIONS: The final 26 evidence-based and person-informed PC-QIs can be used to measure and evaluate quality incorporating patient perspectives, empowering jurisdictions to monitor healthcare system performance and evaluate policy and practice related to PCC.