The role of placental insufficiency in spontaneous preterm birth: A literature review.

Preterm Birth (delivery before 37 weeks of gestation) is the leading cause of childhood mortality and is also associated with significant morbidity both in the neonatal period and beyond. The aetiology of spontaneous preterm birth is unclear and likely multifactorial incorporating factors such as infection/inflammation and cervical injury. Placental insufficiency is emerging as an additional contributor to spontaneous preterm delivery; however, the mechanisms by which this occurs are not fully understood. Serum biomarkers and imaging techniques have been investigated as potential predictors of placental insufficiency, however none have yet been found to have a sufficient predictive value. This review examines the evidence for the role of the placenta in preterm birth, preterm prelabour rupture of the membranes and abruption as well as highlighting areas where further research is required.

Development of theoretically informed audit and feedback: An exemplar from a complex implementation strategy to improve asthma self-management in UK primary care.

RATIONALE: Audit and feedback is an evidence-based implementation strategy, but studies reporting the use of theory to guide design elements are limited. AIMS AND OBJECTIVES: Within the context of a programme of research aiming to improve the implementation of supported asthma self-management in UK primary care (IMPlementing IMProved Asthma self-management as RouTine [IMP2 ART]), we aimed to design and develop theoretically-informed audit and feedback that highlighted supported asthma self-management provision and areas for improvement in primary care general practices. METHOD: Aligned with the Medical Research Council (MRC) complex intervention framework, the audit and feedback was developed in three phases: (1) Development: literature and theory exploration, and prototype audit and feedback design; (2) Feasibility: eliciting feedback on the audit and feedback from general practice staff (n = 9); (3) Prepiloting: delivering the audit and feedback within the IMP2 ART implementation strategy (incorporating patient and professional resources and an asthma review template) and eliciting clinician feedback (n = 9). RESULTS: Audit and feedback design was guided by and mapped to existing literature suggestions and theory (e.g., Theoretical Domains Framework, Behaviour Change Technique Taxonomy). Feedback on the prototype audit and feedback confirmed feasibility but identified some refinements (a need to highlight supporting self-management and importance of asthma action plans). Prepiloting informed integration with other IMP2 ART programme strategies (e.g., patient resources and professional education). CONCLUSION: We conclude that a multistage development process including theory exploration and mapping, contributed to the design and delivery of the audit and feedback. Aligned with the MRC framework, the IMP2 ART strategy (incorporating the audit and feedback) is now being tested in a UK-wide cluster randomised controlled trial.

IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) in primary care: study protocol for a cluster randomised controlled implementation trial.

BACKGROUND: Asthma is a common long-term condition and major public health problem. Supported self-management for asthma that includes a written personalised asthma action plan, supported by regular professional review, reduces unscheduled consultations and improves asthma outcomes and quality of life. However, despite unequivocal inter/national guideline recommendations, supported self-management is poorly implemented in practice. The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) implementation strategy has been developed to address this challenge. The aim of this implementation trial is to determine whether facilitated delivery of the IMP2ART strategy increases the provision of asthma action plans and reduces unscheduled care in the context of routine UK primary care. METHODS: IMP2ART is a parallel group, cluster randomised controlled hybrid II implementation trial. One hundred forty-four general practices will be randomly assigned to either the IMP2ART implementation strategy or control group. Following a facilitation workshop, implementation group practices will receive organisational resources to help them prioritise supported self-management (including audit and feedback; an IMP2ART asthma review template), training for professionals and resources to support patients to self-manage their asthma. The control group will continue with usual asthma care. The primary clinical outcome is the between-group difference in unscheduled care in the second year after randomisation (i.e. between 12 and 24 months post-randomisation) assessed from routine data. Additionally, a primary implementation outcome of asthma action plan ownership at 12 months will be assessed by questionnaire to a random sub-group of people with asthma. Secondary outcomes include the number of asthma reviews conducted, prescribing outcomes (reliever medication and oral steroids), asthma symptom control, patients' confidence in self-management and professional support and resource use. A health economic analysis will assess cost-effectiveness, and a mixed methods process evaluation will explore implementation, fidelity and adaptation. DISCUSSION: The evidence for supported asthma self-management is overwhelming. This study will add to the literature regarding strategies that can effectively implement supported self-management in primary care to reduce unscheduled consultations and improve asthma outcomes and quality of life. TRIAL REGISTRATION: ISRCTN15448074. Registered on 2 December 2019.

Risk Predictors and Symptom Features of Long COVID Within a Broad Primary Care Patient Population Including Both Tested and Untested Patients.

INTRODUCTION: Symptoms may persist after the initial phases of COVID-19 infection, a phenomenon termed long COVID. Current knowledge on long COVID has been mostly derived from test-confirmed and hospitalized COVID-19 patients. Data are required on the burden and predictors of long COVID in a broader patient group, which includes both tested and untested COVID-19 patients in primary care. METHODS: This is an observational study using data from Platform C19, a quality improvement program-derived research database linking primary care electronic health record data (EHR) with patient-reported questionnaire information. Participating general practices invited consenting patients aged 18-85 to complete an online questionnaire since 7th August 2020. COVID-19 self-diagnosis, clinician-diagnosis, testing, and the presence and duration of symptoms were assessed via the questionnaire. Patients were considered present with long COVID if they reported symptoms lasting ≥4 weeks. EHR and questionnaire data up till 22nd January 2021 were extracted for analysis. Multivariable regression analyses were conducted comparing demographics, clinical characteristics, and presence of symptoms between patients with long COVID and patients with shorter symptom duration. RESULTS: Long COVID was present in 310/3151 (9.8%) patients with self-diagnosed, clinician-diagnosed, or test-confirmed COVID-19. Only 106/310 (34.2%) long COVID patients had test-confirmed COVID-19. Risk predictors of long COVID were age ≥40 years (adjusted Odds Ratio [AdjOR]=1.49 [1.05-2.17]), female sex (adjOR=1.37 [1.02-1.85]), frailty (adjOR=2.39 [1.29-4.27]), visit to A&E (adjOR=4.28 [2.31-7.78]), and hospital admission for COVID-19 symptoms (adjOR=3.22 [1.77-5.79]). Aches and pain (adjOR=1.70 [1.21-2.39]), appetite loss (adjOR=3.15 [1.78-5.92]), confusion and disorientation (adjOR=2.17 [1.57-2.99]), diarrhea (adjOR=1.4 [1.03-1.89]), and persistent dry cough (adjOR=2.77 [1.94-3.98]) were symptom features statistically more common in long COVID. CONCLUSION: This study reports the factors and symptom features predicting long COVID in a broad primary care population, including both test-confirmed and the previously missed group of COVID-19 patients.

Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity.

BACKGROUND: The purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (V̇E/V̇CO2) response during exercise in mild chronic obstructive pulmonary disease (COPD). METHODS: Twenty-nine mild COPD and 19 healthy age-matched control participants undertook lung function testing followed by symptom-limited incremental cardiopulmonary exercise testing . On a separate day, basal (non-chemoreflex) ventilation (V̇EB), the central chemoreflex ventilatory recruitment threshold for CO2 (VRTCO2), and central chemoreflex sensitivity (V̇ES) were assessed using the modified Duffin's CO2 rebreathing method. Resting arterialized blood gas data were also obtained. RESULTS: At standardized exercise intensities, absolute V̇E and V̇E/V̇CO2 were consistently elevated and the end-tidal partial pressure of CO2 was relatively decreased in mild COPD versus controls (all p < 0.05). There were no between-group differences in resting arterialized blood gas parameters, basal V̇E, VRTCO2, or V̇ES (all p > 0.05). CONCLUSION: These data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity.

Swelling among women who need education about leg lymphedema: a descriptive study of lymphedema in women undergoing surgery for endometrial cancer.

OBJECTIVES: In addition to hysterectomy and bilateral salpingo-oophorectomy, comprehensive surgical staging for endometrial cancer includes pelvic and para-aortic lymphadenectomy. Clarifying and addressing the morbidity from these surgical procedures is imperative. The goal of this study was to assess the prevalence of lower extremity swelling after surgery for endometrial cancer. MATERIALS AND METHODS: We performed a descriptive, cross-sectional survey study of women who underwent surgery for endometrial cancer at our institution from 2006 to 2008. Survey information included symptoms, management, and education regarding lymphedema. Demographic information such as race and education was collected in addition to clinical data such as body mass index and age. RESULTS: Of the 482 patients identified, 440 were determined eligible and 305 (69.3%) responded to the survey with information on lower limb swelling (LLS). Of the 108 (35%) responders who reported swelling, only 68 (22%) participants reported a diagnosis of lower limb lymphedema (LLL). The most commonly experienced symptoms among those who reported LLS were tightness, pain/tenderness, and heaviness. Among those with a diagnosis of LLL, most (60%) stated it affected their daily activities and noted exacerbating factors such as prolonged standing, heat, and walking. The most common therapies used to reduce symptoms included leg elevation (96%), compression stockings (65%), diuretics (46%), massage therapy (35%), and bandaging (25%). There was no association between LLS or LLL diagnosis and body mass index, age, race, and tobacco use. Only 8% of responders reported receiving preoperative education regarding risks for LLS and a desire for more comprehensive education was frequently noted. CONCLUSIONS: The patient-reported incidence of LLS occurred in approximately 35% of survey participants who underwent surgery for endometrial cancer. However, only 22% reported a diagnosis of LLL. Efforts to obtain the true incidence of LLL and to develop effective educational materials and programs to improve the management of lymphedema are warranted.

Impact of pulmonary rehabilitation on the major dimensions of dyspnea in COPD.

The evaluation of dyspnea and its responsiveness to therapy in COPD should consider the multidimensional nature of this symptom in each of its sensory-perceptual (intensity, quality), affective and impact domains. To gain new insights into mechanisms of dyspnea relief following pulmonary rehabilitation (PR), we examined effects on the major domains of dyspnea and their interaction with physiological training effects. This randomized, controlled study was conducted in 48 subjects with COPD. Subjects received either 8-weeks of PR or usual care (CTRL). Pre- and post-intervention assessments included: sensory-perceptual (i.e., exertional dyspnea intensity, dyspnea descriptors at end-exercise), affective (i.e., intensity of breathing-related anxiety during exercise, COPD self-efficacy, walking self-efficacy) and impact (i.e., activity-related dyspnea measured by the Baseline/Transition Dyspnea Index, Chronic Respiratory Questionnaire dyspnea component, St. George's Respiratory Disease Questionnaire activity component) domains of dyspnea; functional performance (i.e., 6-minute walk, endurance shuttle walk); pulmonary function; and physiological measurements during constant work rate cycle exercise at 75% of the peak incremental work rate. Forty-one subjects completed the study: PR (n = 17) and CTRL (n = 24) groups were well matched for age, sex, body size and pulmonary function. There were no significant between-group differences in pre- to post-intervention changes in pulmonary function or physiological parameters during exercise. After PR versus CTRL, significant improvements were found in the affective and impact domains but not in the sensory-perceptual domain of dyspnea. In conclusion, clinically meaningful improvements in the affective and impact domains of dyspnea occurred in response to PR in the absence of consistent physiological training effects.

Neuroendocrine carcinoma of the uterine cervix: the role of multimodality therapy in early-stage disease.

BACKGROUND: Neuroendocrine carcinomas (NECs) of the cervix comprise only 2% of all cervical cancers. Prospective data is limited and treatment guidelines rely on retrospective reviews and literature from lung NEC. The objective of this study was to report our experience in the management of this rare disease. METHODS: This was an IRB-approved retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990 and 2012. Demographic, treatment and survival data was collected. Progression free survival (PFS) and overall survival (OS) were assessed. RESULTS: Twenty-six patients met inclusion criteria. Advanced-stage disease (II-IV) was diagnosed in 58% (n=15) of patients. Of the eleven patients with stage I disease, five were treated with platinum-based neoadjuvant chemotherapy (NACT), six with initial radical surgery, and seven received adjuvant therapy including chemotherapy and/or radiation. Nine patients (82%) are currently without evidence of disease (NED). Patients with stage I disease had significantly improved PFS and OS compared to stages II-IV with a median OS that was not reached and 12.1 months, respectively (p=0.0013). The majority of stage I patients with lymph node metastasis and large tumors achieved durable remission with triple-modality therapy including NACT and surgery followed by adjuvant therapy. CONCLUSIONS: Cervical NEC is an aggressive disease associated with a high mortality rate. Patients with advanced-stage disease have a poor prognosis regardless of therapy. However, multimodality with consideration of triple-modality therapy in early-stage disease has the potential for complete response and long-term survival, supporting the goal of curative intent in these patients.

Effect of adjunct fluticasone propionate on airway physiology during rest and exercise in COPD.

RATIONALE: Combination therapy with corticosteroid and long-acting ß(2)-agonists (LABA) in a single inhaler is associated with superior effects on airway function and exercise performance in COPD compared with LABA monotherapy. The physiological effects of adding inhaled corticosteroid monotherapy to maintenance bronchodilator therapy (long-acting anticholinergics and LABA singly or in combination) in COPD are unknown. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study (NCT00387036) to compare the effects of inhaled fluticasone propionate 500 µg (FP500) twice-daily and placebo (PLA) on airway function during rest and exercise, measured during constant work rate cycle exercise at 75% of maximum incremental cycle work rate, in 17 patients with COPD (FEV(1) ≤ 70% predicted). RESULTS: After treatment with FP500 compared to PLA, there were significant increases in post-dose measurements of FEV(1) (+115 mL, P = 0.006) and the FEV(1)/FVC ratio (+2.5%, P = 0.017), along with decreases in plethysmographic residual volume (-0.32L; P = 0.031), functional residual capacity (-0.30L, P = 0.033), and total lung capacity (-0.30L, P = 0.027) but no changes in vital capacity or inspiratory capacity (IC). Post-treatment comparisons demonstrated a significant improvement in endurance time by 188 ± 362 s with FP500 (P = 0.047) with no concomitant increase in dyspnea intensity. End-inspiratory and end-expiratory lung volumes were reduced at rest and throughout exercise with FP500 compared with PLA (P < 0.05). CONCLUSION: Inhaled FP500 monotherapy was associated with consistent and clinically important improvements in FEV(1), static lung volumes, dynamic operating lung volumes, and exercise endurance when added to established maintenance long-acting bronchodilator therapy in patients with moderate to severe COPD.

Effect of obesity on respiratory mechanics during rest and exercise in COPD.

The presence of obesity in COPD appears not to be a disadvantage with respect to dyspnea and weight-supported cycle exercise performance. We hypothesized that one explanation for this might be that the volume-reducing effects of obesity convey mechanical and respiratory muscle function advantages. Twelve obese chronic obstructive pulmonary disease (COPD) (OB) [forced expiratory volume in 1 s (FEV(1)) = 60%predicted; body mass index (BMI) = 32 ± 1 kg/m(2); mean ± SD] and 12 age-matched, normal-weight COPD (NW) (FEV(1) = 59%predicted; BMI = 23 ± 2 kg/m(2)) subjects were compared at rest and during symptom-limited constant-work-rate exercise at 75% of their maximum. Measurements included pulmonary function tests, operating lung volumes, esophageal pressure, and gastric pressure. OB vs. NW had a reduced total lung capacity (109 vs. 124%predicted; P < 0.05) and resting end-expiratory lung volume (130 vs. 158%predicted; P < 0.05). At rest, there was no difference in respiratory muscle strength but OB had greater (P < 0.05) static recoil and intra-abdominal pressures than NW. Peak ventilation, oxygen consumption, and exercise endurance times were similar in OB and NW. Pulmonary resistance fell (P < 0.05) at the onset of exercise in OB but not in NW. Resting inspiratory capacity, dyspnea/ventilation plots, and the ratio of respiratory muscle effort to tidal volume displacement were similar, as was the dynamic performance of the respiratory muscles including the diaphragm. In conclusion, the lack of increase in dyspnea and exercise intolerance in OB vs. NW could not be attributed to improvement in respiratory muscle function. Potential contributory factors included alterations in the elastic properties of the lungs, raised intra-abdominal pressures, reduced lung hyperinflation, and preserved inspiratory capacity.

Effect of menopause on the chemical control of breathing and its relationship with acid-base status.

This study examined the role of alterations in the chemoreflex control of breathing, acid-base balance, and their interaction in postmenopausal ventilatory adaptations. A modified iso-oxic hyperoxic and hypoxic CO(2)-rebreathing procedure was employed to evaluate central and peripheral chemoreflex drives to breathe, respectively, in 15 healthy postmenopausal and 20 premenopausal women of similar age. Arterialized venous blood samples were collected at rest for the estimation of arterial Pco(2) (Pa(CO(2))) and H(+) concentration ([H(+)]), plasma strong ion difference ([SID]) and total weak acid ([A](tot)) concentrations, and serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations. In post- compared with premenopausal women, Pa(CO(2)), [SID], and the central chemoreflex ventilatory recruitment threshold for Pco(2) (VRTco(2)) were higher, whereas [P(4)] and [E(2)] were lower (all P < 0.05), with no significant change in central or peripheral chemoreflex sensitivity, peripheral chemoreflex VRTco(2), and [A](tot). The acidifying effect of an increased Pa(CO(2)) was offset by the alkalizing effect of an increased [SID], such that [H(+)] was preserved in post- compared with premenopausal women. Pa(CO(2)) correlated positively with the central chemoreflex VRTco(2) (r = 0.67, P < 0.01), which in turn correlated positively with [SID] (r = 0.53, P < 0.01) within the pooled data. In conclusion, the relative alveolar hypoventilation and attendant arterial hypercapnia in healthy post- compared with premenopausal women could be explained, in part, by the interaction of 1) reduced central, but not peripheral, chemoreflex VRTco(2), 2) increased [SID], and 3) reduced circulating female sex steroid hormone concentrations.