Global consensus process to establish a core dataset for hidradenitis suppurativa registries.

BACKGROUND: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. OBJECTIVES: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. METHODS: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. RESULTS: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. CONCLUSIONS: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.

High Unemployment Rate in Patients with Hidradenitis Suppurativa despite High Educational Attainment.

BACKGROUND: Hidradenitis suppurativa (HS) is associated with lower socioeconomic status (SES). The adverse influence of HS on education and employment may explain this. It remains unknown whether HS causes downward social trajectories, i.e., social drift, or whether those affected are born into a lower SES. We aimed to assess the influence of HS on education and employment and compare the highest educational attainment of participants with their parents. METHODS: An anonymous online survey was distributed by patient-led organisations. Frequencies were compared with χ2 and disease interactions with one-way ANOVA. RESULTS: Among 335 respondents from 10 countries, 94.9% completed secondary/high school, 71.3% completed further education, 41.8% completed an undergraduate degree, 20% completed postgraduate education, 10.7% completed a masters, and 2.1% completed a doctorate. Participant education was greater than parental education (p < 0.001). Despite this, 24.2% were unemployed and 15.2% were receiving illness benefit. Compared to national statistics, HS participants from Ireland (p = 0.003), the USA (p < 0.001), and the UK (p < 0.001) were more likely to be unemployed/receiving illness benefit despite higher educational attainment in Ireland (p = 0.006) and the USA (p = 0.003) with similar education in the UK (p = 0.153). CONCLUSIONS: Social drift describes downward social trajectories due to the development of a disease. Participants in this study report greater education than their parents and the background population, but despite this, they are experiencing downward social trajectories with higher unemployment and receipt of illness benefit. Disease onset in HS tends to be at peak educational age. Education does not appear to be impaired by early disease with disease accumulation during employment years limiting opportunities.

The Personal Impact of Daily Wound Care for Hidradenitis Suppurativa.

BACKGROUND: Recurring nodules, abscesses, and lesions characterise hidradenitis suppurativa (HS): a chronic, inflammatory skin disorder. Globally the prevalence of HS is estimated to be around 1% of the population. Leakage, pain, and odour from HS wounds require substantial management. Little is known of the personal burdens that routine wound management imposes on the patient. OBJECTIVES: To evaluate how routine HS wound management impacts patients in terms of the time spent changing dressings, the number of dressings required per day, pain experienced during dressing changes, and negative impact on various domains of their personal lives. METHODS: An anonymous online questionnaire was posted on closed social media patient support groups between April and May 2019. Pearson χ2 test was used to evaluate if Hurley stages influenced the personal impact of wound care routines on patients. Statistical significance was determined as p value <0.05. RESULTS: In total, 908 people from 28 countries responded. Of these, 81% (n = 734) reported that regular dressing changes negatively impacted on their quality of life. Most patients, 82% (n = 744), experience pain during dressing changes. 16% (n = 142) of patients required five or more dressings daily, and 12% (n = 108) spend over 30 min daily tending to wounds. Patients indicated high levels of dissatisfaction with currently available wound dressings. CONCLUSION: HS wound management imposes a substantial personal burden on patients. There is a clear unmet need for HS-specific wound dressings and wound care provisions, and a greater awareness of the condition and its impact is needed among clinicians.

Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement.

BACKGROUND: Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator's role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. METHODS: An extensive literature review was conducted to identify i) information substantiating specific components of an educator's role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. RESULTS: The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator's role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. CONCLUSIONS: This research clarifies the distinct elements of an educator's role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance.

How to measure home blood pressure: Recommendations for healthcare professionals and patients.

BACKGROUND: Home blood pressure (BP) monitoring is the self-measurement of BP in the home environment. It is complementary to 24-hour ambulatory BP, for better diagnosis and management of patients with high BP. Home BP monitoring is in widespread use, but variation in monitoring protocols could lead to inaccurate assessment of BP. OBJECTIVE: The aim of this article is to provide a practical guide (with resources) for patients and doctors on how to measure home BP according to a standardised, evidence-based protocol. DISCUSSION: Home BP should be measured using a validated, automatic BP device (preferably with memory storage), using an appropriately sized upper arm cuff. Measurements should be taken after five minutes of seated rest and before medication, food or vigorous exercise. BP should be recorded for seven days (five days minimum) in the morning and evening (two readings each). Overall, home BP is the average systolic and diastolic BP over seven days (excluding the first day); an average of ≥135/85 mmHg is indicative of hypertension.

Home monitoring of blood pressure.

Home blood pressure monitoring is the self-measurement of blood pressure by patients. In the diagnosis and management of high blood pressure it is complementary to 24-hour ambulatory blood pressure monitoring and clinic blood pressure measurements. Home monitoring can also help to identify white-coat and masked hypertension. Home monitoring has good reproducibility, is well tolerated and relatively inexpensive. It is superior to blood pressure taken in the clinic in predicting cardiovascular events and mortality. Twice-daily measurements are recommended, usually in the morning and evening for a minimum of five days. The threshold for defining hypertension is an average home blood pressure of 135/85 mmHg or above. Patients are engaged with their management when they monitor their own blood pressure. This results in increased adherence to therapy and lower blood pressure.

White-coat hypertension.

1. Numerous studies have examined whether white-coat hypertension (WCHT) is associated with increased cardiovascular risk, but with definitions of WCHT that were not sufficiently robust, results have been inconsistent. The aim of the present review was to standardize the evidence by only including studies that used a definition of WCHT consistent with international guidelines. 2. Published studies were reviewed for data on vascular dysfunction, target organ damage, risk of future sustained hypertension and cardiovascular events. 3. White-coat hypertension has a population prevalence of approximately 15% and is associated with non-smoking and slightly elevated clinic blood pressure. Compared with normotensives, subjects with WCHT are at increased cardiovascular risk due to a higher prevalence of glucose dysregulation, increased left ventricular mass index and increased risk of future diabetes and hypertension. 4. In conclusion, management of a patient with WCHT should focus on cardiovascular risk factors, particularly glucose intolerance, not blood pressure alone.

Changes in the diameter and valve closure time of leg veins across the menstrual cycle.

OBJECTIVES: The purpose of this study was to determine the changes (if any) in the diameter and valve closure time of the lower limb veins in healthy young nulliparous women at different phases of the menstrual cycle. METHODS: Fifty-three young nulliparous women were asked to undergo clinical evaluations and duplex ultrasound examinations of both lower limb veins to monitor changes in the vein diameter and valve closure time at different phases of their menstrual cycles. The vein diameter on B-mode imaging and valve closure time on pulsed Doppler tracing were calculated at days 1 to 4, 14 to 16, and 25 to 28 of the menstrual cycle. Freidman and related samples Wilcoxon signed rank tests were used to determine time-related changes in venous function. RESULTS: The volunteers' mean age ± SD was 20.60 ± 1.90 years, and their mean body mass index was 23.90 ± 4.90 kg/m(2). There was a gradual increase in the vein diameter and valve closure time at the specified phases of the menstrual cycle. Friedman and related samples Wilcoxon signed rank tests for venous segment diameter and valve closure time changes between the different phases of the menstrual cycle were performed and showed statistical significance for each venous segment within each limb (P = .003-.025). Also, when adjusted for body mass index, statistical significance existed for the same venous segments in the same limbs (P =.001-.049). There was no statistical significance for the same venous segments at the same phase of the menstrual cycle between limbs (related samples Wilcoxon signed rank test: P =.079-.97). CONCLUSIONS: During the menstrual cycle, the lower limb veins show an increase in their diameter and valve closure time. These changes are probably mediated by the female sex hormones.

Wound drainage measurements: a narrative review.

Drainage from chronic wounds can significantly negatively impact a patient's quality of life. Change in severity of wound drainage is an important measure of treatment efficacy for wounds. This study reviews existing tools used to assess wound drainage. Qualitative drainage tools are overall less burdensome, and however, differences in user interpretation may reduce inter-rater reliability. Quantitative drainage tools enable more reliable comparisons of drainage severity and treatment response between patients but sometimes require equipment to administer, increasing responder burden. Gaps in the current wound drainage measurement landscape are highlighted. Many of the existing scales have not been validated in robust studies. There is also a lack of validated global drainage measurement tools for patients with chronic inflammatory skin disorders with drainage, such as hidradenitis suppurativa or pyoderma gangrenosum. Development of a succinct drainage measurement tool for inflammatory skin diseases where drainage is a prominent symptom will improve monitoring of meaningful treatment response.

Moderate morning rise in blood pressure has lowest risk of stroke but only in women.

BACKGROUND: The morning period which is recognized as the highest risk for cardiovascular events is associated with a surge in blood pressure (BP). However, it is unclear what aspect of this rise is important. AIM: To determine whether the rate of rise (RoR), the magnitude (day night difference) or the product [BP power (BPPower)] is associated with increased cardiovascular risk. METHODS: We developed a logistic equation method to fit individual 24-h patterns of BP to determine RoR, amplitude and BPPower using the ambulatory recordings from the Ohasama study including 564 men and 971 women (16.6 years follow-up). RESULTS: Men had a higher risk of cardiovascular events than women (24, 16%, P < 0.001). Age and night BP were strong linear risk predictors. In men sorting risk by quintiles of BPPower (adjusted for age, night BP, smoking status) revealed no clear linear or nonlinear pattern. However, in women BPPower had a U-shaped relationship with the lowest risk being the 2-3rd quintile for all cardiovascular events (Pquadratic = 0.01) including cardiovascular death (Pquadratic = 0.03) and nonfatal stroke (Pquadratic = 0.02). A similar but less clear trend was observed with the RoR but only stroke (infarct) reached significance (Pquadratic = 0.03) while sorting by range showed a U shaped pattern for combined cardiovascular events (Pquadratic = 0.04). CONCLUSION: These findings suggest that the morning BPPower is an important independent risk factor for predicting cardiovascular events and stroke but only in women with median levels having the lowest risk.

Mechanical and circulating biomarkers in isolated clinic hypertension.

1. This review examines the current evidence for altered mechanical and circulating biomarkers in isolated clinic hypertension and their potential significance. 2. Arterial stiffness, as assessed by central pulse wave velocity, is influenced by multiple cardiovascular risk factors; however, an independent association with isolated clinic hypertension (ICHT) has not been convincingly shown in four small studies. 3. Endothelial dysfunction, as assessed by brachial artery flow-mediated vasodilation, circulating levels of endothelial markers (e.g. nitrite/nitrate, von Willebrand factor, endothelin-1) and/or circulating levels of inhibitors of vascular nitric oxide (plasma asymmetric dimethylarginine, homocysteine), has been shown to be present in established hypertension and to a variable and inconsistent extent in subjects with ICHT. 4. Evidence of increased oxidative stress in ICHT versus normotensive subjects was found in two of three studies. 5. Circulating inflammatory markers C-reactive protein and plasminogen activator inhibitor-1 were significantly increased in two of three and two of two studies, respectively, in ICHT compared with normotensive subjects. 6. Urinary albumin excretion is a marker of both arterial and renal disease. The consensus from seven studies in patients with ICHT is that albuminuria is not an independent marker for ICHT. 7. Studies to date assessing biomarkers in ICHT have been small and cross-sectional. Larger, long-term longitudinal studies of arterial functional and circulating biomarkers are required to assess the potential vascular impact of ICHT.

Novel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM Study.

BACKGROUND: To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD). METHODS: Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye. RESULTS: 160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46). CONCLUSION: The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.

Association of carotid intima-medial thickness and indices of arterial stiffness with cardiovascular disease outcomes in CKD.

BACKGROUND: Indices of arterial structure and stiffness are proposed as surrogate markers of cardiovascular disease in patients with chronic kidney disease (CKD), but no study examined multiple markers in the same population. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 315 subjects with stages 4 to 5 CKD, aged 24 to 79 years (mean age, 56.6 +/- 13.6 [SD] years), enrolled in the Atherosclerosis and Folic Acid Supplementation Trial. PREDICTORS: Carotid arterial intima-medial thickness (IMT; n = 315) and indices of arterial stiffness (n = 207), including aortofemoral pulse wave velocity (PWV[a-f]), systemic arterial compliance (SAC), and carotid-derived augmentation index. OUTCOMES: The primary outcome was a composite of all fatal and nonfatal cardiovascular events. RESULTS: During follow-up (median, 3.6 years), 95 cardiovascular events occurred. On Cox proportional-hazard modeling, mean maximum IMT, PWV(a-f), and SAC were predictive of the composite clinical end point of all cardiovascular events, but carotid-derived augmentation index was not (hazard ratio [HR] for every 0.01-mm increase in IMT, 1.09; P = 0.001; 95% confidence interval [CI], 1.03 to 1.14; HR for every 1-m/s increase in PWV(a-f), 1.18; P < 0.001; 95% CI, 1.12 to 1.25; HR for every 0.01-U/mm Hg decrease in SAC, 0.98; P = 0.01; 95% CI, 0.97 to 0.99). After adjustment for age, sex, blood pressure, diabetes, past cardiovascular disease, cholesterol level, and smoking, PWV(a-f) remained a significant independent predictor of cardiovascular events (adjusted HR, 1.12; P = 0.001; 95% CI, 1.05 to 1.20), but IMT and SAC did not. LIMITATIONS: Study power to analyze differences between predialysis and dialysis stages of CKD. CONCLUSIONS: PWV(a-f) is the only arterial index independently associated with cardiovascular outcome in patients with CKD.

Relationship of waist and hip circumference with coagulation and fibrinolysis in postmenopausal women.

The contribution of obesity to the occurrence of cardiovascular events may not be wholly related to its influence on traditional risk factors. Coagulation and fibrinolysis may also influence cardiovascular risk, but the relationship of adiposity with these processes is unclear. The aim of the present study was to investigate the relationships of BMI (body mass index), waist circumference, hip circumference and WHR (waist-to-hip ratio) with VIIc (factor VII activity), plasma markers of thrombin generation [F1+2 (prothrombin fragment 1+2)], fibrin formation [SF (soluble fibrin)] and fibrin turnover (D-dimer), and PAI-1 (plasminogen activator inhibitor-1; a marker of fibrinolytic inhibitory capacity). The study cohort was 80 healthy postmenopausal women who were not diabetic, current smokers or taking hormone therapy and who had a fasting sample of blood collected. VIIc, F1+2, SF and PAI-1 were all positively correlated with BMI, waist circumference and WHR, whereas D-dimer was positively correlated with waist circumference and WHR, but not BMI. WHR was the strongest correlate of all the markers except for PAI-1, which was most closely related to BMI. Hip circumference became a negative correlate of F1+2 and D-dimer after adjusting for waist circumference. The relationships of WHR with F1+2 and SF, but not with VIIc and D-dimer, were independent of traditional risk factors. The positive association between waist circumference and markers of thrombin generation, fibrin production and fibrin turnover suggests that abdominal adiposity may contribute to atherothrombosis by activating intravascular coagulation. In contrast, a larger hip circumference appears to have a protective affect against coagulation activation.

The orf4 gene of the enterobacterial ICE, R391, encodes a novel UV-inducible recombination directionality factor, Jef, involved in excision and transfer of the ICE.

The enterobacterial mobile genetic element R391, the prototype ICE (integrating-conjugative element) of the SXT/R391 family, shows increased conjugative transfer following UV irradiation. This is dependent on a functioning R391 orf4 gene, which is adjacent to the element encoded integrase gene, int. orf4 mutants fail to form a detectable circular transfer intermediate, do not show UV induced transfer and show a much reduced general transfer ability. The orf4 gene product, termed Jef (IncJ excision factor), shows little homology to anything currently in the nucleotide or protein databases. It is predicted to encode a 66 amino acid, 8.03 kDa, basic, DNA-binding protein with an iso-electric point of pH 8.1: these characteristics being similar to those of recombinational directionality factors involved in excision. Jef expression is up-regulated upon UV irradiation as demonstrated by real-time reverse transcriptase PCR and is controlled by two element encoded genes orf90 and orf91, which show similarity to the transcriptional activator complex FlhC and FlhD. orf4, orf90 and orf91 are conserved in all the SXT/R391-like elements sequenced to date including SXT, ICESpuPO1 and ICEVchMex1. orf4 is also conserved in other SXT/R391 family members such as R997, R392, R705 and pMERPH as shown by sequencing amplicons from these ICEs generated using orf4 specific primers.

Molecular tools to detect the IncJ elements: a family of integrating, antibiotic resistant mobile genetic elements.

The IncJ group of enterobacterial mobile genetic elements, which include R391, R392, R705, R997 and pMERPH, have been shown to be site-specific integrating elements encoding variable antibiotic and heavy metal resistance genes. They insert into a specific 17-bp site located in the prfC gene, encoding peptide release factor 3, in Escherichia coli and other hosts. A key feature of known IncJ elements is the presence of a site-specific recombination module consisting of an attachment site on the element and an integrase-encoding gene of the tyrosine recombinase class, which promotes integration between the attachment site on the element and a similar site on the host chromosome. We have cloned and sequenced the integrases from a number of known IncJ elements and designed PCR primers for specific amplification of this gene. Using conserved regions of enterobacterial prfC genes upstream and downstream of the insertion site, and conserved sequences at the ends of the integrated IncJ elements, we have designed specific primers to amplify across the integrated IncJ attL and attR junction fragments. Alignment of over 30 enterobacterial prfC-like genes indicates that the primers designed to amplify attR junction would amplify IncJ element: host junctions from a wide variety of hosts. The IncJ elements have been shown to sensitise recA(+)E. coli K12 strains to UV irradiation. A simple and rapid procedure for demonstrating this effect is described. These tools should enable the rapid detection of such elements in clinical and environmental settings.