Ultraviolet radiation exposure to the face in patients with xeroderma pigmentosum and healthy controls: applying a novel methodology to define photoprotection behaviour.

BACKGROUND: In xeroderma pigmentosum (XP), the main means of preventing skin and eye cancers is extreme protection against ultraviolet radiation (UVR). Protection is most important for the face. OBJECTIVES: We aimed to assess how well patients with XP adhere to medical advice to protect against UVR by objectively estimating the mean daily dose of UVR to the face. METHODS: We objectively estimated the UVR dose to the face in 36 patients with XP and 25 healthy individuals over 3 weeks in the summer. We used a new methodology which combined UVR dose measurements from a wrist-worn dosimeter with an activity diary record of face photoprotection behaviour for each 15-min period spent outside. A protection factor was associated with each behaviour, and the data were analysed using a negative binomial mixed-effects model. RESULTS: The mean daily UVR dose (weighted for DNA damage capacity) to the face in the patients with XP was 0·13 standard erythemal doses (SEDs) (mean in healthy individuals = 0·51 SED). There was wide variation between patients (range < 0·01-0·48 SED/day). Self-caring adult patients had a very similar UVR dose to the face as cared-for patients (0·13 vs. 0·12 SED/day), despite photoprotecting much more poorly when outside, because the self-caring adults were outside in daylight much less. CONCLUSIONS: Photoprotection behaviour varies widely within the XP group indicating that nonadherence to photoprotection advice is a significant issue. The timing and duration of going outside are as important as photoprotective measures taken when outside, to determine the UVR exposure to the face. This new methodology will be of value in identifying the sources of UVR exposure in other conditions in which facial UVR exposure is a key outcome, particularly in patients with multiple nonmelanoma skin cancers.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

To what extent do disease severity and illness perceptions explain depression, anxiety and quality of life in hidradenitis suppurativa?

BACKGROUND: Hidradenitis suppurativa (HS) can have significant psychological consequences and affect quality of life (QoL). This has been associated with disease severity. However, it has not been established whether these effects are more strongly related to the severity of the disease, as rated by the clinician, or to the patient's perception of their condition. OBJECTIVES: To examine the relationships between disease severity and illness perceptions, and depression, anxiety and QoL in HS. METHODS: This study was cross-sectional in design. In total, 211 patients with HS completed the Brief Illness Perception Questionnaire (BIPQ), the Patient's Health Questionnaire-2 (PHQ-2), the Generalized Anxiety Disorder-2 (GAD-2) and the Dermatology Life Quality Index (DLQI). HS severity was assessed by the clinician, using the Hurley staging system. RESULTS: Patients with HS perceived their condition as chronic - having many symptoms, severe consequences and a negative emotional influence - and felt low personal control over their illness. Self-reports showed significant levels of depression, anxiety and impaired QoL, which were strongly associated with illness perceptions. Hierarchical regression analyses revealed that illness perceptions explained a much greater proportion of variance in depression, anxiety and QoL than the traditional explanatory variable, disease severity. CONCLUSIONS: HS can severely impair psychological well-being and QoL, which are more strongly associated with the person's beliefs about their illness than clinicians' severity assessments. Therefore, illness perceptions may be useful in the routine assessment of patients with HS and may provide a strong basis for interventions aimed at improving their psychological well-being and QoL.

Improving medication adherence in rheumatoid arthritis (RA): a pilot study.

The aim of this exploratory pilot study was to adapt a psychological intervention to improve adherence to medication for patients with rheumatoid arthritis (RA). The approach draws on cognitive behavioural therapy (CBT) techniques, including motivational interviewing . The current study aimed to (i) adapt the intervention for patients with RA, (ii) assess its effectiveness in improving adherence to medication and (iii) evaluate patients' experience of the intervention. Participants were randomly allocated to either the 'intervention group' (N = 10), receiving up to six weekly sessions of 'Compliance Therapy', or to the 'wait-list control' group (N = 8), who received standard care. Data was collected pre intervention (baseline), post intervention and at six weeks post intervention (follow-up). Eighteen female participants with a mean age of 48.78 years (SD 15.12) took part in the study. Comparisons across the two time points for each group found that only those in the 'intervention' group demonstrated significant improvement in mean scores on adherence measures. Between-group comparisons were not significant. The pilot study suggests that an intervention based on CBT may improve adherence in patients with RA, but further research is required.

Management of osteoporosis of the oldest old.

UNLABELLED: This consensus article reviews the diagnosis and treatment of osteoporosis in geriatric populations. Specifically, it reviews the risk assessment and intervention thresholds, the impact of nutritional deficiencies, fall prevention strategies, pharmacological treatments and their safety considerations, the risks of sub-optimal treatment adherence and strategies for its improvement. INTRODUCTION: This consensus article reviews the therapeutic strategies and management options for the treatment of osteoporosis of the oldest old. This vulnerable segment (persons over 80 years of age) stands to gain substantially from effective anti-osteoporosis treatment, but the under-prescription of these treatments is frequent. METHODS: This report is the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores some of the reasons for this and presents the arguments to counter these beliefs. The risk assessment of older individuals is briefly reviewed along with the differences between some intervention guidelines. The current evidence on the impact of nutritional deficiencies (i.e. calcium, protein and vitamin D) is presented, as are strategies to prevent falls. One possible reason for the under-prescription of pharmacological treatments for osteoporosis in the oldest old is the perception that anti-fracture efficacy requires long-term treatment. However, a review of the data shows convincing anti-fracture efficacy already by 12 months. RESULTS: The safety profiles of these pharmacological agents are generally satisfactory in this patient segment provided a few precautions are followed. CONCLUSION: These patients should be considered for particular consultation/follow-up procedures in the effort to convince on the benefits of treatment and to allay fears of adverse drug reactions, since poor adherence is a major problem for the success of a strategy for osteoporosis and limits cost-effectiveness.

Patients' beliefs about the causes, persistence and control of psychotic experiences predict take-up of effective cognitive behaviour therapy for psychosis.

BACKGROUND: There is evidence that patients with schizophrenia benefit from standard cognitive behaviour therapy (CBT) only if active techniques are used ('full therapy'). By contrast, attending sessions but not proceeding beyond engagement and assessment strategies ('partial therapy'), or simply not attending sessions ('no therapy'), is not associated with better outcomes. The factors leading to full therapy are unknown. We hypothesized that patients' initial ideas about the nature and extent of their problems would predict use of CBT. A match between patients' views of their problems and the principles underlying treatment would lead to better outcomes. METHOD: Ninety-two patients with a recent relapse of psychosis completed the Illness Perception Questionnaire (IPQ) before receiving CBT. We examined whether their illness perceptions predicted the take-up of therapy. RESULTS: Patients who did not attend sessions believed their problems would not last as long as those who attended them. Those who attended sessions but did not proceed to full therapy had a lower sense of control over their problems and a more biological view of their causes. Patients who took up full therapy were more likely to attribute the cause of their problems to their personality and state of mind. The take-up of therapy was predicted neither by levels of psychiatric symptoms nor by insight. CONCLUSIONS: People with psychosis who have psychologically orientated views of their problems, including the potential to gain control over them, may be more likely to engage fully and do well with standard CBT for psychosis, irrespective of the severity of their problems.

Feedback of personal retinal images appears to have a motivational impact in people with non-proliferative diabetic retinopathy and suboptimal HbA1c: findings of a pilot study.

AIM: To conduct a pilot study to explore the potential impact of visual feedback of personal retinal images on diabetes outcomes. METHODS: Twenty-five participants with non-proliferative diabetic retinopathy and suboptimal HbA(1c) (> 53 mmol/mol; > 7%) were randomized to receive visual feedback of their own retinal images or to a control group. At baseline and 3-month follow-up, HbA(1c), standard measures of beliefs, diabetes-related distress and self-care activities were assessed. RESULTS: In unadjusted models, relative to controls, the intervention group showed significantly greater improvement in HbA(1c) at 3-month follow-up (-0.6% vs. +0.3%, P < 0.01), as well as enhanced motivation to improve blood glucose management (P < 0.05). CONCLUSIONS: This small pilot study provides preliminary evidence that visual feedback of personal retinal images may offer a practical educational strategy for clinicians in eye care services to improve diabetes outcomes in non-target compliant patients. A fully powered randomized controlled trial is required to confirm these findings and determine the optimal use of feedback to produce sustained effects.

Do behaviour-change techniques contribute to the effectiveness of exercise therapy in patients with intermittent claudication? A systematic review.

This systematic narrative review of randomised controlled trials (RCTs) identifies and evaluates the efficacy of behaviour-change techniques explicitly aimed at walking in individuals with intermittent claudication. An electronic database search was conducted up to December 2012. RCTs were included comparing interventions incorporating behaviour-change techniques with usual care, walking advice or exercise therapy for increasing walking in people with intermittent claudication. Studies were evaluated using the Cochrane Collaboration risk of bias tool. The primary outcome variable was maximal walking ability at least 3 months after the start of an intervention. Secondary outcome variables included pain-free walking ability, self-report walking ability and daily walking activity. A total of 3,575 records were retrieved. Of these, six RCTs met the inclusion criteria. As a result of substantial heterogeneity between studies, no meta-analysis was conducted. Overall, 11 behaviour-change techniques were identified; barrier identification with problem solving, self-monitoring and feedback on performance were most frequently reported. There was limited high-quality evidence and findings were inconclusive regarding the utility of behaviour-change techniques for improving walking in people with intermittent claudication. Rigorous, fully powered trials are required that control for exercise dosage and supervision in order to isolate the effect of behaviour-change techniques alongside exercise therapy.

Treated unicameral bone cysts.

Unicameral bone cysts (UBCs) are a common benign entity involving the metaphysis of growing bone, occurring within the first two decades of life. Assessment of these lesions, both before and after surgery, is performed routinely utilizing radiographs. We present a review of UBCs at various stages of treatment, including both successful and incomplete healing, and describe the imaging findings throughout their postoperative course.

'Why, why did you have me treated?': the psychotic experience in a literary narrative.

In this paper, the authors suggest an approach that may be helpful in teaching medical humanities to medical students. In the context of an honours class on medicine and literature, students (1) read a novel on an illness, (2) interviewed a patient with the medical condition described in the novel and (3) wrote an essay on the biomedical, narrative and literary aspects of these sources of information. The authors compared the story of Chekhov's literary protagonist Kovrin in The Black Monk with the personal story of patient H., who was diagnosed with schizophrenia. The narratives of the two patients were compared, based on Chekhov's literary narrative and the narrative of the patient. Both patients appeared to somehow regret losing their symptoms, following various psychiatric treatments. Both narratives show the ambivalence between the gain and loss that adequate psychiatric treatment may bring. Studying novels and other literary sources may help in understanding the story of the patient better, with associated improvements in various aspects of medical outcome. Reading literary fiction may help to increase an understanding of patients' emotions, experiences, cognitions and perspectives. It may also reduce the emotional distance between the self and the patient. The educational approach that was explored in the authors' honours class may be helpful to others when developing methods for teaching medical humanities to (medical) students.

Coping style and depression influence the healing of diabetic foot ulcers: observational and mechanistic evidence.

AIMS/HYPOTHESIS: Experimental evidence suggests that the healing of diabetic foot ulcers is affected by psychosocial factors such as distress. We examined this proposal in a prospective study, in which we considered the role of psychological distress and coping style in the healing of diabetic foot ulcers over a 24 week period. We also explored the role of salivary cortisol and matrix metalloproteinases (MMPs) as potential mechanisms. METHODS: For this prospective observational study we recruited 93 (68 men; mean age 60 years) patients with neuropathic or neuroischaemic diabetic foot ulcers from specialist podiatry clinics in secondary care. Clinical and demographic determinants of healing, psychological distress, coping, salivary cortisol and both MMP2 and MMP9 were assessed at baseline. Ulcers were assessed at baseline and at 6, 12 and 24 weeks post-baseline. The primary outcome was ulcer status at 24 weeks, i.e. healed vs not healed. RESULTS: After controlling for clinical and demographic determinants of healing, ulcer healing at 24 weeks was predicted by confrontation coping, but not by depression or anxiety. Patients with unhealed ulcers exhibited greater confrontation coping (model including depression: OR 0.809, 95% CI 0.704-0.929, p = 0.003; model including anxiety: OR 0.810, 95% CI 0.704-0.930, p = 0.003). However, change in ulcer size over the observation period was associated with depression only (p = 0.04, d = 0.31). Healed ulcers by 24 weeks were also associated with lower evening cortisol, higher precursor MMP2 and a greater cortisol awakening response. CONCLUSIONS/INTERPRETATION: Confrontation coping and depression predict ulcer healing. Our preliminary enquiry into biological mechanisms suggests that cortisol and precursor MMP2 may underlie these relationships.

Explaining all without causing unnecessary harm: Is there scope for positively framing medical risk information?

Clinicians in the United Kingdom are now legally obliged to tell patients about every risk involved in prescribed medical treatments. Although important for informed consent, warning patients of risks such as side-effects can increase the incidence of these very side-effects, through the nocebo effect. Positively framing risk information could be a potential solution to this dilemma, and preliminary data has shown it is effective in healthy volunteers receiving a sham drug. Future research is needed to test its effectiveness in a clinical population.

A cross-sectional comparison study of cognitive and emotional well-being in oral cancer patients.

The main aim of this study was to establish whether oral cancer patients were at risk of long-term problems with adaptation, whilst investigating contributory factors using a framework of Subjective Well-Being. Three samples of patients treated for either oral cancer (n=115); throat cancer (n=47), or benign conditions of the salivary gland (n=33) were recruited into a cross-sectional, postal questionnaire study. A gender and age matched healthy normative sample (n=115) was recruited for comparison purposes. Measures included The Satisfaction with Life Scale, the General Health Survey (SF-12), Life Orientation Test and the Hospital Anxiety and Depression Scale. Patients with oral cancer demonstrated similar levels of cognitive and emotional well-being as the other samples. Time since treatment and the majority of clinical and treatment related factors had no effect on cognitive and emotional adaptation in any of the patient samples.

The relationship between the Patient Generated Index (PGI) and measures of HR-QoL following diagnosis with head and neck cancer: are illness and treatment perceptions determinants of judgment-based outcomes?

OBJECTIVES: The primary objectives of this study were to examine the relationship between factors specified in the extended Self-Regulation Model (SRM) (illness and treatment perceptions and coping strategy) and three types of QoL outcome. Secondary objectives were to examine the relationships between outcome measures (general and cancer-specific HR-QoL and the Patient Generated Index (PGI)). DESIGN: Cross-sectional questionnaire study. METHODS: Eighty-two newly diagnosed patients with head and neck cancer (HNC) completed the Illness Perception Questionnaire--Revised (IPQ-R), the Beliefs about Medicines Questionnaire (BMQ), the Hospital Anxiety and Depression Scale (HADS), the Brief COPE and the Life Orientation Test (LOT-R). Patient outcomes were assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, MOS Short Form Health Survey (SF-12v2) and the Patient Generated Index (PGI). RESULTS: These pre-treatment cross-sectional results have shown that key components of the SRM (beliefs and coping) were explanatory factors of HR-QoL outcomes. The PGI was not associated with any of the components of the SRM. The PGI was partially correlated with HR-QoL measures; in particular, Global QoL/health status (EORTC) and Mental Component Summary scores (SF-12). CONCLUSIONS: Our findings suggest that the illness perceptions approach may be a useful method for eliciting and understanding patients' beliefs regarding HNC. In order to maximize outcomes, simple interventions could address particular patient beliefs and coping styles.

How satisfied are head and neck cancer (HNC) patients with the information they receive pre-treatment? Results from the satisfaction with cancer information profile (SCIP).

Recent UK government recommendations state that high quality information must be provided for cancer patients. The objectives of this study were firstly, to explore how satisfied head and neck cancer (HNC) patients were with information provided about their illness and treatment, in order to identify areas of improvement. Secondly, to assess the extent to which satisfaction with information before treatment was predictive of long-term outcomes. Patients completed the satisfaction with information profile (SCIP), the Hospital Anxiety and Depression Scale (HADS) and the SF-12 Health Survey (SF-12v2) before treatment (n=82), 1 month after the end of treatment (n=68) and 6-8 months later (n=50). Patients were generally satisfied with information, however key areas of improvement were identified, such as the provision of information about support groups, where to go for financial advice and the long-term affects of treatment on ability to work, physical functioning and QoL. Satisfaction with information before treatment was predictive of depression and Mental Component Summary scores (HR-QoL) 6-8 months after the end of treatment. This study highlights the need for tailored information provision and the impact on longitudinal outcomes of satisfying patient's needs for information prior to treatment.

Head and neck cancer: to what extent can psychological factors explain differences between health-related quality of life and individual quality of life?

AIMS: To assess the extent to which individualised quality of life (QoL) was related to standardised health-related quality of life (HR-QoL), and to assess how much of the variation in each of these measures could be explained by psychological variables. METHODS: Fifty-five patients with newly diagnosed head and neck cancer completed the following outcome measures: the Patient Generated Index (PGI), the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the Short Form 12 version 2 (SF-12v2). Explanatory factors were measured with the following: the Illness Perceptions Questionnaire-Revised (IPQ-R), the Beliefs about Medicines Questionnaire (BMQ), the Hospital Anxiety and Depression Scale (HADS), and the Brief COPE (a shortened version of the COPE). MAIN FINDINGS: Standardised and individualised QoL measures were correlated only partly. The PGI correlated only with EORTC QLQ-C30 domains of emotional and cognitive functioning and SF-12 domains of mental health, emotional role, social, and physical role. The underlying psychological factors explaining each of the three outcome measures were different. CONCLUSIONS: Respondent-generated measures such as the PGI could be used as an adjunct to more standardised measures of HR-QoL clinically. This has implications for assessing the impact of head and neck cancer on individualised QoL and also for improving patients' outcome through interventions aimed at targeting underlying psychological factors.

Immunocytochemical and biochemical evidence for the presence of calmodulin in bull sperm flagellum. Isolation and characterization of sperm calmodulin.

Upon fluorescent staining with a goat antibody anti-ram testis calmodulin, washed bull sperm appears to contain calmodulin in the acrosome, in the post acrosomal region, in the neck region probably associated with the implantation plates and thin laminated fibers, and in a sheath around the upper part of the flagellum. Heads and midpieces + tails were separated by elutriation of sonicated sperm. Immunofluorescent labeling of fragments confirms the presence of calmodulin in implantation plates, where sonication disrupted heads from midpieces, and in a sheath around the midpiece and the upper part of the principal piece. These results were confirmed by electrophoretic and radioenzymatic assays of calmodulin in the fragments, using calmodulin-deficient Ca2+/calmodulin-dependent myosin light chain kinase. Small but significant amounts (approx. 3 micrograms per 10 (10) sperm) are found in midpieces + tails vs. approx. 280 micrograms in the same number of heads. These results are in agreement with a recent report from Jones et al. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 2772-2776. Sperm calmodulin was purified from a whole sperm 1 M KCl extract and found to exhibit the same characteristics as other mammalian calmodulins isolated so far in terms of ultraviolet absorption spectrum and amino acid composition, including one residue of epsilon-N-trimethyllysine. Its behavior upon SDS-polyacrylamide gel electrophoresis was dependent on the presence or absence of Ca2+. The high performance liquid chromatography tryptic peptide maps were similar, if not identical, to mammalian calmodulin maps (Autric et al. (1980) Biochim. Biophys. Acta 631, 139-147). Sperm calmodulin is therefore probably identical to the somatic cell protein.

Are psycho-social and behavioural factors related to health related-quality of life in patients with head and neck cancer? A systematic review.

The survival rate in advanced cancer of the head and neck has remained at approximately 50%, and efforts are now directed towards reducing the impact of the disease and its treatment in terms of functioning and health related-quality of life (HR-QoL). Factors such as stage, site of disease and type of treatment all impact on HR-QoL, but it is unclear what additional factors influence HR-QoL. A systematic review was undertaken of studies that have investigated psycho-social or behavioural factors associated with HR-QoL in this patient group. Literature was systematically searched using electronic databases and hand-searching relevant journals. Data were sought on HR-QoL and studies were only included if the measurement instrument was recognised as a reliable and valid measure of HR-QoL. Studies had to include at least one psycho-social or behavioural predictor variable. Sixteen studies fulfilling the inclusion criteria were identified and reviewed. Five main factors were associated with varying degrees with HR-QoL, personality, social support, satisfaction with consultation and information, behavioural factors, such as consuming alcohol and smoking, and depressive symptoms. The major difficulty with synthesising the findings was the amount of different indices of QoL that have been used. However, a number of psycho-social factors have been investigated in relation to HR-QoL in head and neck cancer patients, some of which are potentially modifiable, such as those related to informational needs. Further research is needed to investigate other psychological factors which may influence aspects of HR-QoL. By understanding the relationship between HR-QoL and potentially modifiable variables, interventions can be designed with the aim of improving a patient's long-term well-being.

Rhizobia can induce nodules in white clover by "hijacking" mature cortical cells activated during lateral root development.

We examined a range of responses of root cortical cells to Rhizobium sp. inoculation to investigate why rhizobia preferentially nodulate legume roots in the zone of emerging root hairs, but generally fail to nodulate the mature root. We tested whether the inability to form nodules in the mature root is due to a lack of plant flavonoids to induce the bacterial genes required for nodulation or a failure of mature cortical cells to respond to Rhizobium spp. When rhizobia were inoculated in the zone of emerging root hairs, changes in beta-glucuronidase (GUS) expression from an auxin-responsive promoter (GH3), expression from three chalcone synthase promoters, and the accumulation of specific flavonoid compounds occurred in cortical cells prior to nodule formation. Rhizobia failed to induce these responses when inoculated in the mature root, even when co-inoculated with nod gene-inducing flavonoids. However, mature root hairs remained responsive to rhizobia and could support infection thread formation. This suggests that a deficiency in signal transduction is the reason for nodulation failure in the mature root. However, nodules could be initiated in the mature root at sites of lateral root emergence. A comparison between lateral root and nodule formation showed that similar patterns of GH3:gusA expression, chalcone synthase gene expression, and accumulation of a particular flavonoid compound occurred in the cortical cells involved in both processes. The results suggest that rhizobia can "hijack" cortical cells next to lateral root emergence sites because some of the early responses required for nodule formation have already been activated by the plant in those cells.