Current management of adults receiving oral anti-cancer medications: A scoping review.

PURPOSE: Oral anti-cancer medication (OAM) has revolutionised oncology care. Due to their potential toxicities and associated safety challenges ongoing assessment and monitoring is essential; currently generally performed in acute care settings. Internationally there exists a transformative vision to shift patient care from acute to primary care. A nurse-led integrated model of care could be developed for OAM patient management in primary care. The aim of this study was to examine international literature regarding current clinical management practices for assessment and monitoring of patients receiving OAM. METHODS: Following PRISMA-ScR guidelines, databases MEDLINE, CINAHL and Web of Science were searched for English studies published between 2010 and 2020 using keywords: assessment, cancer, care, management, oral anticancer medications. Articles were screened and assessed for eligibility. From eligible studies, data were extracted to summarize, collate and make a narrative account of the findings. RESULTS: 2261 papers were reviewed, 14 met inclusion criteria. Three phases of management are reported: 1. Patient treatment plan development; 2. Patient education; 3. Patient monitoring. Within these phases seven specific stages of care were identified broadly representing the patient's journey: (1) treatment decision, (2) prescribing of OAM, (3) OAM dispensing and administration, (4) maximising patient safety (5) ongoing patient assessment (6) patient support (7) communication with other health-care professionals. CONCLUSIONS: Despite a paucity of international literature, a dedicated OAM clinic was endorsed as a means to achieve improved care. Nurses and pharmacists were identified as being of particular importance especially in education and ongoing management of patients receiving OAMs.

Cigarette smoking significantly alters sperm DNA methylation patterns.

Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre-conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never-smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome-wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome-wide in sperm DNA from men who smoke compared with never-smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre-conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.

Implementing international sexual counselling guidelines in hospital cardiac rehabilitation: development of the CHARMS intervention using the Behaviour Change Wheel.

BACKGROUND: Decreased sexual activity and sexual problems are common among people with cardiovascular disease, negatively impacting relationship satisfaction and quality of life. International guidelines recommend routine delivery of sexual counselling to cardiac patients. The Cardiac Health and Relationship Management and Sexuality (CHARMS) baseline study in Ireland found, similar to international findings, limited implementation of sexual counselling guidelines in practice. The aim of the current study was to develop the CHARMS multi-level intervention to increase delivery of sexual counselling by healthcare professionals. We describe the methods used to develop the CHARMS intervention following the three phases of the Behaviour Change Wheel approach: understand the behaviour, identify intervention options, and identify content and implementation options. Survey (n = 60) and focus group (n = 14) data from two previous studies exploring why sexual counselling is not currently being delivered were coded by two members of the research team to understand staff's capability, opportunity, and motivation to engage in the behaviour. All potentially relevant intervention functions to change behaviour were identified and the APEASE (affordability, practicability, effectiveness, acceptability, side effects and equity) criteria were used to select the most appropriate. The APEASE criteria were then used to choose between all behaviour change techniques (BCTs) potentially relevant to the identified functions, and these BCTs were translated into intervention content. The Template for Intervention Description and Replication (TIDieR) checklist was used to specify details of the intervention including the who, what, how and where of proposed intervention delivery. RESULTS: Providing sexual counselling group sessions by cardiac rehabilitation staff to patients during phase III cardiac rehabilitation was identified as the target behaviour. Education, enablement, modelling, persuasion and training were selected as appropriate intervention functions. Twelve BCTs, linked to intervention functions, were identified for inclusion and translated into CHARMS intervention content. CONCLUSIONS: This paper details the use of Behaviour Change Wheel approach to develop an implementation intervention in an under-researched area of healthcare provision. The systematic and transparent development of the CHARMS intervention will facilitate the evaluation of intervention effectiveness and future replication and contribute to the advancement of a cumulative science of implementation intervention design.

Genome-wide DNA methylation profiling in zebrafish.

Genomic DNA methylation functions to repress gene expression by interfering with transcription factor binding and/or recruiting repressive chromatin machinery. Recent data support contribution of regulated DNA methylation to embryonic pluripotency, development, and tissue differentiation; this important epigenetic mark is chemically stable yet enzymatically reversible-and heritable through the germline. Importantly, all the major components involved in dynamic DNA methylation are conserved in zebrafish, including the factors that "write, read, and erase" this mark. Therefore, the zebrafish has become an excellent model for studying most biological processes associated with DNA methylation in mammals. Here we briefly review the zebrafish model for studying DNA methylation and describe a series of methods for performing genome-wide DNA methylation analysis. We address and provide methods for methylated DNA immunoprecipitation followed by sequencing (MeDIP-Seq), bisulfite sequencing (BS-Seq), and reduced representation bisulfite sequencing (RRBS-Seq).

Measuring and recording outcome.

Achieving good health outcomes for patients is the fundamental purpose of healthcare. What really matters to patients is the outcome of an intervention and the effect it will have on their wellbeing and life expectancy. After media coverage, and public enquiry into high mortality rates for paediatric cardiac surgery at the Bristol Royal Infirmary during the early 1990s, mortality rates for paediatric cardiac surgical procedures decreased dramatically both in Bristol and nationally. There can be little doubt that one of the prime 'drivers for change' was the placement of outcome data into the public domain. After events in Bristol, the Society for Cardiothoracic Surgery in Britain and Ireland (SCTS) has taken the lead in measuring and publishing clinical outcome data. It has also discussed how outcome data could be used to assess an individual's clinical performance and how, in the future, this might be linked to continuing professional development, appraisal, and revalidation. Measuring quality and outcome in healthcare is complex. Ideal outcome measures should be specific, sensitive, reliable, responsive, validated, timely, and easy to measure. Monitoring of outcomes can be 'process' orientated or 'clinically' orientated. The 2010 National Health Service (NHS) White Paper aimed for an NHS which 'moves away from centrally driven process targets and focuses on delivering outcomes which matter to people'. Measuring outcome in anaesthesia is problematic. There are issues around clinical coding, risk adjustment, the influence of clinical teamworking, and environmental factors. The National Institute of Academic Anaesthesia (NIAA) has identified that the description of clinical practice in anaesthesia and perioperative medicine is currently limited by a lack of valid, reliable quality measures. The NIAA suggests that there is a requirement for further research into identifying the anaesthetic outcome indicators which are most relevant to patients, and then benchmarking the performance of anaesthetic departments and anaesthetists.

The relationship between clinical signs and dry eye symptoms.

PURPOSE: To evaluate (i) the relationship between traditional and new clinical tests (lid-wiper epitheliopathy (LWE), lid-parallel conjunctival folds (LIPCOF)) and dry eye symptoms in non-contact lens wearers, and (ii) that a combination of these tests can improve predictive ability for the development of dry eye symptoms. METHODS: Tear meniscus height (TMH), non-invasive break-up time (NIBUT), ocular hyperaemia, LIPCOF, phenol red thread test (PRTT), corneal and conjunctival staining, and LWE grades were observed in a cohort of 47 healthy, non-lens wearers (male=17, female=30, median age=35 years, range=19-70). Symptoms were assessed using the Ocular Surface Disease Index (OSDI). RESULTS: LWE was significantly correlated to both temporal and nasal LIPCOF (0.537 -0.248, P < 0.001). Significant correlations were found between NIBUT and TMH (r=0.461, P=0.001) and PRTT (r = 0.640, P < 0.001). OSDI scores were significant correlated to NIBUT, TMH, PRTT, LIPCOF, and LWE (r>∣0.31∣; P<0.05). Significant discriminators of OSDI+/- were NIBUT (area under the receiver operative characteristic curve (AUC)=0.895), TMH (0.715), PRTT (0.781), LIPCOF (temporal/nasal/Sum 0.748/0.828/0.816), and LWE (0.749). Best predictive ability was achieved by combining NIBUT with nasal LIPCOF (AUC=0.944). CONCLUSIONS: The individual tests NIBUT, TMH, PRTT, LIPCOF, and LWE were significantly, but moderately, related to OSDI scores. The strongest relationship appeared by combining NIBUT with nasal LIPCOF.

Changes in structural aspects of mood during 39-66 h of sleep loss using matched controls.

A number of studies have described mood change during sleep loss in the laboratory, however, an understanding of fluctuations in structural aspects of mood under such conditions is lacking. Sixty-two healthy young adults completed one of three possible conditions: one (n = 20) or two (n = 23) nights of sleep loss or the control condition which consisted of one (n = 9) or two (n = 10) nights of 9 h time in bed. The Mood Scale II was completed every two waking hours and data were analysed in terms of the frequency and intensity of mood reports. Overall, sleep loss conditions were associated with significantly less frequent happiness and activation and more frequent fatigue reports (p < 0.001). Intensity was also significantly reduced for activation and happiness, and increased for depression, anger and fatigue (p < 0.05). Interestingly, there were no significant differences in anger following two nights in the laboratory with or without sleep. Further, two nights in the lab with normal sleep was associated with significant increases in depression intensity (p < 0.05). Findings support the hypothesis of a mood regulatory function of sleep and highlight the relative independence of frequency and intensity and of positive and negative mood dimensions. Findings also suggest that the laboratory environment, in the absence of sleep loss, may have a significant negative impact on mood.

Tear film volume and protein analysis in full-term newborn infants.

PURPOSE: To investigate infant tear film secretion and protein profile, and to compare major tear proteins, such as immunoglobulin A, lactoferrin, and lysozyme, with those of adult controls. METHODS: Tears were collected, with a cellulose rod, from 40 healthy infants (19 female infants and 21 male infants, gestational duration: 39.71 ± 1.27 weeks) within 48 hours of birth and 22 adults (10 female infants and 12 male infants, mean age: 24.95 ± 3.63 years). A second collection was obtained from 14 of the infants (8 female infants and 6 male infants, postnatal age: 7.76 ± 6.14 weeks). The tear volume was measured, and protein in the samples was analyzed by Bradford assay and gel electrophoresis. RESULTS: Median tear volume (interquartile range) was 0.5 µL (0.6-2 µL) for newborn infants, 2.5 µL (1.4-7.75 µL) for these infants at an older age, and 6 µL (2.73-12.75 µL) in adults (P < 0.001, Kruskall-Wallis test). Immunoglobulin A concentration was significantly lower in newborns (P < 0.001, analysis of variance). Lipocalin was present in 36% of the newborn tear samples, whereas serum albumin was found in 86%. Mean protein concentration (µg/µL ± SD) was 10.95 ± 5.51 in the newborns, 12.93 ± 3.99 in the older infants, and 13.04 ± 3.46 in the adults (P > 0.5, analysis of variance). CONCLUSIONS: This is the first study reporting an investigation of unstimulated infant tears, using a noninvasive collection method. Tear protein content demonstrated that the infant tear film is different to that in adults.

Effects of prolonged use of azithromycin in patients with cystic fibrosis: a meta-analysis.

Azithromycin has been studied as potential therapeutic anti-inflammatory agent for cystic fibrosis (CF) patients. Azithromycin (AZM) has been used as an immunomodulating agent, based on few small studies. Considering the cost and potential side effects of long-term azithromycin therapy, it is important to identify the group of patients that would benefit the most. Weighted mean difference was used for pulmonary function tests, and risk ratios for all other variables. The random-effects model was applied for all reports. Combining four studies (N=368), azithromycin showed increase in FEV(1) (3.53%, 95% CI 0.00, 7.07, p=0.05; I(2)=38%) and FVC (4.24%, 95% CI 2.02, 6.45, p=0.0002; I(2)=0%). When trials were analyzed by baseline Pseudomonas sputum colonization, the heterogeneity decreased (I(2)=0%), FEV(1) significantly increased to 4.66% (95% CI 1.18, 8.15, p=0.009), and FVC increased to 4.64% (95% CI 2.11, 7.17, p=0.0003). The GI side effects were 72% higher with azithromycin use (RR 1.72, 95% CI 1.33, 2.21, p=0.00003), the main side effects being nausea (RR 2.04, 95% CI 1.19, 3.45, p=0.009), and diarrhea (RR 2.12, 95% CI 1.10, 4.08, p=0.02). Azithromycin improves lung function of CF patients, especially in the subgroup colonized with Pseudomonas. However, nausea and diarrhea are significantly more frequent with azythromycin.

How red is a white eye? Clinical grading of normal conjunctival hyperaemia.

PURPOSE: To quantify the level of normal bulbar conjunctival hyperaemia using the Cornea and Contact Lens Research Unit (CCLRU) grading scale, and to investigate inter-observer agreement. METHODS: Bulbar conjunctival hyperaemia was assessed by two trained observers, using the CCLRU grading scale (zero to four units) interpolated into 0.1 increments, on the right eye of 121 healthy, non-contact lens-wearing subjects (male=58, female=63, median age=28 years, range 16-77). The eye was observed using a slit-lamp bio-microscope (x 10 magnification) under diffuse, white illumination. The subject's position of gaze was directed to allow grading of four quadrants: superior, nasal, inferior, and temporal conjunctiva. Bulbar redness was defined as the average of those four grades of conjunctival hyperaemia. A further twenty subjects were recruited to assess inter-observer agreement (male=8, female=12, median age=23 years). RESULTS: The average bulbar redness was 1.93 (+/-0.32 SD) units. The nasal (2.3+/-0.4) and temporal (2.1+/-0.4) quadrants were significantly redder than the superior (1.6+/-0.4) and inferior (1.7+/-0.4) quadrants (P<0.0001). Males had redder eyes than females by 0.2 units. Inter-observer 95% limits of agreement for bulbar redness was 0.38 units. CONCLUSIONS: The average bulbar redness of 1.9 units was higher than expected, reflecting the design of the grading scale. A bulbar redness of greater than 2.6 units may be considered abnormal, and a change in bulbar redness of > or =0.4 units may be significant.

Incidence and severity of keratoconus in Asir province, Saudi Arabia.

AIM: To assess the incidence and associated signs and symptoms of patients with keratoconus in Asir Province, Saudi Arabia. METHODS: 125 new keratoconus patients (51 male, 74 female; mean age 18.5 (SD 3.8) years; range 8--28 years) were recruited from referrals to the department of ophthalmology, Asir Central Hospital, over a 1 year period. Age, visual acuity, and keratometry were recorded along with clinical signs and symptoms. RESULTS: The incidence of keratoconus in Asir Province is 20 cases per 100,000 population. Also, the disease severity is high, as indicated by an early mean age (17.7 (3.6) years) with advanced stage keratoconus. Visual acuity, with either spectacles or rigid contact lenses, was 6/12 or better in 98% of eyes measured. Just over half (56%) of patients had atopic ocular disease. 16% of patients had a positive family history of the disease and 16% had atopic dermatitis (eczema and/or vitiligo). CONCLUSION: The incidence and severity of keratoconus in Asir Province, Saudi Arabia, is high with an early onset and more rapid progress to the severe disease stage at a young age. This might reflect the influence of genetic and/or environmental factor(s) in the aetiology of keratoconus.

The diversity of Phaseolus-nodulating rhizobial populations is altered by liming of acid soils planted with Phaseolus vulgaris L. in Brazil.

PCR-mediated restriction fragment length polymorphism (RFLP) analysis of the 16S-23S rRNA internally transcribed spacer (ITS) region and the 16S rRNA gene indicated that the rhizobial populations isolated from common bean (Phaseolus vulgaris L.) nodules in the unlimed soil from a series of five lime rates applied 6 years previously to plots of an acidic oxisol had less diversity than those from plots with higher rates of liming. Isolates affiliated with Rhizobium tropici IIB and Rhizobium leguminosarum bv. phaseoli were predominant independent of lime application. An index of richness based on the number of ITS groups increased from 2.2 to 5.7 along the soil liming gradient, and the richness index based on "species" types determined by RFLP analysis of the 16S rRNA gene varied from 0.5 to 1.4. The Shannon index of diversity, based on the number of ITS groups, increased from 1.8 in unlimed soil to 2.8 in limed soil, and, based on RFLP analysis of the 16S rRNA gene, ranged from 0.9 to 1.4. In the limed soil, the subpopulation of R. tropici IIB pattern types contained the largest number of ITS groups. In contrast, there were more R. leguminosarum bv. phaseoli types in the unlimed soil with the lowest pH than in soils with the highest pH. The number of ITS ("strain") groups within R. leguminosarum bv. phaseoli did not change with increased abundance of rhizobia in the soil, while with R. tropici IIB, the number of strain groups increased significantly. Some cultural and biochemical characteristics of Phaseolus-nodulating isolates were significantly related to changes in soil properties caused by liming, largely due to changes in the predominance of the rhizobial species groups.

Hydroxyurea significantly enhances tumor growth delay in vivo with herpes simplex virus thymidine kinase/ganciclovir gene therapy.

We have previously demonstrated with several cell lines in vitro that hydroxyurea (HU) synergistically enhances ganciclovir (GCV)-mediated cytotoxicity in bystander cells. In this study, we evaluated the role of DNA synthesis inhibition on enhanced bystander killing and assessed whether addition of HU would improve the efficacy of the HSV-TK/GCV system in vivo. Compared with GCV treatment alone, addition of HU resulted in increased DNA synthesis inhibition and delayed progression through S phase following removal of drug. In a xenograft tumor model, 1:10 and 1:1 mixtures of HSVtk- and LacZ-expressing SW620 cells were injected s.c. in the flanks of nude mice and treated i.p. (100 mg/kg GCV, 1500 mg/kg HU) daily for 5 days. Tumors from mice treated with GCV alone grew rapidly and increased to 10 times their initial size in 15.7 +/- 1.8 and 16.0 +/- 0.9 days for 1:10 and 1:1 mixtures, respectively. However, when both GCV and HU were administered in combination, a single complete tumor regression was observed in both the 1:10 and 1:1 groups. In the remaining mice treated with GCV/HU, it took 23.2 +/- 2.1 (1:10) and 26.4 +/- 3.8 days (1:1) to obtain a similar 10-fold increase in tumor size.

Rapid skin anaesthesia using high velocity lignocaine particles: a prospective placebo controlled trial.

BACKGROUND: Local anaesthetic creams (EMLA and Ametop) are used widely to provide pain free intravenous cannulation. However, they take a minimum of 45 minutes to become effective. AIMS: To evaluate a prototype device, dermal Powderject lidocaine (DPL), that delivers high velocity lignocaine particles into the skin. METHODS: A total of 132 children (aged 4-12 years) were randomised to receive either a sham delivery or a delivery of DPL on the skin at the antecubital fossa, or back of hand. Pain of intravenous cannulation was assessed four minutes later using self reporting behaviours and blinded observation with standard pain assessment tools. The trial was designed to measure both efficacy of skin anaesthesia and potential skin damage with increasing driving pressure of the device (30 or 40 bar), and different lignocaine particle sizes (<38 micrometer or 38-53 micrometer) in a block randomised fashion. RESULTS: A total of 128 patients were evaluable. There was a trend towards improved anaesthesia at higher device pressures at the antecubital fossa with both self reporting and blinded observation. Acceptable analgesia was achieved in 90% of patients for high pressure at both particle sizes compared to 60% and 40% for the sham device using self reporting measures. The observed differences using the blinded observer were similar: 90% v 20% (40 bar and small particles v sham), and 80% v 40% (40 bar and large particles v sham). At the back of hand the differences between active and sham devices were not significant. The device was well tolerated and not associated with pain on deployment. One patient had mild petechiae and oedema after deployment (Draize score of 3). CONCLUSIONS: This prototype device appears to provide significant skin anaesthesia at the antecubital fossa, but not at the back of hand. The device is not painful to use and causes only minor short term skin changes.

On the photoreactivity of 4,5-dithiophen-3-yl-[1,3]dithiol-2-one. The first preparation of a thieno[3,4-c]dithiine.

[reaction: see text]. Irradiation of 4,5-dithiophen-3-yl-[1,3]dithiol-2-one 1 at lambda > 330 nm gave the thieno[3,4-c]dithiine 2, the first example of this heterocyclic system

The minimum stimulus energy required to produce a cooling sensation in the human cornea.

PURPOSE: To estimate the minimum stimulus energy required to stimulate the corneal nerves, using a thermally cooling stimulus. METHODS: The localised temperature change produced in the pre-corneal tear film by the air-pulse stimulus of the Non-Contact Corneal Aesthesiometer (NCCA) was analysed using a thermal imaging camera. Assuming that the cornea behaves as a near perfect black-body, the threshold for energy loss was calculated by combining Stefan-Boltzmann's law and Kirchoff's law for imperfections in black-body radiation, taking into account the likely thermal conductivity of the human cornea. RESULTS: The average normal subject has a threshold for detecting a cooling effect when the local corneal tear film surface temperature drops from a mean of 33.2-32.9 degrees C (i.e. 0.3 degrees C), over a 1 mm diameter circular area (0.785 mm2), and a stimulus time duration of 0.9 s. This gives rise to a sensation threshold for perceiving a loss of heat energy of 7.0 ergs, or 7.0 x 10(-7) joules. CONCLUSION: The cornea possesses stimulus specific receptors, which have an exquisite sensitivity to a rapid, thermally cooling stimulus.

Stoichiometry, abundance, and functional significance of the hsp90/hsp70-based multiprotein chaperone machinery in reticulocyte lysate.

Rabbit reticulocyte lysate contains a multiprotein chaperone system that assembles the glucocorticoid receptor (GR) into a complex with hsp90 and converts the hormone binding domain of the receptor to its high affinity steroid binding state. This system has been resolved into five proteins, with hsp90 and hsp70 being essential and Hop, hsp40, and p23 acting as co-chaperones that optimize assembly. Hop binds independently to hsp70 and hsp90 to form an hsp90.Hop.hsp70 complex that acts as a machinery to open up the GR steroid binding site. Because purified hsp90 and hsp70 are sufficient for some activation of GR steroid binding activity, some investigators have rejected any role for Hop in GR.hsp90 heterocomplex assembly. Here, we counter that impression by showing that all of the Hop in reticulocyte lysate is present in an hsp90.Hop.hsp70 complex with a stoichiometry of 2:1:1. The complex accounts for approximately 30% of the hsp90 and approximately 9% of the hsp70 in lysate, and upon Sephacryl S-300 chromatography the GR.hsp90 assembly activity resides in the peak containing Hop-bound hsp90. Consistent with the notion that the two essential chaperones cooperate with each other to open up the steroid binding site, we also show that purified hsp90 and hsp70 interact directly with each other to form weak hsp90.hsp70 complexes with a stoichiometry of 2:1.

Enhancement of REM sleep during extraocular light exposure in humans.

This study examined the effects on sleep of light administered to an extraocular site. A 3-h photic stimulus was applied to the popliteal region during sleep in 14 human subjects. Each subject also underwent a control stimulus condition during a separate laboratory session. The proportion of rapid eye movement (REM) sleep during the 3-h light administration session increased by an average of 31% relative to the control condition. The frequency but not the duration of REM episodes was altered during light exposure, thereby shortening the REM/non-REM (NREM) cycle length. No other sleep stages were significantly affected during light administration nor was sleep architecture altered after the light-exposure interval. These results confirm that extraocular light is transduced into a signal that is received and processed by the human central nervous system. In addition, they expand to a novel sensory modality previous findings that REM sleep can be enhanced by sensory stimulation.