Fifteen-minute consultation: Fractures in non-ambulant children with cerebral palsy.

OBJECTIVE: To describe a safeguarding decision pathway for the assessment of osteopenic fractures in non-ambulant children with cerebral palsy. METHOD: Literature review and consensus practice of a child safeguarding team, including clinicians and social workers. CONCLUSION: Low-energy fractures of the lower limb in non-ambulant children with cerebral palsy are relatively common and explained by the presence of reduced bone strength, in the absence of any other unexplained injuries or safeguarding concerns.

Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom.

The COVID-19 pandemic has resulted in unprecedented challenges for healthcare systems worldwide. It has also stimulated research in a wide range of areas including rapid diagnostics, novel therapeutics, use of technology to track patients and vaccine development. Here, we describe our experience of rapidly setting up and delivering a novel COVID-19 vaccine trial, using clinical and research staff and facilities in three National Health Service Trusts in Cambridgeshire, United Kingdom. We encountered and overcame a number of challenges including differences in organisational structures, research facilities available, staff experience and skills, information technology and communications infrastructure, and research training and assessment procedures. We overcame these by setting up a project team that included key members from all three organisations that met at least daily by teleconference. This group together worked to identify the best practices and procedures and to harmonise and cascade these to the wider trial team. This enabled us to set up the trial within 25 days and to recruit and vaccinate the participants within a further 23 days. The lessons learned from our experiences could be used to inform the conduct of clinical trials during a future infectious disease pandemic or public health emergency.

Symptoms and patient factors associated with longer time to diagnosis for colorectal cancer: results from a prospective cohort study.

BACKGROUND: The objective of this study is to investigate symptoms, clinical factors and socio-demographic factors associated with colorectal cancer (CRC) diagnosis and time to diagnosis. METHODS: Prospective cohort study of participants referred for suspicion of CRC in two English regions. Data were collected using a patient questionnaire, primary care and hospital records. Descriptive and regression analyses examined associations between symptoms and patient factors with total diagnostic interval (TDI), patient interval (PI), health system interval (HSI) and stage. RESULTS: A total of 2677 (22%) participants responded; after exclusions, 2507 remained. Participants were diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer (91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple first symptoms were common. In this referred population, rectal bleeding was the only initial symptom more frequent among cancer than non-cancer cases (34.2% vs 23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days, P=0.142). First symptoms associated with shorter TDIs were rectal bleeding, change in bowel habit, 'feeling different' and fatigue/tiredness. Anxiety, depression and gastro-intestinal co-morbidities were associated with longer HSIs and TDIs. Symptom duration-dependent effects were found for rectal bleeding and change in bowel habit. CONCLUSIONS: Doctors and patients respond less promptly to some symptoms of CRC than others. Healthcare professionals should be vigilant to the possibility of CRC in patients with relevant symptoms and mental health or gastro-intestinal comorbidities.

Modification of T cell responses by stem cell mobilization requires direct signaling of the T cell by G-CSF and IL-10.

The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects on a broad range of cells and IL-10 is a key regulator of many of these effects. Using mixed radiation chimeras in which the hematopoietic or nonhematopoietic compartments were wild-type, IL-10(-/-), G-CSFR(-/-), or combinations thereof we demonstrated that the attenuation of alloreactive T cell responses after G-CSF mobilization required direct signaling of the T cell by both G-CSF and IL-10. IL-10 was generated principally by radio-resistant tissue, and was not required to be produced by T cells. G-CSF mobilization significantly modulated the transcription profile of CD4(+)CD25(+) regulatory T cells, promoted their expansion in the donor and recipient and their depletion significantly increased graft-versus-host disease (GVHD). In contrast, stem cell mobilization with the CXCR4 antagonist AMD3100 did not alter the donor T cell's ability to induce acute GVHD. These studies provide an explanation for the effects of G-CSF on T cell function and demonstrate that IL-10 is required to license regulatory function but T cell production of IL-10 is not itself required for the attenuation GVHD. Although administration of CXCR4 antagonists is an efficient means of stem cell mobilization, this fails to evoke the immunomodulatory effects seen during G-CSF mobilization. These data provide a compelling rationale for considering the immunological benefits of G-CSF in selecting mobilization protocols for allogeneic stem cell transplantation.

Testing methods to estimate population size for wastewater treatment plants using census data: Implications for wastewater-based epidemiology.

In wastewater-based epidemiology (WBE), wastewater loads are commonly reported as a per capita value. Census population counts are often used to obtain a population size to normalise wastewater loads. However, the methods used to calculate the population size of wastewater treatment plants (WWTPs) from census data are rarely reported in the WBE literature. This is problematic because the geographical extents of wastewater catchments and census area units rarely align perfectly with each other and exist at different spatial scales. This complicates efforts to estimate the number of people serviced by WWTPs in these census area units. This study compared four geospatial methods to combine wastewater catchment areas and census area units to calculate the census population size of wastewater treatment plants. These methods were applied nationally to WWTPs across New Zealand. Population estimates varied by up to 73 % between the methods, which could skew comparisons of per capita wastewater loads between sites. Variability in population estimates (relative standard deviation, RSD) was significantly higher in smaller catchments (rs = -0.727, P < .001), highlighting the importance of method selection in smaller sites. Census population estimates were broadly similar to those provided by wastewater operators, but significant variation was observed for some sites (ranging from 42 % lower to 78 % higher, RSD = 262 %). We present a widely applicable method to calculate population size from census, which involves disaggregating census area units by individual properties. The results reinforce the need for transparent reporting to maintain confidence in the comparison of WBE across sites and studies.

Jointly estimating epidemiological dynamics of Covid-19 from case and wastewater data in Aotearoa New Zealand.

BACKGROUND: Timely and informed public health responses to infectious diseases such as COVID-19 necessitate reliable information about infection dynamics. The case ascertainment rate (CAR), the proportion of infections that are reported as cases, is typically much less than one and varies with testing practices and behaviours, making reported cases unreliable as the sole source of data. The concentration of viral RNA in wastewater samples provides an alternate measure of infection prevalence that is not affected by clinical testing, healthcare-seeking behaviour or access to care. METHODS: We construct a state-space model with observed data of levels of SARS-CoV-2 in wastewater and reported case incidence and estimate the hidden states of the effective reproduction number, R, and CAR using sequential Monte Carlo methods. RESULTS: We analyse data from 1 January 2022 to 31 March 2023 from Aotearoa New Zealand. Our model estimates that R peaks at 2.76 (95% CrI 2.20, 3.83) around 18 February 2022 and the CAR peaks around 12 March 2022. We calculate that New Zealand's second Omicron wave in July 2022 is similar in size to the first, despite fewer reported cases. We estimate that the CAR in the BA.5 Omicron wave in July 2022 is approximately 50% lower than in the BA.1/BA.2 Omicron wave in March 2022. CONCLUSIONS: Estimating R, CAR, and cumulative number of infections provides useful information for planning public health responses and understanding the state of immunity in the population. This model is a useful disease surveillance tool, improving situational awareness of infectious disease dynamics in real-time.

To make informed public health decisions about infectious diseases, it is important to understand the number of infections in the community. Reported cases, however, underestimate the number of infections and the degree of underestimation likely changes with time. Wastewater data provides an alternative data source that does not depend on testing practices. Here, we combined wastewater observations of SARS-CoV-2 with reported cases to estimate the reproduction number (how quickly infections are increasing or decreasing) and the case ascertainment rate (the fraction of infections reported as cases). We apply the model to Aotearoa New Zealand and demonstrate that the second wave of infections in July 2022 had approximately the same number of infections as the first wave in March 2022 despite reported cases being 50% lower.

The diagnosis and management of systemic autoimmune rheumatic disease-related interstitial lung disease: British Society for Rheumatology guideline scope.

Interstitial lung disease (ILD) is a significant complication of many systemic autoimmune rheumatic diseases (SARDs), although the clinical presentation, severity and outlook may vary widely between individuals. Despite the prevalence, there are no specific guidelines addressing the issue of screening, diagnosis and management of ILD across this diverse group. Guidelines from the ACR and EULAR are expected, but there is a need for UK-specific guidelines that consider the framework of the UK National Health Service, local licensing and funding strategies. This article outlines the intended scope for the British Society for Rheumatology guideline on the diagnosis and management of SARD-ILD developed by the guideline working group. It specifically identifies the SARDs for consideration, alongside the overarching principles for which systematic review will be conducted. Expert consensus will be produced based on the most up-to-date available evidence for inclusion within the final guideline. Key issues to be addressed include recommendations for screening of ILD, identifying the methodology and frequency of monitoring and pharmacological and non-pharmacological management. The guideline will be developed according to methods and processes outlined in Creating Clinical Guidelines: British Society for Rheumatology Protocol version 5.1.

The cost-effectiveness of a novel SIAscopic diagnostic aid for the management of pigmented skin lesions in primary care: a decision-analytic model.

OBJECTIVES: Pigmented skin lesions are commonly presented in primary care. Appropriate diagnosis and management is challenging because the vast majority are benign. The MoleMate system is a handheld SIAscopy scanner integrated with a primary care diagnostic algorithm aimed at improving the management of pigmented skin lesions in primary care. METHODS: This decision-model-based economic evaluation draws on the results of a randomized controlled trial of the MoleMate system versus best practice (ISRCTN79932379) to estimate the expected long-term cost and health gain of diagnosis with the MoleMate system versus best practice in an English primary care setting. The model combines trial results with data from the wider literature to inform long-term prognosis, health state utilities, and cost. RESULTS: Results are reported as mean and incremental cost and quality-adjusted life-years (QALYs) gained, incremental cost-effectiveness ratio with probabilistic sensitivity analysis, and value of information analysis. Over a lifetime horizon, the MoleMate system is expected to cost an extra £18 over best practice alone, and yield an extra 0.01 QALYs per patient examined. The incremental cost-effectiveness ratio is £1,896 per QALY gained, with a 66.1% probability of being below £30,000 per QALY gained. The expected value of perfect information is £43.1 million. CONCLUSIONS: Given typical thresholds in the United Kingdom (£20,000-£30,000 per QALY), the MoleMate system may be cost-effective compared with best practice diagnosis alone in a primary care setting. However, there is considerable decision uncertainty, driven particularly by the sensitivity and specificity of MoleMate versus best practice, and the risk of disease progression in undiagnosed melanoma; future research should focus on reducing uncertainty in these parameters.

Ultraviolet-C irradiation in the management of pressure ulcers in people with spinal cord injury: a randomized, placebo-controlled trial.

OBJECTIVE: To compare the effects of ultraviolet-C (UVC) with placebo-UVC on pressure ulcer healing in individuals with spinal cord injury (SCI). DESIGN: Double-blind randomized trial with stratification for ulcer location to buttock or lower extremity. Subjects were followed up for 1 year postintervention. SETTING: Rehabilitation institution. PARTICIPANTS: Adult inpatients and outpatients (N=43) with SCI and stage 2 to 4 pressure ulcers (n=58). INTERVENTIONS: Ulcers and periwound skin were irradiated 3 times per week using UVC or placebo-UVC. The endpoint was wound closure or hospital discharge without closure. MAIN OUTCOME MEASURES: Primary outcome was weekly percent area relative to baseline. Secondary outcomes were mean percent area change between consecutive weeks, surface appearance, weeks to closure, and impact on quality of life and wound status postintervention. RESULTS: Groups were similar at baseline for all demographic characteristics except ulcer duration (P=.02). Groups were similar when healing was compared overall. Subgroup analysis showed that the percent area relative to baseline for stage 2 buttock ulcers was significantly smaller in the group receiving UVC compared with placebo at weeks 3, 5, and 7. During weeks 1 through 8, these ulcers were 26% to 76% of baseline area using UVC versus 111% to 180% for placebo (achieved significant level [ASL], .03-.08; effect size, 0.5-0.8). Groups were similar in the percent area relative to baseline for stage 2 lower extremity ulcers. Group mean percent area change between consecutive weeks for all stage 2 ulcers was 36.6% with the use of UVC and 5.8% for placebo (ASL=.09). There were no group differences in the percent area relative to baseline and the mean percent area change between consecutive weeks for stage 3 to 4 ulcers. Groups were similar for all other secondary outcomes. CONCLUSIONS: UVC is beneficial for stage 2 buttock ulcers. Further studies are warranted using a larger sample size, carefully considered exclusion criteria, and strategies to ensure homogeneity of the groups that are being compared.

Nasal Septal Flaps for Repair of Large or Recurrent Palatal Fistula: Report of Technique and 4-Year Experience.

SUMMARY: Large or multiply recurrent oronasal fistulas following cleft palate repair present a challenging problem. Nasal septal mucoperichondrial flaps have been widely used for repair of skull base defects; however, their use in the repair of oronasal cleft palate fistulas has not previously been described. In this pilot study, the authors describe anterior palatal fistula repair using a nasal septal flap and review their experience with this technique over 4 years. Fourteen patients with anterior palatal fistulas not amenable to repair using local palatal flaps were included for analysis. The mean size of the fistula was 12 mm in maximum dimension. Flap healing with complete or near-complete closure of fistula was achieved in 13 patients (93%). Five of these patients had a small, slit-like residual fistula that was asymptomatic. Nasal septal flaps are a new technique for repair of large or recurrent palatal fistulas. The procedure is well-tolerated with minimal side effects, high success rate, and low incidence of recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

The B4 school check behaviour measures: findings from the Hawke's Bay evaluation.

The Before (B4) School Check is a free health and development check delivered by specifically trained nurses to four year old children throughout New Zealand, aimed to identify and address any health, behavioural, social or developmental concerns that could affect a child's ability to get the most benefit from school. Reported here are the results of an evaluation of the B4 School Checks in Hawke's Bay, focusing specifically on children assessed at the 84 School Check with behaviour issues as determined by the Strengths and Difficulties Questionnaire (SDQ). Health Hawke's Bay (HHB) records were reviewed to understand the number and demographics of the children assessed with behaviour issues at the B4 School Checks up to 31 August 2011, and the interventions to which they were referred. Telephone Interviews were conducted with 36 parents/caregivers of these children to address the questions, what difference did the B4 School Check make to children assessed with behaviour issues and what aspects of the B4 School Check delivery contributed to successful outcomes for these children? Results showed that child behaviour issues in Hawke's Bay were identified in more boys than girls and concentrated in more deprived families. Maori children were represented in numbers disproportional to the regional population. The majority of referrals for child behaviour directed parents/caregivers to non-governmental organisations for family support and parenting programmes. Thematic analysis was applied to the qualitative data derived from the interviews with parents/caregivers and results indicated high levels of satisfaction with the B4 School Check for behaviour and the referred outcomes. Implications for nursing practice arise from these findings in that they identify factors which contribute to what does and does not work well for achieving successful outcomes from the B4 School Check for behaviour.

Telephone Triage Toolkit for Children's cancer services: A quality initiative.

PURPOSE: Service development to improve patient safety and experience, and improve staff safety and confidence when managing telephone calls from parents or carers of children with cancer in the UK. METHOD: A multi-layered mixed methods approach broadly based on sequential PDSA (plan, do, study, act) cycles, to a series of quality initiative projects spanning 14 years. Various project styles and methods are described. RESULTS: A Telephone Triage Toolkit for children's cancer services was piloted, reviewed and rolled out across the UK. Similarities were identified between adult and paediatric cancer services when identifying the case for need, enabling partnership working. A scheduled review completed in 2020 included new developments in cancer treatment, building on user experience, local audits and national feedback, leading to a 2nd edition being implemented. CONCLUSIONS: Ground up, quality initiatives and collaborative working across organisations can be complex but draws on a wider pool of expertise and can lead to improved parent and staff experience of services. This initiative has improved practice and has application outside the UK.

Invariant natural killer T cell-natural killer cell interactions dictate transplantation outcome after alpha-galactosylceramide administration.

Invariant natural killer T cells (iNKT cells) have pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects. iNKT cells are activated through their T-cell receptors by glycolipid moieties (typically the alpha-galactosylceramide [alpha-GalCer] derivative KRN7000) presented within CD1d. We investigated the ability of modified alpha-GalCer molecules to differentially modulate alloreactivity and GVL. KRN7000 and the N-acyl variant, C20:2, were administered in multiple well-established murine models of allogeneic stem cell transplantation. The highly potent and specific activation of all type I NKT cells with C20:2 failed to exacerbate and in most settings inhibited GVHD late after transplantation, whereas effects on GVL were variable. In contrast, the administration of KRN7000 induced hyperacute GVHD and early mortality in all models tested. Administration of KRN7000, but not C20:2, was found to result in downstream interleukin (IL)-12 and dendritic cell (DC)-dependent natural killer (NK)- and conventional T-cell activation. Specific depletion of host DCs, IL-12, or donor NK cells prevented this pathogenic response and the induction of hyperacute GVHD. These data demonstrate the ability of profound iNKT activation to modulate both the innate and adaptive immune response via the DC-NK-cell interaction and raise concern for the use of alpha-GalCer therapeutically to modulate GVHD and GVL effects.

Protocol for the MoleMate UK Trial: a randomised controlled trial of the MoleMate system in the management of pigmented skin lesions in primary care [ISRCTN 79932379].

BACKGROUND: Suspicious pigmented lesions are a common presenting problem in general practice consultations; while the majority are benign a small minority are melanomas. Differentiating melanomas from other pigmented lesions in primary care is challenging: currently, 95% of all lesions referred to a UK specialist are benign. The MoleMate system is a new diagnostic aid, incorporating a hand-held SIAscopy scanner with a primary care diagnostic algorithm. This trial tests the hypothesis that adding the MoleMate system to current best primary care practice will increase the proportion of appropriate referrals of suspicious pigmented lesions to secondary care compared with current best practice alone. METHODS/DESIGN: The MoleMate UK Trial is a primary care based multi-centre randomised controlled trial, with randomisation at patient level using a validated block randomisation method for two age groups (45 years and under; 46 years and over). We aim to recruit adult patients seen in general practice with a pigmented skin lesion that cannot immediately be diagnosed as benign and the patient reassured. The trial has a 'two parallel groups' design, comparing 'best practice' with 'best practice' plus the MoleMate system in the intervention group. The primary outcome is the positive predictive value (PPV) of referral defined as the proportion of referred lesions seen by secondary care experts that are considered 'clinically significant' (i.e. biopsied or monitored). Secondary outcomes include: the sensitivity, specificity and negative predictive value (NPV) of the decision not to refer; clinical outcomes (melanoma thickness, 5 year melanoma incidence and mortality); clinician outcomes (Index of Suspicion, confidence, learning effects); patient outcomes (satisfaction, general and cancer-specific worry), and cost-utility. DISCUSSION: The MoleMate UK Trial tests a new technology designed to improve the management of suspicious pigmented lesions in primary care. If effective, the MoleMate system could reduce the burden on skin cancer clinics of patients with benign pigmented skin lesions, and improve patient care in general practice.

Evaluation of the MoleMate training program for assessment of suspicious pigmented lesions in primary care.

BACKGROUND: Pigmented skin lesions or 'moles' are a common presenting problem in general practice consultations: while the majority are benign, a minority are malignant melanomas. The MoleMate system is a novel diagnostic tool which incorporates spectrophotometric intracutaneous analysis (SIAscopy) within a non-invasive scanning technique and utilises a diagnostic algorithm specifically developed for use in primary care. The MoleMate training program is a short, computer-based course developed to train primary care practitioners to operate the MoleMate diagnostic tool. OBJECTIVES: This pre-trial study used mixed methods to assess the effectiveness and acceptability of a computer-based training program CD-ROM, developed to teach primary care practitioners to identify the seven features of suspicious pigmented lesions (SPLs) seen with the MoleMate system. METHOD: Twenty-five practitioners worked through the MoleMate training program: data on feature recognition and time taken to conduct the assessment of each lesion were collected. Acceptability of the training program and the MoleMate system in general was assessed by questionnaire. RESULTS: The MoleMate training program improved users' feature recognition by 10% (pre-test median 73.8%, p<0.001), and reduced the time taken to complete assessment of 30 SPLs (pre-test median 21 minutes 53 seconds, median improvement 3 minutes 17 seconds, p<0.001). All practitioners' feature recognition improved (21/21), with most also improving their time (18/21). Practitioners rated the training program as effective and easy to use. CONCLUSION: The MoleMate training program is a potentially effective and acceptable informatics tool to teach practitioners to recognise the features of SPLs identified by the MoleMate system. It will be used as part of the intervention in a randomised controlled trial to compare the diagnostic accuracy and appropriate referral rates of practitioners using the MoleMate system with best practice in primary care.

Contemporary challenges for specialist nursing in interstitial lung disease.

The role of clinical nurse specialists (CNSs) in interstitial lung disease (ILD) is evolving in response to clinical guidelines and the growth of clinical research. The role is well established in the UK, although more ILD posts are needed to ensure supply meets clinical demand. This phenomenon is also happening across Europe. An appreciation of the similarities and differences between CNS and advanced nurse practitioners is important given the challenges in defining, developing and supporting this nursing specialisation. Globally, different models exist. In some countries charitable organisations take a leading role in supporting patients. Many European centres look to the National Institute for Health and Care Excellence guidelines and quality standards as a template to develop and evaluate the role of the ILD CNS. We present a UK perspective in the context of a government subsidised healthcare system to promote professional discussion and debate regarding the future of nursing practice in the ILD specialty. KEY POINTS: ILDs are often complex and associated with significant mortality, morbidity and co-morbid conditions that require a technical healthcare skill setThere is worldwide shortage of nurses, low retention rates and retirement of many skilled nursesCollaboration across the ILD interdisciplinary community is needed to safeguard the future of our professions and high-quality patient careThe ILD interdisciplinary and nurse network has identified key priorities to help secure the future of the ILD clinical and academic nurse specialism. EDUCATIONAL AIMS: To explain the similarities and differences between clinical nurse specialists (CNSs) and advanced nurse practitioners (ANPs) in the context of ILD specialismTo review contemporary nursing specialism in the UK's government subsidised healthcare systemTo stimulate discussion and debate across the European/international respiratory community regarding the clinical and academic development of the ILD CNSTo identify key priorities that will support collaboration across the ILD interdisciplinary workforce in clinical practice and research.

Idiopathic pulmonary fibrosis: a holistic approach to disease management in the antifibrotic age.

Idiopathic pulmonary fibrosis (IPF) is the most common cause of interstitial lung disease (ILD) and carries a worse prognosis than many cancers. Until recently, there were no active treatment options available for patients with IPF, meaning palliation or lung transplantation in selected patients were the only options. The management of IPF has changed dramatically over the last decade with the advent of two antifibrotic agents; pirfenidone and nintedanib. These new agents have been shown to reduce decline in lung function and pirfenidone has been shown to reduce mortality. The changing landscape of IPF diagnosis and management present a number of issues that may be encountered including management of side effects related to antifibrotic therapy. This article aims to give an overview of the holistic approach to the management of patients with IPF, including antifibrotic management, symptom management and the invaluable role of the ILD specialist nurse.

Real World Experiences: Pirfenidone and Nintedanib are Effective and Well Tolerated Treatments for Idiopathic Pulmonary Fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) now has two licensed treatments available. Pirfenidone was the first drug to be licensed and approved for use, followed by nintedanib. We set out our real world experience with these agents in terms of their adverse events profile outside the restrictions of a clinical trial. We have demonstrated in the real world setting, that side effects are common and predominantly gastrointestinal with both therapies. Our study shows that the side effects can be effectively managed in the majority of patients with an acceptable discontinuation rate similar to that seen in the clinical trials. These findings are compelling despite the fact that the patients in our study are older, have severer disease as depicted by baseline lung function and more co-morbidities. Our data provides ongoing evidence of the safety and tolerability of both pirfenidone and nintedanib in patients who would not have met the rigorous criteria to be included in a clinical trial. Both these agents are effective in the management of IPF and slow the progression of this debilitating life limiting condition.

Persistence of DNA from laundered semen stains: Implications for child sex trafficking cases.

In sexual assault cases, particularly those involving internal child sex trafficking (ICST), victims often hide their semen-stained clothing. This can result in a lag time of several months before the items are laundered and subsequently seized during a criminal investigation. Although it has been demonstrated previously that DNA can be recovered from clothing washed immediately after semen deposition, laundered items of clothing are not routinely examined in ICST cases, due to the assumption that the time delay and washing would result in no detectable DNA. The aim of this study was to examine whether viable DNA profiles could be recovered from laundered semen stains where there has been a significant lag time between semen deposition from one or more individuals and one or more washes of the stained clothing. Items of UK school uniform (T-shirts, trousers, tights) were stained with fresh semen (either from a single donor or a 1:1 mixture from two donors) and stored in a wardrobe for eight months. Stained and unstained items (socks) were then washed at 30 °C or 60 °C and with non-biological or biological detergent. DNA samples extracted from the semen-stained sites and from the unstained socks were quantified and profiled. High quantities of DNA, (6-18 µg) matching the DNA profiles of the semen donors, were recovered from all semen-stained clothing that had been laundered once, irrespective of wash conditions. This quantity,and profile quality,did not decline significantly with multiple washes. The two donor semen samples yielded ∼ 10-fold more DNA from the T-shirts than from the trousers. This disparity resulted in the T-shirts yielding a ∼ 1:1 mixture of DNA from the two donors, whereas the trousers yielded a major DNA profile matching only that of the second donor. The quantities of DNA recovered from the unstained socks were an order of magnitude lower, with most of the DNA being attributable to the donor of the semen on the stained clothing within the same wash, demonstrating the transfer of semen-derived DNA among items of clothing in the washing machine. This study demonstrates that complete DNA profiles can be obtained from laundered semen stains on school uniform-type clothing, with an eight-month lag time between semen deposition and laundering, despite multiple washes and stains from two semen donors. These data emphasise the need to recover and examine the clothing of victims for semen and DNA evidence, even if the clothing has been stored for several months or washed multiple times since the sexual offence took place.