ABSTRACT
BACKGROUND: Over the past decade, long-term use of prescription opioids for chronic non-cancer pain has risen globally despite the associated risks. Most opioid users receive their first prescription in primary care. AIM: To investigate the perspective of patients who are long-term opioid users in primary care regarding the role of healthcare providers (HCPs) in their prolonged opioid use. DESIGN AND SETTING: Semi-structured interviews in Dutch primary care. METHOD: We recruited patients who were long-term users of opioids for chronic non-cancer pain from seven community pharmacies in the Netherlands. In-depth, semi-structured interviews focused on patients' experiences with long-term opioid use, access to opioids, and the guidance of their HCPs (primarily their GPs and pharmacists). A directed content analysis was conducted on the transcribed interviews using NVivo. RESULTS: Participants (n = 25) described ways in which HCPs impacted their long-term use of opioids. These encompassed the initiation of treatment, chronic use of opioids, and discontinuation of treatment. Participants stressed the need for risk counselling during initial prescribing, ongoing medication evaluations including tapering conversations, and more support from their HCP during a tapering attempt. CONCLUSION: Patients' perspectives illustrate the important role of HCPs across the spectrum of opioid use - from initiation to tapering. The results of this study underscore the importance of clear risk counselling starting at initial prescribing, repeated medication assessments throughout treatment, addressing tapering at regular intervals, and strong support during tapering. These insights carry significant implications for clinical practice, emphasising the importance of informed and patient-centred care when it comes to opioid use for chronic non-cancer pain management.
Subject(s)
Analgesics, Opioid , Chronic Pain , Primary Health Care , Qualitative Research , Humans , Netherlands , Analgesics, Opioid/therapeutic use , Male , Female , Chronic Pain/drug therapy , Middle Aged , Adult , Aged , Practice Patterns, Physicians' , Opioid-Related DisordersABSTRACT
BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486.
Subject(s)
Anti-Infective Agents , Dermatitis, Atopic , Eczema , Anti-Infective Agents/therapeutic use , Baths , Child , Dermatitis, Atopic/drug therapy , Eczema/drug therapy , Humans , Pruritus/drug therapy , Staphylococcus aureusABSTRACT
BACKGROUND: In the UK, about 14% of community-dwelling adults aged 65 and over are estimated to be at risk of malnutrition. Screening older adults in primary care and treating those at risk may help to reduce malnutrition risk, reduce the resulting need for healthcare use and improve quality of life. Interventions are needed to raise older adults' risk awareness, offer relevant and meaningful strategies to address risk and support general practices to deliver treatment and support. METHODS: Using the Person-based Approach and input from Patient and Public Involvement representatives, we developed the 'Eat well, feel well, stay well' intervention. The intervention was optimised using qualitative data from think aloud and semi-structured process evaluation interviews with 23 and 18 older adults respectively. Positive and negative comments were extracted to inform rapid iterative modifications to support engagement with the intervention. Data were then analysed thematically and final adjustments made, to optimise the meaningfulness of the intervention for the target population. RESULTS: Participants' comments were generally positive. This paper focuses predominantly on participants' negative reactions, to illustrate the changes needed to ensure that intervention materials were optimally relevant and meaningful to older adults. Key factors that undermined engagement included: resistance to the recommended nutritional intake among those with reduced appetite or eating difficulties, particularly frequent eating and high energy options; reluctance to gain weight; and a perception that advice did not align with participants' specific personal preferences and eating difficulties. We addressed these issues by adjusting the communication of eating goals to be more closely aligned with older adults' beliefs about good nutrition, and acceptable and feasible eating patterns. We also adjusted the suggested tips and strategies to fit better with older adults' everyday activities, values and beliefs. CONCLUSIONS: Using iterative qualitative methods facilitated the identification of key behavioural and contextual elements that supported engagement, and issues that undermined older adults' engagement with intervention content. This informed crucial revisions to the intervention content that enabled us to maximise the meaningfulness, relevance and feasibility of the key messages and suggested strategies to address malnutrition risk, and therefore optimise engagement with the intervention and the behavioural advice it provided.
Subject(s)
Malnutrition , Quality of Life , Aged , Communication , Humans , Independent Living , Malnutrition/prevention & control , Qualitative ResearchABSTRACT
BACKGROUND: To monitor the time elapsed since patient arrival in the emergency department, Trauma Services at the study institution installed a large digital stopwatch timer placed at the head of each trauma bay on June 5, 2017. This quality improvement endeavor became an essential component of performance evaluation. OBJECTIVE: The purpose of the study is to measure the impact of trauma bay time clocks on emergency department length of stay. METHODS: This is a retrospective before-and-after study of trauma activation patients between June 2015 and May 2019. Two 24-month intervals were compared before and after installation of time clocks. RESULTS: In full activation patients, outcomes of emergency department length of stay ≤50 min (39.2% vs. 61.7%, p < .001) and time to transfer to intensive care unit ≤56 min (45.3% vs. 55.1%, p = .002) were significantly favorable in the postimplementation phase. Time to first computed tomography scan and time to first operating room from arrival to the emergency department were comparable between both phases. For limited activation patients, positive changes were noted in emergency department length of stay ≤87 min (41.4% vs. 60.6%, p < .001), time to first computed tomography scan ≤32 min (47.7% vs. 53.0%, p = .015), and time to transfer to intensive care unit ≤74 min (50.2% vs. 57.2%, p = .008). Time to first operating room remained comparable between two periods. CONCLUSIONS: The study institution improved their provision of immediate care by using time clocks in trauma bays. This is a simple and cost-effective intervention and may benefit similar institutions.
Subject(s)
Emergency Service, Hospital , Length of Stay , Humans , Intensive Care Units , Operating Rooms , Retrospective StudiesABSTRACT
None: Genitourinary syndrome of menopause (GSM; previously known as vulvovaginal atrophy or atrophic vaginitis) involves symptoms of vaginal dryness, burning, and itching as well as dyspareunia, dysuria, urinary urgency, and recurrent urinary tract infections. It is estimated that nearly 60% of women in menopause experience GSM but the majority of these women do not bring up this concern with their health care provider. Studies also show that only 7% of health care providers ask women about this condition. This may be due to embarrassment or thinking this is a normal part of aging, both by patients and health care providers. This condition is progressive and may affect many aspects of a woman's physical, emotional, and sexual health. This article is intended to address the signs, symptoms, and significant impact this condition can have for women and help health care providers be more comfortable knowing how to ask about GSM, diagnosis it, and review the various treatment options that are available.
Subject(s)
Female Urogenital Diseases , Menopause , Vaginal Diseases , Atrophy , Female , Female Urogenital Diseases/etiology , Humans , SyndromeABSTRACT
Positive outcomes for psychological and physiological health have resulted from a nature experience. However, evidence is limited for nature-based interventions and their effect on a cancer population. The purpose of this mixed-methods study was to determine if incorporating the One Nature Challenge (ONC) into a ten-week group exercise program (WE-Can) for individuals living with cancer could offer additional psychological and/or physiological benefits to those previously observed in WE-Can. For this study, two separate ONCs were implemented throughout two seasons (summer and winter) to formulate a ONC group (n = 18; 60 ± 12yrs). Previous WE-Can graduates were used as a control group (n = 160; 59 ± 11yrs) for this study. Psychological and physiological assessments were administered in a pre- and post-test. In addition, nature relatedness (NR; ones' relationship with nature) was measured at the beginning, middle, and end of WE-Can. Following five weeks, the ONC began and participants tracked the days they experienced nature for at least thirty-minutes (24 ± 6 days), for a thirty-day period. The ONC finished concurrently with WE-Can where post-evaluations and focus groups were administered immediately following. No additional gain in overall health was found between groups. However, aerobic fitness and fatigue significantly improved for the ONC group. This was supported by frequent activities and self-reported restoration of the mind while experiencing nature. In conclusion, the lack of overall improvement could be limited by sample size and the high level of NR prior to ONC, indicating participants were already 'one with nature.'
ABSTRACT
IMPORTANCE: Although limited effective and affordable treatment options exist for hidradenitis suppurativa, recent studies describe the effectiveness of a medical therapy, infliximab, for the treatment of hidradenitis suppurativa. Cost-saving biosimilar alternatives have recently become available, but no data currently exist on their safety and effectiveness. OBJECTIVE: To evaluate the effectiveness of infliximab-abda vs infliximab administration associated with the treatment of hidradenitis suppurativa. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study identified patients treated with infliximab or infliximab-abda between 2016 and 2020 at the dermatology clinic at the University of North Carolina at Chapel Hill. The study population included patients who met the clinical criteria for hidradenitis suppurativa and had received a continuous dose of infliximab or infliximab-abda for at least 10 weeks. In total, 62 potential participants were identified using clinical tracking lists on the electronic medical records, and 34 participants were included in the final analysis. EXPOSURES: Patients who started receiving infliximab or infliximab-abda were clinically tracked for a minimum of 10 weeks using the electronic medical record system, beginning at the time of drug initiation. Patients received loading doses of 10 mg/kg at weeks 0, 2, and 6, and then treatment was continued with a maintenance dose administered every 4 to 8 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was Hidradenitis Suppurativa Clinical Response, defined as at least 50% decrease in inflammatory nodule count without any increase in number of abscesses or draining sinuses. RESULTS: Of 34 participants, 20 comprised the infliximab treatment group (mean [SD] age, 42.2 [13.2] years; 17 women [85%]), and 14 comprised the infliximab-abda treatment group (mean [SD] age, 35.5 [10.9] years; 13 women [93%]). The proportions of patients achieving a Hidradenitis Suppurativa Clinical Response were 71% (10 patients) in the infliximab-abda and 60% (12 patients) in the infliximab treatment group, which were not significantly different (P = .47). CONCLUSIONS AND RELEVANCE: This cohort study found that both infliximab administration and infliximab-abda administration were associated with similar and significant improvement in disease as measured by the Hidradenitis Suppurativa Clinical Response. Infliximab-abda is likely a reasonable treatment option for hidradenitis suppurativa, and further research is warranted.
Subject(s)
Hidradenitis Suppurativa , Adult , Cohort Studies , Female , Hidradenitis Suppurativa/complications , Hidradenitis Suppurativa/drug therapy , Humans , Infliximab/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. DESIGN: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. SETTING: 76 general practices in the United Kingdom. PARTICIPANTS: 622 people with treated but poorly controlled hypertension (>140/90 mm Hg) and access to the internet. INTERVENTIONS: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. MAIN OUTCOME MEASURES: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. RESULTS: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, 12; 95% confidence interval £6 to £29) per mm Hg reduction. CONCLUSIONS: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. TRIAL REGISTRATION: ISRCTN13790648.
Subject(s)
Blood Pressure Monitoring, Ambulatory/methods , Blood Pressure/physiology , Hypertension/therapy , Self-Management , Telemedicine/methods , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Blood Pressure Monitoring, Ambulatory/economics , Blood Pressure Monitoring, Ambulatory/standards , Female , General Practice/methods , Humans , Male , Middle Aged , United KingdomABSTRACT
BACKGROUND: Increasing physical activity, improving diet, and performing brain training exercises are associated with reduced cognitive decline in older adults. OBJECTIVE: In this paper, we describe a feasibility trial of the Active Brains intervention, a web-based digital intervention developed to support older adults to make these 3 healthy behavior changes associated with improved cognitive health. The Active Brains trial is a randomized feasibility trial that will test how accessible, acceptable, and feasible the Active Brains intervention is and the effectiveness of the study procedures that we intend to use in the larger, main trial. METHODS: In the randomized controlled trial (RCT), we use a parallel design. We will be conducting the intervention with 2 populations recruited through GP practices (family practices) in England from 2018 to 2019: older adults with signs of cognitive decline and older adults without any cognitive decline. Trial participants were randomly allocated to 1 of 3 study groups: usual care, the Active Brains intervention, or the Active Brains website plus brief support from a trained coach (over the phone or by email). The main outcomes are performance on cognitive tasks, quality of life (using EuroQol-5D 5 level), Instrumental Activities of Daily Living, and diagnoses of dementia. Secondary outcomes (including depression, enablement, and health care costs) and process measures (including qualitative interviews with participants and supporters) will also be collected. The trial has been approved by the National Health Service Research Ethics Committee (reference 17/SC/0463). RESULTS: Results will be published in peer-reviewed journals, presented at conferences, and shared at public engagement events. Data collection was completed in May 2020, and the results will be reported in 2021. CONCLUSIONS: The findings of this study will help us to identify and make important changes to the website, the support received, or the study procedures before we progress to our main randomized phase III trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number 23758980; http://www.isrctn.com/ISRCTN23758980. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18929.
ABSTRACT
INTRODUCTION: A Level I trauma center routinely faced challenges with meeting data submission deadlines and frequently struggled with a backlog of cases that limited opportunities for concurrent performance improvement. To provide a validated algorithm through which registry workload could be evaluated, the study institution designed a scientific model that predicted the amount of time required for chart abstraction on a patient-by-patient basis. METHODS: As part of this quality improvement endeavor, registrars documented the amount of time required to complete each chart. A total of 600 patients' data were included by randomly selecting 150 patients from each of the 4 trauma registrars. Given that no previous study has examined the association of patient-related factors with chart abstraction time, study variables utilized to construct this predictive model were determined by the trauma program manager and the lead trauma registrar. RESULTS: Multiple linear regression demonstrated that inhospital mortality; transfer from a referring facility; hospital stay; ventilator days; and number of complications, specialty consults, injuries, blood products, and procedures were significant predictors of chart abstraction time. The equation for the regression line for the multivariate regression was as follows: Y = 38.95 + 31.28 × mortality + 15.33 × referring facility + 4.68 × complications+3.55 × hospital stay + 3.33 × consults + 2.83 × diagnoses + 2.00 × ventilator days + 1.78 × blood products + 1.09 × procedures. CONCLUSIONS: The merit of this prediction model is that it is based on patient-related variables and predicts time on a patient-by-patient basis. This innovative tool can be utilized by other trauma centers to evaluate registry productivity and identify opportunities for improvement retrospectively.
Subject(s)
Trauma Centers , Wounds and Injuries , Hospital Mortality , Humans , Length of Stay , Registries , Retrospective StudiesABSTRACT
The American College of Surgeons (ACS) mandates all trauma centers conduct individual case reviews of nonsurgical admissions when rates of allocation to this service exceed 10% of all inpatient traumas. Nonsurgical admission rates at the study institution, which is a Level I trauma center, historically exceeded this ACS criterion. In an effort to decrease nonsurgical admissions, the study institution recruited trauma nurse practitioners (TNPs) who began managing low acuity patients with oversight from trauma attending physicians. This study examines the impact of TNPs on the rate of nonsurgical admissions. A retrospective cohort study was conducted with 1,400 patients between January 2017 and October 2018. Two cohorts examined in this study included trauma patients whose care was managed by the TNPs versus those admitted under the care of hospitalists. The rate of admission to nonsurgical services (NSS) was 19.6% in 2017 and 13.9% in 2018, which yielded a significant decrease from previous years' percentages (p < .001). The average hospital length of stay was 1.17 days shorter in the TNP group, which translated into a savings of approximately $876,330 in hospital charges for the study period. Additional significant findings noted in favor of the TNP cohort were for discharge orders placed prior to noon, discharge location, and reduced time to the operating room. This TNP model proved to be successful in significantly reducing admissions to NSS and substantiated the quality of patient care provided by TNPs. Hospitals struggling to meet the ACS criterion for NSS admissions may consider implementing a similar TNP model.
Subject(s)
Hospitalization/statistics & numerical data , Nurse Practitioners/standards , Patient Admission/standards , Practice Guidelines as Topic , Trauma Centers/standards , Trauma Nursing/standards , Wounds and Injuries/nursing , Adult , Aged , Cohort Studies , Curriculum , Education, Nursing, Continuing , Female , Humans , Male , Middle Aged , Retrospective Studies , Trauma Centers/statistics & numerical data , United States , West VirginiaABSTRACT
Nurses currently disinfect their hands with antibacterial soap and hand sanitizer. This comparative, descriptive study evaluated skin bacteria at baseline and 30 days after jewelry removal in intensive care unit nurses. Identified bacteria species were: (1) Bacillus, (2) Micrococcus, (3) coagulase negative Staphylococcus, (4) Diphtheroid, ( 5) Streptococcus, and (6) nonenteric gram-negative rods. The majority of the bacteria was found on skin at baseline. Bacterial counts significantly decreased at 30 days.
Subject(s)
Hand Sanitizers , Jewelry , Bacteria , Hand , Hand Disinfection , Hospitals , HumansABSTRACT
INTRODUCTION: The rural and remote nature of many First Nations communities in Northwestern Ontario, Canada poses unique obstacles to physically accessing health care, in addition to other barriers. Indigenous peoples face similar challenges globally. First Nations communities experience significant health inequities, including cancer burden, which can be attributed to complex factors associated with colonization and Westernization. One potentially promising intervention to decrease the burden of advanced cancers is the provision of accessible, convenient and culturally sensitive cancer screening services, leading to early detection and treatment. The Wequedong Lodge Cancer Screening Program (WLCSP) was a pilot project aiming to provide cancer screening education and opportunistic cancer screening to residents from rural and remote First Nations communities while accessing health services in the urban center of Thunder Bay, Ontario, Canada. METHODS: Cancer screening education and opportunistic breast, cervical and colorectal cancer screening appointments were offered to individuals and their travel escorts already staying at Wequedong Lodge. Program uptake was determined primarily by education participation, and secondarily by client participation in screening. RESULTS: In total, the WLCSP booked 1033 appointments, with 841 being attended. Over the program's 3 years there was an increase in clients each year. Specifically, 22% (60/275) of age-eligible women completed a mammogram. Pap tests were provided to 8% (45/554) of age-eligible females. Finally, 32% (106/333) of all age-eligible service participants were given a fecal occult blood test kit. An evaluation survey (n=396) demonstrated overall client satisfaction with the program. CONCLUSION: The WLCSP aimed to provide education about, access to and uptake of cancer screening services for First Nations people from rural and remote communities in Northwestern Ontario by targeting inequalities in accessing cancer screening opportunities. Therefore, program uptake may provide helpful numerical comparisons for similar future programs globally. Other entities working to improve cancer screening rates in remote and/or rural populations and/or amongst Indigenous peoples may find consideration of the WLCSP processes, successes and challenges helpful to their efforts.
Subject(s)
Early Detection of Cancer/methods , Health Services, Indigenous/organization & administration , Indigenous Canadians , Program Evaluation , Rural Population , Aged , Female , Humans , Male , Middle Aged , Ontario/ethnology , Pilot ProjectsABSTRACT
BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is the most common skin disease of childhood and is often more severe in African American than white children. The reason for this disparity is unknown, but recent research indicates that it may be due to a combination of environmental and genetic factors. The objective of this article was to explore the relationship between measures of structural racism and residential segregation within pediatric AD. METHODS: An in-office, online survey consisting of 58 questions spanning 5 domains (demographics, in-home crowding, community crowding, air quality, and litter) was administered to a convenience sample of 201 pediatric AD patients (age 0-18 years). Survey data were geocoded and linked to a measure of structural racism (ie, residential segregation). RESULTS: African American children were more likely to live in rented homes, be in lower income families, have caregivers with lower educational attainment, and be exposed to tobacco smoke. The same factors that were associated with worse AD severity in this study were also found in published literature, emphasizing the role of social determinants of health and racial differences in AD severity. Additionally, this study found that living in highly segregated communities was more likely to be associated with severe AD in African American children. CONCLUSIONS: Consistent with reported literature, socioeconomic status, race, and the physical environment appear to affect AD severity. This investigation adds structural racism as an important community characteristic that likely has significant effects on AD severity for African American Children.
Subject(s)
Black or African American , Dermatitis, Atopic/ethnology , Racism , Air Pollution , Child , Crowding , Demography , Female , Garbage , Humans , Male , Risk Factors , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila melanogaster Using transgenic flies that exclusively express Flag-tagged SMN from its native promoter, we previously found that Gemin2, Gemin3, Gemin5, and all nine classical Sm proteins, including Lsm10 and Lsm11, co-purify with SMN. Here, we show that CG2941 is also highly enriched in the pulldown. Reciprocal co-immunoprecipitation reveals that epitope-tagged CG2941 interacts with endogenous SMN in Schneider2 cells. Bioinformatic comparisons show that CG2941 shares sequence and structural similarity with metazoan Gemin4. Additional analysis shows that three other genes (CG14164, CG31950 and CG2371) are not orthologous to Gemins 6-7-8, respectively, as previously suggested. In D.melanogaster, CG2941 is located within an evolutionarily recent genomic triplication with two other nearly identical paralogous genes (CG32783 and CG32786). RNAi-mediated knockdown of CG2941 and its two close paralogs reveals that Gemin4 is essential for organismal viability.
Subject(s)
Drosophila Proteins/genetics , SMN Complex Proteins/genetics , Animals , Binding Sites , Drosophila Proteins/chemistry , Drosophila Proteins/metabolism , Drosophila melanogaster , Evolution, Molecular , Protein Binding , SMN Complex Proteins/chemistry , SMN Complex Proteins/metabolismABSTRACT
Hereditary spastic paraplegias (HSP) are a rare heterogeneous group of inherited neurodegenerative diseases characterized by progressive lower extremity spasticity and weakness. Mutations of the kinesin family member 5A (KIF5A) gene lead to a spectrum of phenotypes ranging from spastic paraplegia type 10 to Charcot-Marie Tooth Disease type 2. We report the second known case of a mutation in the KIF5A gene at c.610C>T presenting with HSP plus an axonal sensorimotor neuropathy.
ABSTRACT
INTRODUCTION: Pathogenic mutations and variants of uncertain significance (VUS) occur in BRCA1/2 genes. METHODS: Records of women with a pathogenic mutation or VUS in BRCA1/2 treated between 2008 and 2017 were reviewed. RESULTS: One hundred and ten women were included. Mean age was 47. A pathogenic mutation or a VUS in BRCA1/2 was detected in 85 (77%) and 25 (23%) patients, respectively. The rate of risk reducing mastectomy (RRM) was 50% in women with a pathogenic mutation and 30% in women with a VUS (Pâ¯=â¯0.232). Among women with breast cancer, 65% with a pathogenic mutation and 40% with a VUS underwent RRM. Over 50% of women with a pathogenic mutation in BRCA1/2 chose surveillance over operation. DISCUSSION: There was no statistical difference in the rate of RRM among women with a pathogenic mutation or a VUS in BRCA1/2 in our population. The majority of high risk women in our study chose to forgo RRM for breast cancer screening.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/surgery , Decision Making , Mastectomy/statistics & numerical data , Adolescent , Adult , Aged , BRCA1 Protein , BRCA2 Protein , Female , Genetic Testing , Humans , Middle Aged , Mutation , Risk Management , Risk Reduction Behavior , Watchful WaitingABSTRACT
CONTEXT: - Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. OBJECTIVE: - To provide updated, practical guidelines for the pathologic diagnosis of MM. DATA SOURCES: - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. CONCLUSIONS: - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.
Subject(s)
Adenocarcinoma/diagnosis , Lung Neoplasms/diagnosis , Lung/pathology , Mesothelioma/diagnosis , Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Consensus , Cytodiagnosis/methods , Diagnosis, Differential , Humans , Immunohistochemistry , Lung/chemistry , Lung Neoplasms/metabolism , Mesothelioma/metabolism , Public OpinionABSTRACT
OBJECTIVE: To explore perceptions of illness, the decisions to consult and the acceptability of delayed antibiotic prescriptions and self-help treatments for respiratory tract infections (RTIs). DESIGN: Qualitative semistructured interview study. SETTING: UK primary care. PARTICIPANTS: 20 adult patients who had been participating in the 'PIPS' (Pragmatic Ibuprofen Paracetamol and Steam) trial in the South of England. METHOD: Semistructured telephone interviews were conducted with participants to explore their experiences and views on various treatments for RTI. RESULTS: Participants had concerns about symptoms that were not clinically serious and were mostly unaware of the natural history of RTIs, but were aware of the limitations of antibiotics and did not expect them with every consultation. Most viewed delayed prescriptions positively and had no strong preference over which technique is used to deliver the delayed antibiotic, but some patients received mixed messages, such as being told their infection was viral then being given an antibiotic, or were sceptical about the rationale. Participants disliked self-help treatments that involved taking medication and were particularly concerned about painkillers in combination. Steam inhalation was viewed as only moderately helpful for mild symptoms. CONCLUSION: Delayed prescribing is acceptable no matter how the delay is operationalised, but explanation of the rationale is needed and care taken to minimise mixed messages about the severity of illnesses and causation by viruses or bacteria. Better access is needed to good natural history information, and the signs and symptoms requiring or not requiring general practitioner advice. Significant concerns about paracetamol, ibuprofen and steam inhalation are likely to need careful exploration in the consultation.
Subject(s)
Acetaminophen/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Anti-Bacterial Agents/therapeutic use , Ibuprofen/therapeutic use , Patient Acceptance of Health Care , Respiratory Tract Infections/drug therapy , Adult , Aged , England , Female , Health Knowledge, Attitudes, Practice , Humans , Interviews as Topic , Male , Middle Aged , Practice Patterns, Physicians' , Primary Health Care , Qualitative Research , Self-Management , Young AdultABSTRACT
BACKGROUND: Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. DESIGN: Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. SETTING: Primary care general practices in the UK. PARTICIPANTS: Patients with a body mass index of ≥ 30 kg/m2 (or ≥ 28 kg/m2 with risk factors) identified from general practice records, recruited by postal invitation. INTERVENTIONS: Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). MAIN OUTCOME MEASURES: The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. RESULTS: A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81%; control, n = 227; POWeR+F, n = 221; POWeR+R, n = 218). The control group maintained nearly 3 kg of weight loss per person (mean weight per person: baseline, 104.4 kg; 6 months, 101.9 kg; 12 months, 101.7 kg). Compared with the control group, the estimated additional weight reduction with POWeR+F was 1.5 kg [95% confidence interval (CI) 0.6 to 2.4 kg; p = 0.001] and with POWeR+R was 1.3 kg (95% CI 0.34 to 2.2 kg; p = 0.007). By 12 months the mean weight loss was not statistically significantly different between groups, but 20.8% of control participants, 29.2% of POWeR+F participants (risk ratio 1.56, 95% CI 0.96 to 2.51; p = 0.070) and 32.4% of POWeR+R participants (risk ratio 1.82, 95% CI 1.31 to 2.74; p = 0.004) maintained a clinically significant 5% weight reduction. The POWeR+R group had fewer individuals who reported doing another activity to help lose weight [control, 47.1% (64/136); POWeR+F, 37.2% (51/137); POWeR+R, 26.7% (40/150)]. The incremental cost to the health service per kilogram weight lost, compared with the control group, was £18 (95% CI -£129 to £195) for POWeR+F and -£25 (95% CI -£268 to £157) for POWeR+R. The probability of being cost-effective at a threshold of £100 per kilogram was 88% and 98% for POWeR+F and POWeR+R, respectively. POWeR+R was dominant compared with the control group. No harms were reported and participants using POWeR+ felt more enabled in managing their weight. The qualitative studies documented that POWeR+ was viewed positively by patients and that health-care professionals generally enjoyed supporting patients using POWeR+. STUDY LIMITATIONS: Maintenance of weight loss after 1 year is unknown. FUTURE WORK: Identifying strategies for longer-term engagement, impact in community settings and increasing physical activity. CONCLUSION: Clinically valuable weight loss (> 5%) is maintained in 20% of individuals using novel written materials with brief follow-up. A web-based behavioural programme and brief support results in greater mean weight loss and 10% more participants maintain valuable weight loss; it achieves greater enablement and fewer participants undertaking other weight-loss activities; and it is likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21244703. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 4. See the NIHR Journals Library website for further project information.