Barriers to and opportunities for advancing racial equity in cervical cancer screening in the United States.

BACKGROUND: In the United States (U.S.), racially minoritized people have higher rates of cervical cancer morbidity and mortality compared to white individuals as a result of racialized structural, social, economic, and health care inequities. However, cervical cancer screening guidelines are based on studies of predominately white individuals and do not substantially discuss or address racialized cervical cancer inequities and their social determinants, including racism. METHODS: We conducted in-depth interviews with health care providers (N = 30) and key informants with expertise in health equity (N = 18). We utilized semi-structured interview guides that addressed providers' views and experiences delivering cervical cancer screening to racially minoritized individuals and key informants' recommendations for advancing racial equity in the development and implementation of cervical cancer screening guidelines. Interviews were analyzed using a template style thematic analysis approach involving deductive and inductive coding, memo writing, and matrix analysis for theme development. RESULTS: Most health care providers adopted a universal, one-size-fits-all approach to cervical cancer screening with the stated goal of ensuring racial equality. Despite frequently acknowledging the existence of racialized cervical cancer inequities, few providers recognized the role of social inequities in influencing them, and none discussed the impact of racism. In contrast, key informants overwhelmingly recommended that providers adopt an approach to cervical cancer screening and follow-up care that recognizes the role of racism in shaping racialized cervical cancer and related social inequities, is developed in partnership with racially minoritized communities, and involves person-centered, structurally-competent, and trauma-informed practices that address racially minoritized peoples' unique lived experiences in historical and social context. This racism-conscious approach is not to be confused with race-based medicine, which is an essentialist and racist approach to health care that treats race as a biological variable rather than as a social and political construct. CONCLUSIONS: Developers and implementers of cervical cancer screening guidelines should explicitly recognize and address the impact of racism on cervical cancer screening, follow-up care, and outcomes, meaningfully incorporate racially minoritized communities' perspectives and experiences, and facilitate provider- and institutional-level practices that foster racial equity in cervical cancer.

Colorectal cancer care in the COVID-19 era: outcomes from a 'mixed site' model.

INTRODUCTION: The COVID-19 pandemic has presented many challenges to colorectal cancer (CRC) care. Many organisations opted to perform CRC resections in 'cold' sites. Infrastructure in Northumbria Healthcare NHS Foundation Trust (NHCT) necessitated co-locating CRC care with 'hot' COVID streams but with additional precautions. This study aimed to evaluate that approach for a consecutive series of CRC cases, diagnosed before and during the COVID-19 pandemic. METHODS: A prospectively populated data set of CRC patients diagnosed between 1 April 2019 and 30 September 2020 was used. Patients presenting before 1 April 2020 were considered 'pre-COVID' and those presenting subsequently as 'COVID era'. RESULTS: Some 344 cases were diagnosed in the 12 months 'pre-COVID' and 166 in the 6 months of the 'COVID era'. The median numbers of days from referral to diagnosis (21 vs 20, p=0.373) and operation (63 vs 61, p=0.208) were unchanged. The 'COVID era' saw an increase in the proportion of radiological diagnoses (39.5% vs 53.0%, p=0.004) with an associated decrease in endoscopic diagnoses (56.7% vs 45.8%, p=0.021). Rates of inoperable (1.5% vs 1.2%, p=0.821), obstructing (11.0% vs 16.2%, p=0.272) and perforated tumours (0.6% vs 1.5%, p=0.492) remained the same. One patient developed COVID-19 perioperatively. Rates of laparoscopic operation (59.5% vs 61.8%, p=0.751), anastomotic leak (6.4% vs 5.9%, p=0.891), re-operative surgery (10.4% vs 4.4%, p=0.138), primary stoma (40.5% vs 32.4%, p=0.244) and 90-day mortality (0.6% vs 1.5%, p=0.492) did not change. CONCLUSIONS: With appropriate infection control measures, it may be safe to continue providing standard elective and urgent CRC care without access to a 'COVID clean' site.

Stoma reversal in functional bowel disease: managing patient choice.

INTRODUCTION: This study aims to assess the rate of stoma reversal in patients who have undergone stoma formation with permanent intent for functional bowel disorder. We also assessed the incidence of malignancy in defunctioned bowel. METHODS: This is a retrospective study of the outcomes of patients undergoing planned permanent stoma formation for functional bowel disorder over a 10-year period at a single tertiary centre. RESULTS: Of 92 patients included in the study, 11 (12%) requested and underwent stoma reversal following stoma formation for functional bowel disorder. Of 84 patients with defunctioned bowel left in situ, two (2%) developed bowel malignancy during our study period. CONCLUSIONS: Stoma formation may be necessary for patients with incontinence and constipation when conservative treatments fail. Some patients have very firm views about the need for a stoma, but a significant proportion of patients do not cope with a stoma and request reversal, therefore patient selection and pre-procedure counselling are important. The risk of developing malignant disease in the defunctioned colon is potentially significant, and consideration should be given to appropriate surveillance in this group of patients. Evidence for stoma formation in functional gastrointestinal disorders is lacking; this study reports outcomes in a large cohort of patients over a long period, and highlights areas where further research and practice guidelines are needed. If large numbers of patients are undergoing stoma reversal posing significant mortality and morbidity risks, this suggests that patient selection and preoperative counselling need refinement.

Knowledge and perceptions of the COVID-19 pandemic among patients with myasthenia gravis.

BACKGROUND: Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID-19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID-19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves. METHODS: This is a prospective online survey study at large academic practice. All patients with a neuromuscular junction disorder diagnosis code in the Duke Health System were invited to participate. RESULTS: One thousand eight hundred and forty eight patients were approached to participate and 75 completed the survey between 16 April 2020 and 28 May 2020. The most frequently used information sources were non-presidential federal government (75%), state government (57%), local healthcare provider (37%), and television news (36%). Non-presidential federal government (80%), local healthcare providers (55%), state government (33%), and patient support organizations (29%) were considered the most trusted information sources. Thirty-three (44%) of survey responders had attended a telemedicine visit. Patients were taking recommended precautions during the pandemic and remained very concerned (69%) about COVID-19. Generalized Anxiety Disorder-7 scores were moderate-severe in 20% of responders. CONCLUSIONS: Healthcare providers, the government, and patient organizations play a critical role in communicating with the MG patient community. Use of targeted messaging strategies by these groups to convey accurate information may increase effectiveness and lead to more informed patients with reduced anxiety.

Surgery for constipation: systematic review and practice recommendations: Results V: Sacral Nerve Stimulation.

AIM: To assess the outcomes of sacral nerve stimulation in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Seven articles were identified, providing data on outcomes in 375 patients. Length of procedures and length of stay was not reported. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 13 and 34%, with overall device removal rate between 8 and 23%. Although inconsistently reported, pooled treatment success was typically 57-87% for patients receiving permanent implants, although there was significant variation between studies. Patient selection was inconsistently documented. No conclusions could be drawn regarding particular phenotypes that responded favourably or unfavourably to sacral nerve stimulation. CONCLUSION: Evidence supporting sacral nerve stimulation is derived from poor quality studies. Three methodologically robust trials are have reported since this review and all have all urged greater caution.

Routine versus selective histological examination after cholecystectomy to exclude incidental gallbladder carcinoma.

Introduction Gallstone disease is treated commonly with cholecystectomy. Malignant disease of the gallbladder may present similarly and has a poor prognosis. It is common for cholecystectomy specimens to be sent for histological examination to exclude malignancy. However, the incidence of incidental gallbladder carcinoma (IGBC) is low and it has therefore been suggested that macroscopic inspection of the gallbladder by the surgeon, followed by selective histological examination of abnormal specimens, may be safe and cost saving. Methods All cholecystectomies performed between 1 May 2003 and 1 September 2009 were identified from clinical coding. Pathology records were used to identify gallbladder malignancies; these were searched manually to identify IGBC. Pathology reports and case notes were cross-referenced to determine whether there were macroscopic abnormalities present. Annual cost savings were estimated by comparing the number of gallbladder specimens over one year (May 2013 - April 2014) with the total number of cholecystectomies performed in that time. Results Of 4,776 cholecystectomies identified, 12 (0.25%) were cases of IGBC. These cases had a higher median age (68 vs 54 years, p<0.001) and a higher proportion were emergency operations (50% vs 12%, p<0.001). All cases had some form of macroscopic abnormality, most commonly wall thickening (n=6, 50%). Only two cases (17%) had a visible tumour present. Conclusions All cases of IGBC in this study had a macroscopically abnormal gallbladder. Our findings suggest it is safe to adopt a selective approach to histological examination. Savings of almost £20,500 per annum have been achieved.

Healthcare professionals' views on two computer-based decision aids for women choosing mode of delivery after previous caesarean section: a qualitative study.

OBJECTIVE: To explore healthcare professionals' views about decision aids, developed by the DiAMOND study group, for women choosing mode of delivery after a previous caesarean section. DESIGN/METHODS: A qualitative focus group study. Data were analysed thematically. SETTING: Two city maternity units, surrounding community midwife units and general practitioner (GP) practices in southwest England. SAMPLE: Twenty-eight healthcare professionals, comprising obstetricians, hospital and community midwives and GPs, who participated in six focus groups. RESULTS: Participants were generally positive about the decision aids. Most thought they should be implemented during early pregnancy in the community, but should be accessible throughout pregnancy, with any arising questions discussed with an obstetrician nearer to term. Perceived barriers to implementation included service issues (e.g. time pressure, cost and access), computer issues (e.g. computer literacy) and people issues (e.g. women's prior delivery preferences and clinician preference). Facilitators to implementation included access to more standardised and reliable information and empowerment of the user. Self-accessing the aids, increased awareness of decision aids among healthcare professionals and incorporation of aids into usual care were suggested as possible ways to improve implementation success. CONCLUSIONS: This study gives insight into healthcare professionals' views on the role of decision aids for women choosing a mode of delivery after a prior caesarean section. It highlights potential obstacles to their implementation and ways to address these. Such aids could be a useful adjunct to current antenatal care.

Concentrations of some metabolites in the breath of healthy children aged 7-18 years measured using selected ion flow tube mass spectrometry (SIFT-MS).

Using selected ion flow tube mass spectrometry (SIFT-MS), measurements have been made of the levels of several metabolites in the exhaled breath of 200 healthy school children. Thus, concentration distributions of each metabolite have been obtained for the first time in the paediatric age range. The median values (in parentheses) of the concentrations in parts per billion, ppb, were ammonia (628), acetone (297), methanol (193), ethanol (187), isoprene (37), propanol (16), acetaldehyde (23) and pentanol (15). Hydrogen cyanide was not present in the breath above the detection limit of 2 ppb in the majority of subjects. The water vapour level (humidity) of the breath samples was routinely measured as a check on the sample integrity. Such data are essential if SIFT-MS breath analyses are to be used as a clinical tool to aid diagnosis and/or as a monitor of disease in children. The levels of metabolites usually followed a log-normal distribution and the levels of some compounds were similar to those obtained previously in adults. Lower values were found in the levels of acetone, ammonia, methanol and isoprene. There were no major variations in relation to gender. Some metabolites showed significant variation in relation to age and body mass index. To our knowledge, these are the first measurements of exhaled mouth breath pentanol levels. The median ammonia levels in mouth-exhaled breath of these children decreased with age, whereas in older adults, ammonia has been shown to increase with age. Breath acetone levels were significantly increased for those who had not eaten for more than 6 h prior to providing the breath sample, although dietary control was not a mandatory aspect of the protocol.

The Mental Capacity Act 2005 and its impact on dental practice.

In 1995, the Law Commission was given the task of investigating 'the adequacy of legal and other procedures for decision-making on behalf of mentally incapacitated adults'. It concluded that the law was fragmented and confusing and called for a single statute to govern decision-making on behalf of mentally incapable adults regarding welfare, healthcare and financial matters. There followed a 15 year period of consultation, resulting in the new Mental Capacity Act 2005 which came into full force in October 2007. Dentists who administer treatment to patients suffering from mental incapacity due to dementia, learning disabilities, depression, brain injury and other forms of mental disorder, need to be familiar with the Act and its accompanying Code of Practice. This article looks at how the new Act impacts upon the treatment of incapable patients by dentists, whether they are in general surgery, community or hospital settings. In particular, this article focuses on the provisions of the Act which relate to how and when capacity should be assessed prior to the dentist carrying out treatment and the consequences of a finding of incapacity for both the dentist and the patient in his or her care.

Women's experience of decision making about mode of delivery after a previous caesarean section: the role of health professionals and information about health risks.

OBJECTIVE: To explore women's experiences of decision making about mode of delivery after previous caesarean section. DESIGN: A qualitative interview study. SETTING: Two city maternity units in southwest England and Eastern Scotland. SAMPLE: Twenty-one women who had recently delivered a baby and whose previous child was delivered by caesarean section. METHODS: Semi-structured interviews analysed using the framework approach. MAIN OUTCOME MEASURES: Women's views on the influence of uncertainty on decision making, issues concerning information provision and decision-making roles. RESULTS: Experiences of decision making varied considerably. Some women were certain about choosing either vaginal birth after caesarean or repeat elective caesarean section, others were very uncertain and for some this uncertainty persisted after the birth. Information was most commonly provided by hospital doctors (mainly consultants) and more often related to procedural issues rather than possible health risks and benefits. Women felt they had to actively seek information rather than it being provided routinely. Most women were able to make their own decision about mode of delivery. Health professionals generally took a supportive role whichever mode of delivery was chosen. Although many women were comfortable with this approach, some felt they would have liked more guidance. CONCLUSION: On the whole, women experienced having control over the decision about planned mode of delivery. For many, making this decision was difficult and for some it was the cause of prolonged anxiety. Women were often making the decision without being provided with comprehensive and specific information about possible health risks and benefits. We are currently conducting a randomised controlled trial to investigate whether access to a decision aid is beneficial to women in this situation.

Designing a low-cost pollution prevention plan to pay off at the University of Houston.

The University of Houston is located just south of downtown Houston, TX. Many different chemical substances are used in scientific research and teaching activities throughout the campus. These activities generate a significant amount of waste materials that must be discarded as regulated hazardous waste per U.S. Environmental Protection Agency (EPA) rules. The Texas Commission on Environmental Quality (TCEQ) is the state regulatory agency that has enforcement authority for EPA hazardous waste rules in Texas. Currently, the University is classified as a large quantity generator and generates >1000 kg per month of hazardous waste. In addition, the University has experienced a major surge in research activities during the past several years, and overall the quantity of the hazardous waste generated has increased. The TCEQ requires large quantity generators to prepare a 5-yr Pollution Prevention (P2) Plan, which describes efforts to eliminate or minimize the amount of hazardous waste generated. This paper addresses the design and development of a low-cost P2 plan with minimal implementation obstacles and strong payoff potentials for the University. The projects identified can be implemented with existing University staff resources. This benefits the University by enhancing its environmental compliance efforts, and the disposal cost savings can be used for other purposes. Other educational institutions may benefit by undertaking a similar process.

European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes.

BACKGROUND: Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of beta-cell NAD depletion. We aimed to assess whether high dose nicotinamide prevents or delays clinical onset of diabetes in people with a first-degree family history of type 1 diabetes. METHOD: We did a randomised double-blind placebo-controlled trial of nicotinamide in 552 relatives with confirmed islet cell antibody (ICA) levels of 20 Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1.2 g/m2) or placebo for 5 years. Random allocation was done with a pseudorandom number generator and we used size balanced blocks of four and stratified by age and national group. Primary outcome was development of diabetes, as defined by WHO criteria. Analysis was done on an intention-to-treat basis. FINDINGS: There was no difference in the development of diabetes between the treatment groups. Of 159 participants who developed diabetes in the course of the trial, 82 were taking nicotinamide and 77 were on placebo. The unadjusted hazard ratio for development of diabetes was 1.07 (95% CI 0.78-1.45; p=0.69), and the hazard ratio adjusted for age-at-entry, baseline glucose tolerance, and number of islet autoantibodies detected was 1.01 (0.73-1.38; p=0.97). Of 168 (30.4%) participants who withdrew from the trial, 83 were on placebo. The number of serious adverse events did not differ between treatment groups. Nicotinamide treatment did not affect growth in children or first-phase insulin secretion. INTERPRETATION: Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.

Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis.

Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat.

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.

Utilizing daily interferon (alpha 2b) and ribavirin combination therapy in chronic hepatitis C: a preliminary report.

UNLABELLED: The optimal dose, frequency and duration of interferon alpha 2b and ribavirin combination for the treatment of chronic hepatitis C is still not clear. Preliminary hepatitis C virus kinetic studies have suggested that daily interferon (IFN) is more advantageous than less frequent administration. This report documents the preliminary findings of an investigative protocol to evaluate the efficacy of long-term (12 month), daily IFN alpha 2b and ribavirin combination therapy for chronic hepatitis C patients, who have either relapsed (relapsers) or not responded (non-responders) to previous IFN therapy. METHODS: 25 non-cirrhotic HCV patients were enrolled in an attempt to treat protocol. Patients were administered 3 million units (MU) IFN alpha 2b subcutaneously (SQ) and ribavirin 1000-1200 mg PO on a daily basis. RESULTS: Four patients were removed from the protocol because of noncompliance. The remaining 21 patients (10 relapsers, 11 non-responders) were evaluated at the end of their 12th week of treatment. Twelve patients (57%) became HCV-RNA negative and nine patients (43%) remain positive at the end of this period. CONCLUSION: Although further studies on larger patient populations are necessary, our preliminary data suggests that daily IFN alpha 2b and ribavirin treatment is highly effective, especially among patients who have relapsed from previous IFN treatment.

A comparison of role expectations and communication styles between transplant coordinators and transplant staff nurses.

The role of the transplant coordinator is multifaceted and demanding, requiring advanced clinical skills in addition to patient management responsibilities. Although much is known about the clinical skills of these coordinators, there is virtually no information available about their management abilities. A comparison of the beliefs of transplant coordinators and transplant staff nurses confirms that the coordinators have the role expectations and communication styles to allow them to function effectively in managing patient care as well as in working with physicians and other health professionals.

Evaluation of human astrocytoma and glioblastoma cell lines for nerve growth factor release.

Nerve growth factor (NGF) prevents degeneration of cholinergic neurons in the central nervous system (CNS), and has potential as a therapeutic treatment for Alzheimer's disease. The inability of NGF to cross the blood-brain barrier has prompted pharmacological approaches investigating peripherally administered compounds that stimulate release of endogenous NGF. This study describes the NGF-releasing properties of six human astrocytoma and glioblastoma cell lines (SW 1088, SW 1783 and CRL 1718 astrocytomas, and U-138, U-373, and T98G glioblastomas). Using a highly specific two-site ELISA for human NGF, basal NGF release could be detected in all cell lines, with the lowest level in the T98G line (approximately 80 pg NGF/ml). Cell lines tested with a variety of compounds for 24 h in serum-free media demonstrated stimulation of NGF release by distinct mechanisms. NGF levels were markedly elevated (up to 8-fold above vehicle-treated cells) when stimulated with the cytokine interleukin-1 beta (IL-1 beta). Phorbol ester stimulated NGF release 4-fold. Clenbuterol, 4-methyl catechol, and propentofylline had little activity, while 6-(4-hydroxybutyl)-2,3,5,-trimethyl-1,4,benzoquinone (TMQ), dexamethasone and 1,25-dihydroxyvitamin D3 elevated NGF levels 3-fold. These data indicate differences in the ability of human astrocytoma and glioblastoma cells to release NGF when stimulated with mechanistically distinct compounds.

Distribution of radioiodinated recombinant human nerve growth factor in primate brain following intracerebroventricular infusion.

The distribution of radioiodinated recombinant human nerve growth factor ([125I]rhNGF) was evaluated in adult cynomolgus monkeys following unilateral intracerebroventricular (icv) administration. Animals were cannulated into the right ventricle and recovered for 7 days. Monkeys were infused with 1.2 micrograms of [125I]rhNGF or [125I]rhNGF with a 140-fold excess of rhNGF. Twenty-four hours after infusion, animals were anesthetized and transcardially perfused with an aldehyde fixative. Coronal brain sections were processed for quantitative film autoradiography or for choline-acetyltransferase immunohistochemistry and then emulsion dipped. Specific radiolabel was distributed bilaterally and, with equal density, throughout the basal forebrain and was colocalized with choline acetyltransferase-positive neurons. Specific labeling was also present in the superficial ventral cortex. Nonspecific binding was observed surrounding the ventricles and lining blood vessels. These results demonstrate that unilateral icv infusion is an effective approach for delivering NGF to basal forebrain cholinergic neurons in primates and represents a viable drug delivery strategy for the therapeutic use of NGF in Alzheimer's Disease.