Lived Experiences and Fear of Cancer Recurrence Among Survivors of Localized Cutaneous Melanoma.

Importance: Most of the rapid increase in cutaneous melanoma incidence in the US has been localized disease that is treated surgically and is associated with high survival rates. However, little is known about the psychological well-being of survivors in the US. Objective: To explore the lived experiences and fear of cancer recurrence among survivors of localized cutaneous melanoma. Design, Setting, and Participants: This was a qualitative and survey-based study that used semistructured interviews and the Fear of Cancer Recurrence Inventory short form (FCRI-SF) survey tool with participants recruited from an academic dermatology practice affiliated with the University of Texas, Austin. Interviews were completed via telephone or in person from August 2021 to September 2022. Each of the 9 items in the FCRI-SF was rated on a 5-point Likert scale, scored from 0 to 4, with a maximum possible score of 36 points. Data analyses were performed from February 2022 to June 2023. Main Outcomes and Measures: Semistructured interviews were analyzed for themes and subthemes associated with the lived experiences of survivors of cutaneous melanoma. The FCRI-SF scores were tabulated, with scores of 13 or greater identifying potential cases of clinically significant fear of cancer recurrence. Results: In all, 51 participants (mean [SD] age, 49.5 [11.7] years; 34 [67%] female and 17 [33%] male) with a history of localized melanoma (stage 0-IIA) completed the interview and survey. Among them, 17 (33%) had survived a diagnosis of stage 0 melanoma, and the remainder, at least 1 invasive melanoma diagnosis (stage I-IIA). Semistructured interviews revealed several themes: (1) emotions surrounding follow-up appointments, (2) intensity of melanoma surveillance, (3) lifestyle changes regarding sun exposure, and (4) thoughts about life and death. Thirty-eight of 51 participants had an FCRI-SF score above the threshold for clinical fear of cancer recurrence. Conclusions and Relevance: This qualitative and survey-based study found that despite having an excellent prognosis, some survivors of localized melanoma, even those who had stage 0, have high rates of fear of cancer recurrence and intense survivorship experiences that affect their psychological well-being.

Condomless sex under the influence differs by class rank in college students.

OBJECTIVE: College students, particularly first-year students, are at risk for alcohol misuse and alcohol-related consequences (e.g., condomless sex). Our objective was to determine if first- and second-year students were more or less likely to report any act of condomless sex under the influence of alcohol than third- and fourth-year students. PARTICIPANTS: Participants (N = 447) were undergraduate students recruited from a private institution in Massachusetts. METHODS: Logistic regression models were used to analyze differences in reported acts of condomless sex under the influence of alcohol in the past 30 days, by class rank. RESULTS: First- and second-year students had lower odds (OR 0.40, 95% CI: 0.252-0.648) of reporting condomless sex under the influence of alcohol than third- and fourth-year students. CONCLUSIONS: Implications from these results can contribute to understanding sexually transmitted infections in the college population.

Integrating Cognitive Dysfunction Accommodation Strategies Into Behavioral Interventions for Persons on Medication for Opioid Use Disorder.

BACKGROUND: Cognitive dysfunction is disproportionately prevalent among persons with opioid use disorder (OUD). Specific domains of cognitive dysfunction (attention, executive functioning, memory, and information processing) may significantly impede treatment outcomes among patients on medication for OUD (MOUD). This limits patient's ability to learn, retain, and apply information conveyed in behavioral intervention sessions. Evidence-based accommodation strategies have been integrated into behavioral interventions for other patient populations with similar cognitive profiles as persons with OUD; however, the feasibility and efficacy of these strategies have not yet been tested among patients on MOUD in a drug treatment setting. METHODS: We conducted a series of focus groups with 25 key informants (10 drug treatment providers and 15 patients on MOUD) in a drug treatment program in New Haven, CT. Using an inductive approach, we examined how cognitive dysfunction impedes participant's ability to retain, recall, and utilize HIV prevention information in the context of drug treatment. RESULTS: Two main themes capture the overall responses of the key informants: (1) cognitive dysfunction issues and (2) accommodation strategy suggestions. Subthemes of accommodation strategies involved suggestions about particular evidence-based strategies that should be integrated into behavioral interventions for persons on MOUD. Specific accommodation strategies included: use of a written agenda, mindfulness meditation, multi-modal presentation of information, hands-on demonstrations, and a formal closure/summary of sessions. CONCLUSIONS: Accommodation strategies to compensate for cognitive dysfunction were endorsed by both treatment providers and patients on MOUD. These accommodation strategies have the potential to enhance the efficacy of behavioral interventions to reduce HIV transmission among persons on MOUD as well as addiction severity, and overdose.

CNS distribution, signalling properties and central effects of G-protein coupled receptor 4.

Information on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increase in cAMP towards acidic pH. The GPR4 antagonist NE 52-QQ57 effectively blocked GPR4-mediated cAMP accumulation (IC50 26.8 nM in HEK293 cells). In HUVEC which natively express GPR4, physiological acidification (pH 7.4-7.0) resulted in a cAMP increase by ∼55% which was completely prevented by 1 µM NE 52-QQ57. The main extracellular organic acid, l-lactic acid (LL; 1-10 mM), suppressed pH dependent activation of GPR4 in HEK293 and HUVEC cells, suggesting allosteric negative modulation. In unanaesthetised mice and rats, NE 52-QQ57 (20 mg kg-1) reduced ventilatory response to 5 and 10% CO2. In anaesthetised rats, systemic administration of NE 52-QQ57 (up to 20 mg kg-1) had no effect on hemodynamics, cerebral blood flow and blood oxygen level dependent responses. Central administration of NE 52-QQ57 (1 mM) in vagotomised anaesthetised rats did not affect CO2-induced respiratory responses. Our results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and LL. NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4.

Modelling accretion disc and stellar wind interactions: the case of Sgr A.

Sgr A* is an ideal target to study low-luminosity accreting systems. It has been recently proposed that properties of the accretion flow around Sgr A* can be probed through its interactions with the stellar wind of nearby massive stars belonging to the S-cluster. When a star intercepts the accretion disc, the ram and thermal pressures of the disc terminate the stellar wind leading to the formation of a bow shock structure. Here, a semi-analytical model is constructed which describes the geometry of the termination shock formed in the wind. With the employment of numerical hydrodynamic simulations, this model is both verified and extended to a region prone to Kelvin-Helmholtz instabilities. Because the characteristic wind and stellar velocities are in âˆ¼108 cm s-1 range, the shocked wind may produce detectable X-rays via thermal bremsstrahlung emission. The application of this model to the pericentre passage of S2, the brightest member of the S-cluster, shows that the shocked wind produces roughly a month long X-ray flare with a peak luminosity of L ≈ 4 × 1033 erg s-1 for a stellar mass-loss rate, disc number density, and thermal pressure strength of [Formula: see text], nd = 105 cm-3, and α = 0.1, respectively. This peak luminosity is comparable to the quiescent X-ray emission detected from Sgr A* and is within the detection capabilities of current X-ray observatories. Its detection could constrain the density and thickness of the disc at a distance of âˆ¼3000 gravitational radii from the supermassive black hole.

A source of artifact in the lacZ reversion assay in Escherichia coli.

The lacZ reversion assay in Escherichia coli measures point mutations that occur by specific base substitutions and frameshift mutations. The tester strains cannot use lactose as a carbon source (Lac(-)), and revertants are easily detected by growth on lactose medium (Lac(+)). Six strains identify the six possible base substitutions, and five strains measure +G, -G, -CG, +A and -A frameshifts. Strong mutagens give dose-dependent increases in numbers of revertants per plate and revertant frequencies. Testing compounds that are arguably nonmutagens or weakly mutagenic, we often noted statistically significant dose-dependent increases in revertant frequency that were not accompanied by an absolute increase in numbers of revertants. The increase in frequency was wholly ascribable to a declining number of viable cells owing to toxicity. Analysis of the conditions revealed that the frequency of spontaneous revertants is higher when there are fewer viable cells per plate. The phenomenon resembles "adaptive" or "stress" mutagenesis, whereby lactose revertants accumulate in Lac(-) bacteria under starvation conditions in the absence of catabolite repression. Adaptive mutation is observed after long incubation and might be expected to be irrelevant in a standard assay using 48-h incubation. However, we found that elevated revertant frequencies occur under typical assay conditions when the bacterial lawn is thin, and this can cause increases in revertant frequency that mimic chemical mutagenesis when treatments are toxic but not mutagenic. Responses that resemble chemical mutagenesis were observed in the absence of mutagenic treatment in strains that revert by different frameshift mutations. The magnitude of the artifact is affected by cell density, dilution, culture age, incubation time, catabolite repression and the age and composition of media. Although the specific reversion assay is effective for quickly distinguishing classes of mutations induced by potent mutagens, its utility for discerning effects of weak mutagens may be compromised by the artifact.

Major complications of epidural analgesia after surgery: results of a six-year survey.

We performed a retrospective case note review to identify the major complications of epidural analgesia occurring after surgery at our hospital. By cross-referencing the radiology, microbiology and patient information management system databases, we identified patients who had undergone either spinal magnetic resonance imaging or a lumbar puncture within 60 days of surgery in the period from January 2000 to December 2005. Review of these case notes identified six cases of epidural abscess, three of meningitis and three of epidural haematoma. Symptoms of epidural abscess or meningitis developed a median of 5 days after epidural catheter removal. Methicillin-resistant Staphylococcus aureus was the predominant pathogen. Epidural haematoma symptoms developed while the epidural catheter was in place. These symptoms were initially attributed to the epidural infusion. Diagnostic delays contributed to adverse neurological outcome in three patients. This study suggests that leg weakness is a critical monitor of spinal cord health. A national database is needed to establish a more accurate estimate of the incidence of major complications and to identify relevant risk factors.

Two mathematical models for predicting dispersion of particles in the human lung.

The dispersion of particles in the human lung is modeled as a series of virtual mixing tanks. Using the experimental results of Scherer et al. (1975, J. Appl. Physiol., 38(4), pp. 719-723) for a five-generation glass lung model, it is shown that each generation of the glass lung behaves like an independent virtual mixing tank. The corresponding resident time distribution is shown to have a variance approximately equal to the square of the average time a particle spends in the generation. By assuming that each generation of the human lung behaves as an independent virtual mixing tank, the realistic lung data provided by Weibel (1963, Morphometry of the Human Lung, Spinger-Verlag, New York) are used to validate this assumption in two ways. First, the half-width of the exhaled particle concentration profile is obtained. Second, a system of differential equations, with the concentration of particles in each mixing tank as its solution, is derived and solved numerically. This gives the exhaled concentration profile. Both techniques yield similar results to each other, and both give excellent agreement with the experimental data. The virtual mixing tank approach allows the complex mixing that occurs in the branching pathways of the lung to be more simply modeled. The model, thereby derived, is simple to change and could lead to enhancements in the understanding of the underlying processes contributing to the ventilation of the lung in health and disease.

Mothers' mental distress and parenting practices with infants and toddlers.

The purpose of this study was to examine whether maternal mental distress affects parenting practices related to monitoring activities (i.e. daily routines, enrichment activities). The nationally representative sample consisted of 1638 mothers. Maternal mental distress was assessed by the 5-item Mental Health Index (MHI). Logistic regression models were conducted, controlling for covariates (e.g. marital status, education level, etc.). Approximately 14% of the women reported high levels of mental distress and 25% of the women failed to engage in enrichment activities or consistent daily routines with their children. There was a significant adverse relationship between mental distress and routines, with women who were mentally distressed being more likely to not engage in daily routines. There was no significant relationship between mental distress and enrichment activities. Race differentials were evident among these relationships. These findings highlight the prevalence of maternal mental distress and its deleterious effects on select parenting behaviors.

Stability of an epidural analgesic admixture containing epinephrine, fentanyl and bupivacaine.

The addition of epinephrine to solutions containing fentanyl and bupivacaine for epidural infusion has been shown to improve the quality of analgesia. However, this admixture is not available commercially in the United Kingdom. Moreover, stability data applicable to UK practice for this admixture are limited. This study investigated the stability of fentanyl 2 microg.ml(-1) plus bupivacaine 1 mg.ml(-1) in PVC bags with and without epinephrine 2 microg.ml(-1) over a period of 184 days both at room temperature and at 4 degrees C. All infusions were found to be stable over the study period (> 90% remaining) using stability-indicating High Performance Liquid Chromatography (HPLC) methods, with no changes in physical appearance or pH (range 4.5-4.2). The infusions were prepared using standard pharmaceutical products, so facilitating the batch preparation of epinephrine, fentanyl and bupivacaine epidural solutions by hospital pharmacy departments.

Prospective randomized controlled trial of acute normovolaemic haemodilution in major gastrointestinal surgery.

BACKGROUND: The efficacy of acute normovolaemic haemodilution (ANH) remains uncertain because of a lack of well-designed prospective randomized controlled trials. The aim of this study was to assess the effects of ANH on allogeneic transfusion, postoperative complications, and duration of stay. METHODS: Consecutive patients undergoing major gastrointestinal surgery were randomized to a planned 3-unit ANH, or no ANH. Both groups underwent identical management including adherence to a transfusion protocol after surgery. Outcome measures included the number of patients receiving allogeneic blood, complications, and duration of stay. RESULTS: 380 patients were screened of which 160 were included in the study, median age was 62 yr (range 23-90), 'ANH' n=78, 'no ANH' n=82. There was no significant difference between groups in the number of patients receiving allogeneic blood 22/78 (28%) vs 25/82 (30%), the total number of allogeneic units transfused (90 vs 93), complication rate, or duration of stay. Haemodilution significantly increased anaesthetic time, median 55 (range 15-90) vs 40 min (range 17-80) (P<0.001). Significantly fewer patients in the ANH group experienced oliguria in the immediate postoperative period 37/78 (47%) vs 55/82 (67%) (P=0.012). The most significant factors affecting transfusion were blood loss, starting haemoglobin, and age. When compared with ASA-matched historical controls, the introduction of a transfusion protocol reduced the transfusion rate in colorectal patients from 136/333 (41%) to 37/138 (27%), P=0.004. CONCLUSIONS: In this large pragmatic study, ANH did not affect allogeneic transfusion rate in major gastrointestinal surgery. Preoperative haemoglobin, blood loss, and transfusion protocol are the key factors influencing allogeneic transfusion.

Acute normovolaemic haemodilution in colorectal surgery.

AIMS: Blood transfusions are often given to surgical patients. This study was designed to assess whether acute normovolaemic haemodilution (ANH) reduces exposure to allogeneic blood, affects clinical outcome and hospital stay, and is feasible in colorectal surgery. METHODS: All ASA 1 and 11 patients undergoing colectomies performed between 1997 and 1999 were identified retrospectively from our colorectal cancer database to ascertain our current peri and postoperative transfusion practice. Twenty-six selected patients subsequently underwent ANH during colectomy surgery. The number of patients and units transfused were identified. RESULTS: One hundred and twenty-three of 317 (39%) patients identified from our colorectal cancer database were transfused a total of 328 units (median 2, range 1-7). Of the 26 patients undergoing ANH, 4 (15%) were transfused a total of 13 units (median 3, range 2-5). The reduction in number of patients transfused was statistically significant (P=0.017). ANH increased anaesthetic time by a median of 19 min. There were no complications associated with ANH and the median hospital stay was 9 days (range 6-13). CONCLUSIONS: In this pilot study of selected patients, ANH is a feasible and effective method of reducing allogeneic blood exposure in major colorectal surgery. A prospective randomised controlled trial is now urgently required.

Standardized colour coding for syringe drug labels: a national survey.

A standardised colour code for user-applied syringe labels for anaesthetic drugs exists in the USA, Australia, New Zealand and Canada. In the UK, there is none. Consequently, an assortment of colour codes for syringe labels is available in the UK. We conducted a postal survey of the 285 College Tutors of the Royal College of Anaesthetists to establish their local syringe drug labelling system and their views on a national, standardised colour code. We found that that 96% of departments currently use coloured syringe drug labels. Of these, 98% use the 'Medilabel' scheme. The College Tutors felt that a standardised colour code for labels is required (94%), that the Association of Anaesthetists or the Royal College of Anaesthetists should be involved in the choice of scheme (76%) and that the scheme chosen should be international (65%). There was a majority feeling that the opinions expressed were representative of other members of the College Tutors' departments. We conclude that a national standard for drug labels is required and that a choice will have to be made between the 'international' scheme and the currently dominant Medilabel scheme.

A collaborative approach to the implementation of clinical supervision.

AIM: This paper discusses a collaborative approach to implementing clinical supervision, which was initiated between a primary care trust and a school of nursing and midwifery. BACKGROUND: To enable clinical supervision to proceed successfully and to be perceived as beneficial, this necessitates a collaborative partnership between clinicians, managers and educationalists. KEY ISSUES: The different stages of the initiative will be explored and the paper will consider examples of the collaborative processes involved. The evaluation of the project is examined and suggestions for the future continuation of the initiative are discussed. CONCLUSION: There is evidence that this has been a successful initiative and that a collaborative way of working can be beneficial when implementing clinical supervision.

Antibodies to glutamic acid decarboxylase and peripheral nerve function in type 1 diabetes.

Autoimmune mechanisms have been implicated in the pathophysiology of diabetic neuropathy. We studied the association between glutamic acid decarboxylase (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies to the autonomic nervous system and peripheral nerve function in recent onset type 1 diabetes. Thirty-seven patients (27 females and 10 males) enrolled 2-22 months after diagnosis. Humoral factors, glycemic control, and peripheral nerve function were measured annually for 3 yr. Patients with high GAD65Ab had worse glycemic control and higher insulin requirements. Patients with high GAD65Ab had slower motor nerve conduction velocities in the median, ulnar, and peroneal nerves (P < 0.025 for each nerve). The mean motor nerve conduction velocity Z scores at the time of the third evaluation was 0.341 +/- 0.25 for the low GAD65Ab patients and -0.600 +/- 0.25 for the high GAD65Ab patients (P < 0.01). Similar differences between the low and high GAD65Ab groups were observed for F wave latencies, thermal threshold detection, and cardiovascular autonomic function. The composite peripheral nerve function Z scores in the low GAD65Ab patients were 0.62 +/- 11, 0.71 +/- 0.19, and 0.21 +/- 0.14 at the first, second, and third evaluations, significantly different from those in the high GAD65Ab patients in whom they were -0.35 +/- 0.15, -0.46 +/- 0.18, and -0.42 +/- 0.16 (P < 0.001). In summary, GAD65Ab in patients with recent onset type 1 diabetes are associated with worse glycemic control and slightly worse peripheral nerve function. Although the latter remained within normal limits and none of the patients had clinical neuropathy, the GAD65Ab-related differences in composite peripheral nerve function were highly significant (P < 0.001) and could not be attributed to GAD65Ab-related differences in glycemic control.

Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland.

Although a link between primary cutaneous B-cell lymphoma (PCBCL) and Borrelia burgdorferi infection has long been suspected, previous studies have not demonstrated a significant association. The authors looked for evidence of B. burgdorferi in 20 cases of PCBCL from the Scottish Highlands, an area with endemic Lyme disease, and compared their findings with those in 40 control patients (20 undergoing wide reexcision at sites of malignant melanoma and 20 biopsies of inflammatory dermatoses). All studies were performed on formalin-fixed, paraffin-embedded tissues. The cases of PCBCL were classified according to criteria described by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group using a combination of morphology, immunohistochemistry, and seminested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement. A nested PCR was performed on deoxyribonucleic acid (DNA) extracts from the lymphoma and control cases using primers to a unique conserved region of the B. burgdorferi flagellin gene. B. burgdorferi-specific DNA was detected in seven of 20 lymphoma cases (five of 12 marginal zone lymphomas, one of five primary cutaneous follicle center cell lymphomas, one of three diffuse, large B-cell lymphomas of the leg) and in one melanoma reexcision patient of 40 control subjects. The relationship between B. burgdorferi and PCBCL was significant when compared with the control groups separately (p <0.05) or in combination (p <0.01). These results provide strong evidence to support the concept of B. burgdorferi-driven lymphomagenesis in the skin.

Decreased prorenin processing develops before autonomic dysfunction in type 1 diabetes.

It is well documented that diabetic patients with chronic complications have decreased renin secretion and elevations in the renin precursor prorenin. It is uncertain, however, whether the abnormal processing of prorenin is reflective of microvascular disease, hypertension, or autonomic neuropathy. Dechaux et al. (Transplant Proc. 18:1598-1599, 1986) observed abnormalities in prorenin processing in uncomplicated diabetes and suggested that it was the result of subclinical autonomic neuropathy. To test this hypothesis, we measured renin, prorenin, and autonomic function in early type 1 diabetes at a time when there is little or no microvascular disease or hypervolemia. Thirty-seven patients (10 males, 27 females) enrolled 2-22 months after diagnosis in a longitudinal study in which renin, prorenin, and autonomic function were measured annually for 3 years. Forty-one age-matched control subjects were also studied. PRA in the diabetic patients at the time of the second and third evaluations was 1.71 +/- 0.24 ng angiotensin I/mL x h and 1.67 +/- 0.24 ng angiotensin I/mL x h, respectively, significantly lower (P < 0.05) than that of the control subjects in whom PRA was 2.96 +/- 0.38 ng angiotensin I/mL x h. Prorenin was not different in the diabetic patients in comparison with controls. The renin to prorenin ratio in the diabetic patients at the time of the first, second, and third evaluations was 0.260 +/- 0.03, 0.235 +/- 0.05, and 0.227 0.05, respectively, significantly lower (P < 0.01) than in control subjects in whom the renin to prorenin ratio was 0.475 +/- 0.08. Despite this, at the time of the first and second evaluations, there was no evidence of autonomic dysfunction and no correlation between any test of autonomic function and the renin to prorenin ratio. At the time of the third evaluation, however, the intermediate frequency (0.04-0.15 Hz) power spectra while patients were supine (an index of sympathetic modulation of heart rate variability) showed a highly significant (P < .001) correlation with the renin to prorenin ratio. High frequency (0.15-0.40 Hz) spectra from supine patients at the third evaluation also correlated with the renin to prorenin ratio (P < 0.01). We conclude abnormal processing of prorenin develops in diabetic patients prior to microvascular disease, even before the first evidence of autonomic dysfunction. Although the latter may play a contributory role, additional as yet unidentified mechanisms seem to interrupt the processing of prorenin in early diabetes.