Long-Term Efficacy and Safety of Superficial Radiation Therapy in Subjects With Nonmelanoma Skin Cancer: A Retrospective Registry Study

Background: Low-dose superficial radiation therapy (SRT) effectively treats nonmelanoma skin cancer (NMSC) without requiring invasive excision. SRT is especially safe and effective among the elderly who comprise most patients with basal cell and squamous cell carcinomas (BCCs and SCCs). Objective: To demonstrate the long-term safety and efficacy of SRT for treating NMSC with a new generation device. Methods: A retrospective chart review was performed at four clinical study sites. The study population included male and female patients (N=516) treated with SRT for NMSC (N=776) including BCCs (n=448) and SCCs (n=328) prior to January 2015 with long-term follow-up records. Results: The overall mean (SD) total treatment dosage was 4652.33 (366.34) cGy (range, 3636.6 to 5455 cGy) administered over a mean of 12.3 (1.85) sessions. The overall Kaplan-Meier survival probability estimate (95% CI) was 0.989 (0.980, 0.998) at 24 months, 0.989 (0.969, 1.000) at 60 months, and 0.989 (0.942, 1.000) at 85 months. There were six recurrences of BCCs (n=4) and SCCs (n=2). The most common adverse event was hypopigmentation. Limitations: Retrospective study design and some incomplete data. Conclusion: It is estimated that 98.9% of nonmelanoma skin cancers will not recur after 85 months following superficial radiation therapy. J Drugs Dermatol. 2020;19(2)163-168. doi:10.36849/JDD.2020.4647

Pope Francis and Perinatal Palliative Care: Advancing the Culture of Mercy.

For the last 25 years, the Popes of the Roman Catholic Church have been vocal proponents of palliative care in an effort to promote human dignity, decrease human suffering, and discourage euthanasia and suicide. They have supported efforts to expand the scope and provision of palliative care. Recently, Pope Francis has focused on the need to provide perinatal palliative care. He has emphasized the need to do so as an act of mercy, love, and solidarity. His approach builds on the main pastoral theme of his Papacy, the mercy of God. This article outlines the thought of Pope Francis on the mercy of God and how he wishes to see this mercy motivate and invigorate not only the Church but all people. Perinatal palliative care becomes a further outgrowth of the love and mercy we show one another. It is a pastoral practice encouraged by the Church and consistent with Catholic doctrine and the mission of Catholic health-care facilities.

Cohort study of workers at a New Zealand agrochemical plant to assess the effect of dioxin exposure on mortality.

OBJECTIVES: To describe how the exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) influenced mortality in a cohort of workers who were exposed more recently, and at lower levels, than other cohorts of trichlorophenol process workers. DESIGN: A cohort study. SETTING: An agrochemical plant in New Zealand PARTICIPANTS: 1,599 men and women working between 1 January 1969 and 1 November 1988 at a plant producing the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) with TCDD as a contaminant. Cumulative TCDD exposure was estimated for each individual in the study by a toxicokinetic model. PRIMARY OUTCOME MEASURES: Calculation of cause-specific standardised mortality ratios (SMRs) and 95% confidence intervals (95% CI's) compared those never and ever exposed to TCDD. Dose-response trends were assessed firstly through SMRs stratified in quartiles of cumulative TCCD exposure, and secondly with a proportional hazards model. RESULTS: The model intercept of 5.1 ppt of TCDD was consistent with background TCDD concentrations in New Zealand among older members of the population. Exposed workers had non-significant increases in all-cancer deaths (SMR=1.08, 95% CI 0.86 to 1.34), non-Hodgkin lymphoma (SMR=1.57, 95% CI: 0.32 to 4.59), soft tissue sarcoma (one death) (SMR=2.38, 95% CI: 0.06 to 13.26), diabetes (SMR=1.27, 95% CI: 0.55 to 2.50) and ischaemic heart disease (SMR=1.21, 95% CI: 0.96 to 1.50). Lung cancer deaths (SMR=0.95, 95% CI: 0.56 to 1.53) were fewer than expected. Neither the stratified SMR nor the proportional hazard analysis showed a dose-response relationship. CONCLUSION: There was no evidence of an increase in risk for 'all cancers', any specific cancer and no systematic trend in cancer risk with TCDD exposure. This argues against the carcinogenicity of TCDD at lower levels of exposure.

Effect of electric stimulation on human chondrocytes and mesenchymal stem cells under normoxia and hypoxia.

During joint movement and mechanical loading, electric potentials occur within cartilage tissue guiding cell development and regeneration. Exposure of cartilage exogenous electric stimulation (ES) may imitate these endogenous electric fields and promote healing processes. Therefore, the present study investigated the influence of electric fields on human chondrocytes, mesenchymal stem cells and the co­culture of the two. Human chondrocytes isolated from articular cartilage obtained post­mortally and human mesenchymal stem cells derived from bone marrow (BM­MSCs) were seeded onto a collagen­based scaffold separately or as co­culture. Following incubation with the growth factors over 3 days, ES was performed using titanium electrodes applying an alternating electric field (700 mV, 1 kHz). Cells were exposed to an electric field over 7 days under either hypoxic or normoxic culture conditions. Following this, metabolic activity was investigated and synthesis rates of extracellular matrix proteins were analyzed. ES did not influence metabolic activity of chondrocytes or BM­MSCs. Gene expression analyses demonstrated that ES increased the expression of collagen type II mRNA and aggrecan mRNA in human chondrocytes under hypoxic culture conditions. Likewise, collagen type II synthesis was significantly increased following exposure to electric fields under hypoxia. BM­MSCs and the co­culture of chondrocytes and BM­MSCs revealed a similar though weaker response regarding the expression of cartilage matrix proteins. The electrode setup may be a valuable tool to investigate the influence of ES on human chondrocytes and BM­MSCs contributing to fundamental knowledge including future applications of ES in cartilage repair.

Shift Work and Cognitive Flexibility: Decomposing Task Performance.

Deficits in cognitive functioning associated with shift work are particularly relevant to occupational performance; however, few studies have examined how cognitive functioning is associated with specific components of shift work. This observational study examined how circadian phase, nocturnal sleepiness, and daytime insomnia in a sample of shift workers ( N = 30) were associated with cognitive flexibility during the night shift. Cognitive flexibility was measured using a computerized task-switching paradigm, which produces 2 indexes of flexibility: switch cost and set inhibition. Switch cost represents the additional cognitive effort required in switching to a different task and can impact performance when multitasking is involved. Set inhibition is the efficiency in returning to previously completed tasks and represents the degree of cognitive perseveration, which can lead to reduced accuracy. Circadian phase was measured via melatonin assays, nocturnal sleepiness was assessed using the Multiple Sleep Latency Test, and daytime insomnia was assessed using the Insomnia Severity Index. Results indicated that those with an earlier circadian phase, insomnia, and sleepiness exhibited reduced cognitive flexibility; however, specific components of cognitive flexibility were differentially associated with circadian phase, insomnia, and sleepiness. Individuals with an earlier circadian phase (thus more misaligned to the night shift) exhibited larger switch costs, which was also associated with reduced task efficiency. Shift workers with more daytime insomnia demonstrated difficulties with cognitive inhibition, whereas nocturnal sleepiness was associated with difficulties in reactivating previous tasks. Deficits in set inhibition were also related to reduced accuracy and increased perseverative errors. Together, this study indicates that task performance deficits in shift work are complex and are variably impacted by different mechanisms. Future research may examine phenotypic differences in shift work and the associated consequences. Results also suggest that fatigue risk management strategies may benefit from increased scope and specificity in assessment of sleep, sleepiness, and circadian rhythms in shift workers.

A Novel In Vitro System for Comparative Analyses of Bone Cells and Bacteria under Electrical Stimulation.

Electrical stimulation is a promising approach to enhance bone regeneration while having potential to inhibit bacterial growth. To investigate effects of alternating electric field stimulation on both human osteoblasts and bacteria, a novel in vitro system was designed. Electric field distribution was simulated numerically and proved by experimental validation. Cells were stimulated on Ti6Al4V electrodes and in short distance to electrodes. Bacterial growth was enumerated in supernatant and on the electrode surface and biofilm formation was quantified. Electrical stimulation modulated gene expression of osteoblastic differentiation markers in a voltage-dependent manner, resulting in significantly enhanced osteocalcin mRNA synthesis rate on electrodes after stimulation with 1.4VRMS. While collagen type I synthesis increased when stimulated with 0.2VRMS, it decreased after stimulation with 1.4VRMS. Only slight and infrequent influence on bacterial growth was observed following stimulations with 0.2VRMS and 1.4VRMS after 48 and 72 h, respectively. In summary this novel test system is applicable for extended in vitro studies concerning definition of appropriate stimulation parameters for bone cell growth and differentiation, bacterial growth suppression, and investigation of general effects of electrical stimulation.

Brain Cancer in Workers Employed at a Laboratory Research Facility.

BACKGROUND: An earlier study of research facility workers found more brain cancer deaths than expected, but no workplace exposures were implicated. METHODS: Adding four additional years of vital-status follow-up, we reassessed the risk of death from brain cancer in the same workforce, including 5,284 workers employed between 1963, when the facility opened, and 2007. We compared the work histories of the brain cancer decedents in relationship to when they died and their ages at death. RESULTS: As in most other studies of laboratory and research workers, we found low rates of total mortality, total cancers, accidents, suicides, and chronic conditions such as heart disease and diabetes. We found no new brain cancer deaths in the four years of additional follow-up. Our best estimate of the brain cancer standardized mortality ratio (SMR) was 1.32 (95% confidence interval [95% CI] 0.66-2.37), but the SMR might have been as high as 1.69. Deaths from benign brain tumors and other non-malignant diseases of the nervous system were at or below expected levels. CONCLUSION: With the addition of four more years of follow-up and in the absence of any new brain cancers, the updated estimate of the risk of brain cancer death is smaller than in the original study. There was no consistent pattern among the work histories of decedents that indicated a common causative exposure.

Hepatitis B vaccine immunogenicity among adults vaccinated during an outbreak response in an assisted living facility--Virginia, 2010.

BACKGROUND: Failure to adhere to infection control guidelines, especially during assisted monitoring of blood glucose, has caused multiple hepatitis B outbreaks in assisted living facilities (ALFs). In conjunction with the response to such an outbreak at an ALF ("Facility X") where most residents had neuropsychiatric disorders, we evaluated seroprotection rates conferred by hepatitis B vaccine and assessed the influence of demographic factors on vaccine response. METHODS: Residents were screened for hepatitis B and C infection, and those susceptible were vaccinated against hepatitis A and hepatitis B with one dose of TWINRIX™ (GSK) given at 0, 1, and 7 months. Blood samples were collected 1-2 months after receipt of the third vaccine dose to test for antibody to hepatitis B surface antigen (anti-HBs). RESULTS: Of the 27 residents who had post-vaccination blood specimens collected, 22 (81%) achieved anti-HBs concentrations ≥10 mIU/mL. Neither age nor neuropsychiatric comorbidity was a significant determinant of seroprotection. Geometric mean concentration was lower among residents aged 60-74 years (74.3 mIU/mL) than among residents aged 46-59 years (105.3 mIU/mL) but highest among residents aged ≥75 years (122.5 mIU/mL). The effect of diabetes on vaccination response could not be examined because 16/17 (94%) diabetic residents had HBV infection by the time of investigation. CONCLUSIONS: Adult vaccine recipients of all ages, even those over 60 years of age, demonstrated a robust capacity for achieving hepatitis B seroprotection in response to the combined hepatitis A/hepatitis B vaccine. The role for vaccination in interrupting HBV transmission during an outbreak remains unclear, but concerns about age-related response to hepatitis B vaccine may be insufficient to justify foregoing vaccination of susceptible residents of ALFs.

Semi-supervised adaptation in ssvep-based brain-computer interface using tri-training.

This paper presents a novel and computationally simple tri-training based semi-supervised steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI). It is implemented with autocorrelation-based features and a Naïve-Bayes classifier (NBC). The system uses nine characters presented on a 100 Hz CRT-monitor, three scalp electrodes for signal acquisition, a gUSB-amp for preamplification and two PCs for data-processing and stimulus control respectively. Preliminary test results of the system on nine healthy subjects, with and without tri-training, indicates that the accuracy improves as a result of tri-training.

Outbreak of hepatitis B virus infections associated with assisted monitoring of blood glucose in an assisted living facility-Virginia, 2010.

INTRODUCTION: In January 2010, the Virginia Department of Health received reports of 2 hepatitis B virus (HBV) infections (1 acute, 1 chronic) among residents of a single assisted living facility (ALF). Both infected residents had diabetes and received assisted monitoring of blood glucose (AMBG) at the facility. An investigation was initiated in response. OBJECTIVE: To determine the extent and mechanism of HBV transmission among ALF residents. DESIGN: Retrospective cohort study. SETTING: An ALF that primarily housed residents with neuropsychiatric disorders in 2 adjacent buildings in Virginia. PARTICIPANTS: Residents of the facility as of March 2010. MEASUREMENTS: HBV serologic testing, relevant medical history, and HBV genome sequences. Risk ratios (RR) and 95% confidence intervals (CIs) were used to identify risk factors for HBV infection. RESULTS: HBV serologic status was determined for 126 (91%) of 139 residents. Among 88 susceptible residents, 14 became acutely infected (attack rate, 16%), and 74 remained uninfected. Acute HBV infection developed among 12 (92%) of 13 residents who received AMBG, compared with 2 (3%) of 75 residents who did not (RR  = 35; 95% CI, 8.7, 137). Identified infection control breaches during AMBG included shared use of fingerstick devices for multiple residents. HBV genome sequencing demonstrated 2 building-specific phylogenetic infection clusters, each having 99.8-100% sequence identity. LIMITATIONS: Transfer of residents out of the facility prior to our investigation might have contributed to an underestimate of cases. Resident interviews provided insufficient information to fully assess behavioral risk factors for HBV infection. CONCLUSIONS: Failure to adhere to safe practices during AMBG resulted in a large HBV outbreak. Protection of a growing and vulnerable ALF population requires improved training of staff and routine facility licensing inspections that scrutinize infection control practices.

Epidemic cholera in a crowded urban environment, Port-au-Prince, Haiti.

We conducted a case-control study to investigate factors associated with epidemic cholera. Water treatment and handwashing may have been protective, highlighting the need for personal hygiene for cholera prevention in contaminated urban environments. We also found a diverse diet, a possible proxy for improved nutrition, was protective against cholera.

Reproducibility of BMD measurements in the prosthetic knee comparing knee-specific software to traditional DXA software: a clinical validation.

The aim of this study was to validate new knee-specific dual X-ray absorptiometry (DXA) software for cemented total knee arthroplasty (TKA) before initiation of a randomized controlled trial. Firstly, in a phantom study, we evaluated if cementation influenced the measured BMD (g/cm²), the scan reproducibility with the new knee-specific software, and the consequences of leg rotation around a vertical axis. Secondly, in a clinical study, we assessed the clinical reproducibility in repetitive scans performed with the new knee-specific software and with traditional spine-mode DXA software, and further compared the 2 softwares' ability to point type implant and bone edges correctly. Cementation increased the measured bone mineral density (BMD) (p < 0.01). For reproducibility, the coefficient of variation (CV) was 0.52-0.70% in vitro. Leg rotation around a vertical axis significantly changed the measured BMD in most scans. Automatic point typing of implant and bone edge was of varying quality with frequent need of manual correction for both softwares. CVs of clinical reproducibility ranged from 2.78% to 6.19% for knee-specific software and from 1.45% to 6.06% for spine-mode software. We found the new knee-specific software valid for BMD measurement of the bone in proximity of cemented TKA and with clinical reproducibility and corrections of point typing similar to traditional spine-mode software.

Dietary vitamin D intake and cancers of the colon and rectum: a case-control study in Italy.

Epidemiologic evidence indicates that vitamin D is inversely associated with risk of colon or rectal cancer or both. Using data from a case-control study conducted in Italy between 1992 and 1996, we examined the relation between dietary intake of vitamin D and colon and rectal cancer risk. The study population comprised patients with incident colon cancer (n = 1,225) or rectal cancer (n = 728) and 4,154 hospital controls. Odds ratios (OR) and 95% confidence intervals (CI) according to deciles of vitamin D intake were estimated by multiple logistic regression. In addition, we adjusted for intensity of sunlight exposure through stratification by geographic region of residence, and we computed ORs separately by anatomic subsite within the colon. Adjusted ORs for colon cancer were seen to decrease after the 5th decile of vitamin D intake and reached 0.69 (95% CI = 0.50-0.96) for the 9th and 10th deciles, reflecting a statistically significant inverse trend. The inverse association appeared to be somewhat more pronounced for the proximal than the distal colon and was similar among strata of geographic region and calcium intake. Rectal cancer was unrelated to vitamin D intake in this population. In conclusion, we observed an inverse association between dietary vitamin D intake and colon cancer risk among those with the highest intake levels, which was somewhat unexpected given that these levels were still substantially below the levels considered optimal for colon cancer prevention.

Methodologic issues in follow-up studies of cancer incidence among occupational groups in the United States.

PURPOSE: Incidence studies of occupational factors and cancer in the United States are problematic because the use of population-based registries to identify cases requires development of historical data on subjects' residences and often severely restricts the time period of follow up. This article describes procedures for addressing these challenges. METHODS: We used data from studies of cancer incidence and mortality among microelectronics industry employees to assess various methods for developing residential histories and the relative informativeness of the two studies. RESULTS: We developed residential histories for 98% of 99,229 mortality study subjects. Analyses making alternative assumptions about residential histories yielded standardized incidence ratios varying by at most 6%. Use of postemployment residential histories increased person-years by up to 62% and increased the observed number of cancers by up to 28%. The proportion of mortality study person-years included in the cancer incidence study ranged from 40% to 77% among work activity subcohorts. The number of observed cancer cases in the incidence study was 60% higher than the number of observed cancer deaths in the mortality study. CONCLUSIONS: Assumptions about residential history had little impact on validity. Use of information sources with national coverage to develop residential histories increased the incidence study's precision. Despite geographic and temporal restrictions, incidence studies provide more data than mortality studies on cancers with good survival. However, the potential for selection bias in incidence studies may vary considerably among subcohorts, indicating the need for cautious interpretation of such research.

Exposure assessment for retrospective follow-up studies of semiconductor- and storage device-manufacturing workers.

OBJECTIVE: This exposure assessment was conducted in the first large study of mortality and cancer incidence in semiconductor and storage device manufacturing. METHODS: Unique combinations of division, department and job codes and names (DDJ) from work history records were assigned to work groups and exposure categories. Agent exposure matrices assessed differences in potential exposures between groups. Changes in exposure over time were tracked by dividing the production history into manufacturing eras. RESULTS: Nineteen work groups were developed to capture 310,351 unique DDJs from 1965-1999. Agent exposure matrices contrasted exposure potential to solvents, metals, and work in cleanrooms between groups, and three manufacturing eras were identified for each site. CONCLUSIONS: The work groups, manufacturing eras and agent matrices have been used to classify workers in the study of cancer incidence and mortality.

Mortality among semiconductor and storage device-manufacturing workers.

PROBLEM: We evaluated mortality during 1965 to 1999 among 126,836 workers at two semiconductor facilities and one storage device facility. METHOD: We compared employees' cause-specific mortality rates with general population rates and examined mortality patterns by facility, duration of employment, time since first employment, and work activity. RESULTS: Employees had lower-than-expected mortality overall (6579 observed deaths, standardized mortality ratio [SMR] = 65; 95% confidence interval [CI] = 64-67), for all cancers combined (2159 observed, SMR = 78, 95% CI = 75-81) and for other major diseases. Central nervous system cancer was associated with process equipment maintenance at one of the semiconductor facilities (10 observed, SMR = 247, 95% CI = 118-454). Prostate cancer was associated with facilities/laboratories at the storage device facility (18 observed, SMR = 198, (5% CI = 117-313). CONCLUSIONS: Further evaluation of workplace exposures or independent investigations of similar occupational groups may clarify the interpretation of associations observed in this study.

Cutaneous manifestations of disease in athletes.

Various means of skin injury in athletes are examined, supplementing those discussed in Cutaneous Manifestations of Disease Part 1 (November/ December). Skin injury due to mechanical means such as corns, calluses, talon noir (calcaneal petechiae), tennis toe, joggers nipples, and piezogenic pedal papules will be discussed followed by a thorough discussion of environmental means of skin injury. There are a variety of ways that the environment may affect athletes both during competition and years after the competition is finished. The discussion will conclude with a look at performance-enhancing drugs and their effect on an athletes skin, and how the practitioner can better appreciate and perhaps prevent the long-term sequelae of drug abuse.

Association between brain tissue pH and brain injury during asphyxia in piglets.

BACKGROUND: Acidosis may contribute to brain injury from asphyxia, but its role is unclear. In order to evaluate the association between brain acidosis and cerebral injury, we subjected piglets to hypoxia and hypotension (HYP-HOTN) or hypoxia alone (HYP) to inflict varying amounts of brain damage. We hypothesized that piglets with a more severe brain injury would have a lower brain pH. METHODS: Piglets had a pH microprobe inserted into the cerebral cortex. HYP animals breathed 5-8% O(2)/7% CO(2) for 30 min with mean arterial pressure (MAP) maintained at >40 mmHg. HYP-HOTN animals breathed the same gas for 30 min, but during the last 15 min, MAP was reduced to 25-30 mmHg by withdrawing blood. After 4 h of recovery, the animals were perfusion-fixed and pathology assessed. Somatosensory-evoked potentials (SEP) were also monitored. RESULTS: HYP-HOTN piglets had more neuropathology than HYP animals. During the last 15 min of injury, brain pH in the HYP-HOTN group was significantly higher than that in HYP. However, recovery of brain pH was prolonged in the HYP-HOTN animals. The amount of time for brain pH to recover to > or =7.00 correlated very well with both the degree of neuropathology and SEP recovery. The reduction in brain pH, either absolute or relative to baseline, was not associated with the severity of damage. CONCLUSIONS: The time needed for brain pH to recover after asphyxia, but not its severity, was associated with the amount of brain injury. Further study is warranted to determine whether immediate restoration of brain pH will reduce brain damage.

Observer performance studies: detection of single versus multiple abnormalities of the chest.

OBJECTIVE: We used receiver operating characteristic (ROC) analysis to compare two methods of evaluating observer performance in detecting an abnormality on chest radiographs. In the first method, the abnormality in question, rib fracture, was one of five investigated, and it was the only one of interest in the second. MATERIALS AND METHODS: Eight experienced observers viewed 117 posteroanterior chest radiographs in two interpretation modes. Fifty-four of these images depicted rib fractures that had been rated as subtle for detection. The likelihood of the presence of a rib fracture was rated as one of five abnormalities in question in one mode and the sole abnormality of interest in the other mode. RESULTS: Six of the observers performed better during the single-abnormality mode, one performed equally well in both modes, and one performed better during the multiple-abnormality mode. The average area under the ROC curves (A(z)) was 0.73 +/- 0.07 for the multiple-abnormality mode and 0.80 +/- 0.04 for the single-abnormality mode. The results were significantly different (p < 0.05). CONCLUSION: Study methodology can significantly affect the results in ROC studies, particularly for abnormalities that may not be perceived as primary or important. The order in which abnormalities appear on a checklist report form may be important.