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Purpose: The SALUS study aims to improve the healthcare situation for glaucoma patients in Germany. In order to detect diurnal intraocular pressure (IOP) fluctuations, inpatient monitoring of IOP in an eye hospital for a minimum of 24 h is the current standard. SALUS assesses the benefits of a new form of outpatient care, where IOP can be measured by the patients themselves at home using a self-tonometer. This approach should promote the patient's health competence and empowerment within the healthcare system while reducing treatment costs. Methods: The SALUS study is a randomized controlled, open non-inferiority trial, alongside an economic analysis, determining whether outpatient monitoring of IOP with self-tonometry is at least as effective as current standard care and would reduce treatment costs. Participants (n = 1980) will be recruited by local ophthalmologists in the area of Westphalia-Lippe, Germany, and randomized to receive 7-day outpatient or 24-h inpatient monitoring. Participants in both study arms will also receive 24-h blood pressure monitoring. Furthermore, patient data from both study groups will be collected in an electronic case file (ECF), accessible to practitioners, hospitals, and the study participants. The primary endpoint is the percentage of patients with IOP peaks, defined as levels 30% above the patient-specific target pressure. Data will also be collected during initial and final examinations, and at 3, 6, and 9 months after the initial examination. Results: The study implementation and trial management are represented below. Conclusion: SALUS is a pioneering prospective clinical trial focused on the care of glaucoma patients in Germany. If SALUS is successful, it could improve the healthcare situation and health literacy of the patients through the introduction of various telemedical components. Furthermore, the approach would almost certainly reduce the treatment costs of glaucoma care. Trial registration: ClinicalTrials.gov ID: NCT04698876, registration date: 11/25/2020. DRKS-ID: DRKS00023676, registration date: 11/26/2020. [ABSTRACT FROM AUTHOR]

Background/Aims: The effects of a 10% α-hydroxy acid (AHA) oil/water (O/W) emulsion on the pH of human skin surface (pHss) and stratum corneum (SC; pHsc) were evaluated in vivo. Methods: The AHA O/W emulsion was applied to an area on the volar forearm of male volunteers (n = 12), and then wiped off after 10 min. Prior to application and over the following 3 h, the pHss was measured. We used glass electrode measurements and time domain dual lifetime referencing (tdDLR) with luminescent sensor foils. In another experiment (n = 5), the impact of the AHA O/W emulsion on the pHsc gradient was measured by tape stripping of the SC of the volar forearm after application of the AHA O/W emulsion. Results: Compared with pHss values prior to treatment [5.2 ± 1.7 (tdDLR) or 4.8 ± 0.5 (electrode)], the pHss was significantly reduced 10 min after application [4.0 ± 0.3 (tdDLR) or 4.1 ± 0.1 (electrode)] and the pHss remained significantly reduced over the measurement period of 3 h [after 3 h: 4.4 ± 0.2 (tdDLR) or 4.5 ± 0.3 (electrode)]. The AHA O/W emulsion significantly reduced the pHsc even down to deep layers of the SC. Conclusion: After a 10-min application time, the 10% AHA O/W emulsion reduces the pHss (for at least 3 h) and pHsc in deep layers of the SC. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BACKGROUND: Benign biliary strictures (BBS) are usually managed with plastic stents, whereas placement of uncovered metallic stents has been associated with failure related to mucosal hyperplasia. OBJECTIVE: We analyzed the efficacy and safety of temporary placement of a covered self-expanding metal stent (CSEMS) in BBS. DESIGN: Patients with BBS received temporary placement of CSEMSs until adequate drainage was achieved; confirmed by resolution of symptoms, normalization of liver function tests, and imaging. SETTING: Tertiary-care center with long-standing experience with CSEMSs. PATIENTS: Seventy-nine patients with BBS secondary to chronic pancreatitis (32), calculi (24), liver transplant (16), postoperative biliary repair (3), autoimmune pancreatitis (3), and primary sclerosing cholangitis (1). INTERVENTION: ERCP with temporary CSEMS placement. Removal of CSEMSs was performed with a snare or a rat-tooth forceps. MAIN OUTCOME MEASUREMENTS: End points were efficacy, morbidity, and clinical response. RESULTS: CSEMSs were removed from 65 patients. Resolution of the BBS was confirmed in 59 of 65 patients (90%) after a median follow-up of 12 months after removal (range 3-26 months). If patients who were lost to follow-up, developed cancer, or expired were considered failures, then an intent-to-treat global success rate of 59 of 79 (75%) was obtained. Complications associated with placement included 3 post-ERCP pancreatitis (4%), 1 postsphincterotomy bleed (1%), and 2 pain that required CSEMS removal (2%). In 11 patients (14%), the CSEMS migrated. In 1 patient, CSEMS removal was complicated by a bile leak that was successfully managed with plastic stents. LIMITATION: Pilot study from a single center. CONCLUSIONS: Temporary CSEMS placement in patients with BBS offers a potential alternative to surgery. [ABSTRACT FROM AUTHOR]

Introduction: Maternal deaths increased in the United States during 2018-2021, with documented racial disparities. Respectful maternity care is a component of quality care that includes preventing harm and mistreatment, engaging in effective communication, and providing care equitably. Improving respectful maternity care can be part of multilevel strategies to reduce pregnancy-related deaths., Methods: CDC analyzed data from the PN View Moms survey administered during April 24-30, 2023, to examine the following components of respectful care: 1) experiences of mistreatment (e.g., violations of physical privacy, ignoring requests for help, or verbal abuse), 2) discrimination (e.g., because of race, ethnicity or skin color; age; or weight), and 3) reasons for holding back from communicating questions or concerns during maternity (pregnancy or delivery) care., Results: Among U.S. mothers with children aged <18 years, 20% reported mistreatment while receiving maternity care for their youngest child. Approximately 30% of Black, Hispanic, and multiracial respondents and approximately 30% of respondents with public insurance or no insurance reported mistreatment. Discrimination during the delivery of maternity care was reported by 29% of respondents. Approximately 40% of Black, Hispanic, and multiracial respondents reported discrimination, and approximately 45% percent of all respondents reported holding back from asking questions or discussing concerns with their provider., Conclusions and Implications for Public Health Practice: Approximately one in five women reported mistreatment during maternity care. Implementing quality improvement initiatives and provider training to encourage a culture of respectful maternity care, encouraging patients to ask questions and share concerns, and working with communities are strategies to improve respectful maternity care., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Medicare cancer expenditures in the last month of life have increased. Aggressive cancer care at the end-of-life (ACEOL) is considered poor quality care. We used Geisinger Health Plan (GHP) last month's costs for cancer patients who died in 2018 and 2019 to determine the costs of and influence of Palliative Care (PC) on ACEOL., Method: Patients with GHP ages 18-99 who died in 2018 and 2019 were included. Demographic, clinical characteristics, and Charlson Comorbid Index were compared across care groups defined as no ACEOL indicator, 1 or more than 1 indicator. Differences between groups were compared with Kruskal-Wallis tests and one-way ANOVA for 3 groups. Median two-sample tests and independent t-tests compared groups of 2. A P-value 1. There were incremental cost increases with each additional ACEOL indicator (p = < .0001). Palliative Care <90 days before death was associated with increased costs while consultations >90 days before death lowered cost (P < .0001) due to reduced chemotherapy in the last month. Completed ADs reduced cost by $4000., Discussion: ACEOL indicators multiply costs during the last month of life. Palliative care instituted >90 days before death reduces chemotherapy in the last month of life and AD reduces health care costs., Conclusion: Cancer health care costs increase with indicators of ACEOL. Palliative care consultations >90 days before death; ADs reduce cancer health care costs.

More than 700 women die each year in the United States from complications related to pregnancy, and considerable racial and ethnic disparities continue to exist. Recognizing the urgent maternal warning signs of pregnancy-related complications, getting an accurate and timely diagnosis and quality care can save lives. In August 2020, the Centers for Disease Control and Prevention, Division of Reproductive Health launched a national communication campaign called "Hear Her" to raise awareness of urgent maternal warning signs during pregnancy and in the year after pregnancy and improve communication between pregnant or postpartum people and their support systems and health care providers. Storytelling is a central strategy to the campaign, which features video stories of women's experiences with pregnancy-related conditions to bring voices to the statistics and to help motivate action. These stories and additional campaign resources are disseminated through a website, digital media, organic (free) and paid social media, earned media, public service announcement distribution, and partners, with increased outreach to disproportionately affected communities. Partners in maternal and child health played an important role from campaign development to outreach and message dissemination. In the first year of the campaign, there were >390,000 unique visitors to the Hear Her website and 180 million impressions (number of times that content was displayed to a user) from digital and social media. Digital media allowed the campaign to reach priority audiences at a time when news and social media had a number of other urgent public health messages related to the COVID-19 pandemic.

Background: Early palliative care improves patient quality of life and influences cancer care. The time frame of early has not been established. Eight quality measures reflect aggressive care at the end of life. We retrospectively reviewed patients who died with cancer between January 1, 2018, through December 31, 2019, and compared the timing of palliative care consultation, advance directives (AD), and home palliative care with aggressive care at the end of life (ACEOL)., Methods: Patients without ACEOL indicators were compared to patients with one or more than one indicator of ACEOL. The proportion of patients who received palliative care, completed AD, and the timing of palliative care and AD (less than 30 days, 30-90 days, and greater than 90 days prior to death) was compared for patients who had ACEOL versus those who did not. Chi-square analysis was used for categorical data, one-way ANOVA for continuous variables, and odds ratio (OR) with confidence intervals (CI) was reported as a measure of effect size. A p value ≤ 0.05 was considered significant., Results: 1727 patients died, 46% were female, and the mean age was 69 (SD 11.91). Seventy-one percent had a palliative care consult, 26% completed AD, and 888 (51.4%) had at least one indicator of ACEOL. The most common indicator of ACEOL was new chemotherapy within 30 days of death, in 571 of 888 (64%) of patients experiencing ACEOL. ADs completed at any time reduced ACEOL (OR 0.80, 95%CI 0.64-0.99). Palliative care initiated at 30 days was associated with a greater risk of ACEOL (OR 5.32, 95% CI 3.94-7.18) and initiated between 30 and 90 days (OR 1.39, 95% CI 1.07-1.80) compared to no palliative care but was associated with reduced chemotherapy as an indicator of ACEOL when > 90 days (OR 0.46, 95% CI 0.38-0.57) before death., Discussion: Completed ADs were associated with reduced chemotherapy in the last 30 days of life and reduced ICU admissions. This may reflect goals of care and end-of-life discussions and transition of care to comfort measures. Palliative care paradoxically when initiated within 90 days before death was associated with greater ACEOL compared to no palliative care. This may be due to consultation late in the course of illness with a focus on crisis management in patients frequently utilizing the health care system. There is an associated reduction in the use of chemotherapy in the last 30 days of life if palliative care is consulted 90 days prior to death., Conclusions: An initial palliative care consult greater than 90 days before death and ADs completed at any time during the disease trajectory was associated only with reduced chemotherapy in the last 30 days of life compared with no palliative care among the 7 ACEOL indicators. ADs were associated with reduced ICU admissions. Most palliative care consults occurred within 90 days of death and a palliative care consult within 90 days of death is not an optimal utilization of services., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). Patients with concomitant PSC-IBD are at higher risk for IBD-related complications including dysplasia and malignancy, however the typical clinical IBD course is less severe. The aim of this study was to identify the prevalence of biologic use and therapeutic drug monitoring (TDM) in a cohort of PSC-IBD patients., Methods: Retrospective analysis of patients with PSC-IBD on biologic therapy who underwent TDM from Jan. 2018 to Aug. 2020 at the University of Virginia. Demographic data including age, disease duration, and comorbidities were recorded. IBD categorizations were recorded according to the Montreal Classification. Treatment outcomes including therapy changes after TDM were obtained., Results: A total of 157 patients with PSC-IBD were identified. Of these, 29 patients (19%) were treated with biologic therapy during the study period. 13 patients underwent reactive TDM due to primary or secondary loss of response and one patient underwent proactive TDM during the study period. Median duration of IBD in this group was 9 years, and the median duration of concomitant PSC-IBD was 5.8 years. 20 TDM tests were obtained in these 14 total patients. Sub-therapeutic drug levels were found in 12 tests among 8 patients, and 3 showed detectable anti-drug antibodies. 8 showed appropriate trough levels. TDM resulted in a change to IBD therapy (i.e., dose escalation, change in biologic therapy used, or addition of IBD medication) in 17 out of 20 tests., Conclusion: Herein we describe epidemiologic data of biologic use in PSC-IBD patients at an academic center. PSC-IBD classically follows a less severe clinical presentation and course. However, our study demonstrates that a subset of PSC-IBD patients exist which require biologic therapy and follow a more refractory clinical trajectory. In this subset, TDM showed a high incidence of sub-therapeutic trough levels and anti-drug antibodies, leading to a change in therapy in 85% of TDM instances. Larger studies are recommended to better understand this unique subset of PSC-IBD patients., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Pain perception is a subjective experience and is influenced by a variety of factors. Pain assessment tools, included the numeric pain rating scale (NRS) and the visual analog scale (VAS). A VAS qualitative (VASQ) scale asks patients their current pain level along a continuum of "Good Day," "Average Day," or "Bad Day." We had patients complete both scales and asked them their preference and reason for their choice., Methods: We identified patients 18 years of age and older, seen by Palliative medicine at Geisinger, who had cancer-associated pain of at least one-month duration. Patients filled out the study questionnaire composed of 2 questions. Characteristics of patients who preferred the VASQ were compared to those who preferred the NRS using a 2-sample t tests or Wilcoxon rank-sum tests and Pearson χ 2 or Fisher exact tests. The relationship between the NRS and the VASQ used the Pearson correlation coefficient., Results: One hundred forty-six patients completed the questionnaire, 52.1% were female; 63.7% preferred the NRS, 31.5% preferred the VASQ. Patients who preferred the NRS reported a higher NRS rating than patients who preferred the VASQ (mean NRS rating of 6.0 compared to 5.3) but the difference was not statistically significant ( P = .1531). Visual analog scale qualitative ratings were higher among patients who preferred the NRS, but the difference was not statistically different (mean rating of 5.2 vs 4.8, P = .3669)., Conclusion: Patients preferred the NRS over VASQ for pain assessment. Patients tend to rate their pain at a higher level when using NRS compared to VASQ.

Background and Aims: Intestinal biopsy sampling during IBD trials represents a valuable adjunct strategy for understanding drug responses at the tissue level. Given the length and distinctive embryonic origins of the proximal and distal colon, we investigated whether inherent regional differences of immune cell composition could introduce confounders when sampling different disease stages, or pre/post drug administration. Here, we capitalise on novel mass cytometry technology to perform deep immunophenotyping of distinct healthy colonic segments, using the limited numbers of biopsies that can be harvested from patients., Methods: Biopsies [2.8 mm] were collected from the caecum, transverse colon, descending colon, and rectum of normal volunteers. Intestinal leukocytes were isolated, stained with a panel of 37 antibodies, and mass cytometry data acquired., Results: Site-specific patterns of leukocyte localisation were observed. The proximal colon featured increased CD8+ T cells [particularly resident memory], monocytes, and CD19+ B cells. Conversely, the distal colon and rectum tissues exhibited enrichment for CD4+ T cells and antibody-secreting cells. The transverse colon displayed increased abundance of both γδ T cells and NK cells. Subsets of leukocyte lineages also displayed gradients of expression along the colon length., Conclusions: Our results show an inherent regional immune cell variation within colonic segments, indicating that regional mucosal signatures must be considered when assessing disease stages or the prospective effects of trial drugs on leukocyte subsets. Precise protocols for intestinal sampling must be implemented to allow for the proper interpretation of potential differences observed within leukocyte lineages present in the colonic lamina propria., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fentanyl has been FDA approval as an analgesic since 1968 and multiple different fentanyl preparations have been developed over the years. Little was known about it is clinical utility defined by risks and benefits until recently. Present commercially available preparations are easily tampered and nonpharmacologic fentanyl has become the major cause of opioid deaths in the United States. This state-ofthe-art review will discuss fentanyl pharmacology, utility, safety and abuse.

Background: Isokinetic testing of the trunk is ubiquitous in the literature and with training, however, there is a lack of normative data for adolescents and adult athletes., Purpose: The purpose of the current review is to present and summarize data about isokinetic trunk strength assessment relative to young, adolescent and adult athletes. Testing position variations, reliability values by age groups, utilization of strength measures and normative data by age groups have been discussed. The information presented within this review are of practical importance for assessment of isokinetic trunk strength to appraise the athlete's current strength level and provide suitable conditioning training program., Study Design: Literature review., Methods: NCBI-PubMed, Web of Science, and SPORTDiscus were searched to identify relevant correlation and intervention studies/trials related to isokinetic testing of the trunk. Forty-two studies meeting the inclusion criteria were included in this literature review., Evidence Synthesis: The validity of isokinetic trunk measures (i.e. peak torque; flexion/extension ratios) can be affected by a number of factors including whether the individual is tested in seated or standing position, which can alter the muscle length-tension relationship. Reliability is excellent for some strength measures and moderate to high for muscle endurance. Extension and concentric measures tend to have better reliability than flexion and eccentric measures respectively, while females show typically higher reliability scores than men due to the difficulty in controlling men's body position when testing. Normative data for various populations are provided., Conclusions: Muscle assessment methods using an isokinetic dynamometer are considered reliable with high correlations to peak strength values and flexor/extensor ratios over age groups. However, caution should be exercised when interpreting position-specific isokinetic test results that measure trunk flexion (standing vs seated position). Still, there are indications that low-velocity movements are more reliable for measuring trunk strength. In adolescence, boys appear stronger than girls, with higher values for trunk extensors. Trunk flexors and extensors ratios decrease with growth. Data of isokinetic trunk muscle performance seems to be correlated not only to anthropometric parameters but also to sports discipline and training volume. The effects of sport on the muscular strength of the trunk may have both a preventive factor and a possible risk factor for low back pain. There is evidence for an association between high physical workloads and back injury., Level of Evidence: 5., (© 2020 by the Sports Physical Therapy Section.)

Context: Patient's rating of perceived effort (RPE) is used to assess central fatigue. Cancer-related fatigue (CRF) is believed to be of central origin. The increased RPE with a motor task, such as the Finger-Tapping Test (FTT), can easily be measured in the clinical setting., Objectives: To correlate the FTT, RPE and the Brief Fatigue Inventory (BFI) rated fatigue severity in patients with cancer., Methods: Subjective fatigue was assessed in adult patients with cancer by the BFI. Participants performed a modified FTT with the index finger of the dominant hand: 15 seconds × 2, 30 seconds × 2, and 60 seconds × 2 with 1 minute of rest between each time trial. Rating of perceived effort at the end of task was measured by the Borg 10 scale., Exclusions: Brain metastasis, history of brain radiation, Parkinson disease, Huntington Chorea, multiple sclerosis, delirium, and depression. Pearson correlation coefficients were used to describe the relationships between BFI, FTT, and Borg 10 scale., Results: Thirty patients participated. Mean age was 56.2. Sixteen were females (53.3%). The mean BFI mean was 4.1, median 4.4. Tapping rate did not correlate with fatigue severity. The RPE correlated with the mean BFI: r s 0.438, P = .0155. These correlations persisted after adjustment for age., Conclusion: An increased RPE in the absence of task failure suggests that the origin of CRF is central. The performance of an FTT with RPE helps to improve our understanding of fatigue in the clinical setting.

Palmitoylethanolamide (PEA) is a nutraceutical endocannabinoid that was retrospectively discovered in egg yolks. Feeding poor children with known streptococcal infections prevented rheumatic fever. Subsequently, it was found to alter the course of influenza. Unfortunately, there is little known about its pharmacokinetics. Palmitoylethanolamide targets nonclassical cannabinoid receptors rather than CB1 and CB2 receptors. Palmitoylethanolamide will only indirectly activate classical cannabinoid receptors by an entourage effect. There are a significant number of prospective and randomized trials demonstrating the pain-relieving effects of PEA. There is lesser evidence of benefit in patients with nonpain symptoms related to depression, Parkinson disease, strokes, and autism. There are no reported drug-drug interactions and very few reported adverse effects from PEA. Further research is needed to define the palliative benefits to PEA.

Ginseng has been used for centuries to treat various diseases and has been commercially developed and cultivated in the past 300 years. Ginseng products may be fresh, dried (white), or dried and steamed (red). Extracts may be made using water or alcohol. There are over 50 different ginsenosides identified by chromatography. We did an informal systematic qualitative review that centered on fatigue, cancer, dementia, respiratory diseases, and heart failure, and we review 113 studies in 6 tables. There are multiple potential benefits to ginseng in cancer. Ginseng, in certain circumstances, has been shown to improve dementia, chronic obstructive pulmonary disease, and heart failure through randomized trials. Most trials had biases or unknown biases and so most evidence is of low quality. We review the gaps in the evidence and make some recommendations regarding future studies.

Parenteral potent opioid availability is becoming an issue in acute pain management. Two opioids, nalbuphine and buprenorphine, are available which can be substituted for hydromorphone, fentanyl, and morphine. There are advantages and disadvantages in using these 2 opioids which are discussed, and potential dosing strategies are outlined.

The buprenorphine receptor binding profile is unique in that it binds to all three major opioid receptors (mu, kappa, delta), and also binds to the orphan-like receptor, the receptor for orphanin FQ/nociceptin, with lower affinity. Within the mu receptor group, buprenorphine analgesia in rodents is dependent on the recently discovered arylepoxamide receptor target in brain, which involves a truncated 6-transmembrane mu receptor gene protein, distinguishing itself from morphine and most other mu opioids. Although originally designed as an analgesic, buprenorphine has mainly been used for opioid maintenance therapy and only now is increasingly recognized as an effective analgesic with an improved therapeutic index relative to certain potent opioids. Albeit a second-, third-, or fourth-line analgesic, buprenorphine is a reasonable choice in certain clinical situations. Transdermal patches and buccal film formulations are now commercially available as analgesics. This review discusses buprenorphine pharmacodynamics and pharmacokinetics, use in certain populations, and provides a synopsis of systematic reviews and randomized analgesic trials. We briefly discuss postoperative management in patients receiving buprenorphine maintenance therapy, opioid equivalence to buprenorphine, rotations to buprenorphine from other opioids, and clinical relevance of buprenorphine-related QTc interval changes.

Opioids adversely influence respiration in five distinct ways. Opioids reduce the respiratory rate, tidal volume, amplitude, reflex responses to hypercapnia and hypoxia, and arousability related necessary for respiratory adaptive responses. Opioids cause impairment of upper pharyngeal dilator muscles leading to obstructive apnea. Opioids cause complex sleep disordered breathing (SDB) consisting of central sleep apnea and obstructive sleep apnea. Clinically opioids worsen pre-existing SDB. Recent studies have shown increased morbidity and mortality in patients receiving opioids for chronic noncancer pain and chronic obstructive pulmonary disease, which appear to be related to cardiovascular events, not overdose. Both patient populations are at risk for sleep disordered breathing and increased risk for adverse cardiovascular events on opioids for dyspnea or pain. This review discusses the influence of opioids on respiration and SDB and will review the adverse respiratory and cardiovascular effects of opioid use in at risk populations. Recommendations regarding management will follow as a summary.

Introduction: Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma., Methods: Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days. Animals were assessed for survival, tumour size and spread, and tumour and immune related histological markers after 120 days. Peripheral blood mononuclear cells were tested for tumour-specific T cell activation and cytotoxicity. Immune modulatory cytokines tumour necrosis factor α, interleukin (IL)-2/IL-8/IL-10/IL-12 and interferon γ, and vascular endothelial growth factor were measured in serum., Results: Mean survival of untreated animals was 36 days, as compared with 97, 78 and 114 days for RFA, CpG and combination therapy, respectively. Compared with untreated controls, antitumour T cell stimulation/cytotoxicity increased 26/16-fold, 32/17-fold and 50/38-fold 2 weeks after RFA, CpG and combination treatments, respectively. The combination inhibited tumour spread to lungs and peritoneum significantly and prohibited new tumour growth in animals receiving a secondary systemic tumour cell injection. RFA alone induced a Th1 cytokine pattern, while IL-8 and IL-10 were only upregulated in CpG treated animals and controls., Conclusions: The combination of TLR9 stimulation with RFA resulted in a potentiated antitumour T cell response and cytotoxicity in the VX2 tumour model. Only this combination prevented subsequent tumour spread and resulted in a significantly improved survival, justifying the need for further exploration of the combination of ablative therapies and TLR9 agonists in liver cancer., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The skin pH is crucial for physiological skin functions. A decline in stratum corneum acidity, as observed in aged or diseased skin, may negatively affect physiological skin functions. Therefore, glycolic acid-containing water-in-oil (W/O) emulsions adjusted to pH 4 were investigated regarding their effect on normal or increased skin pH. A pH 4 W/O emulsion was applied on three areas with pathologically increased skin surface pH in diabetics (n = 10). Further, a 28-day half-side trial (n = 30) was performed to test the long-term efficacy and safety of a pH 4 W/O emulsion (n = 30). In summary, the application of a pH 4 W/O emulsion reduced the skin pH in healthy, elderly and diabetic subjects, which may improve epidermal barrier functions., (© 2015 The Author(s) Published by S. Karger AG, Basel.)

Aim: To study the safety and effectiveness associated with accelerated infliximab infusion protocols in patients with inflammatory bowel disease (IBD)., Methods: Original protocols and infusion rates were developed for the administration of infliximab over 90-min and 60-min. Then the IBD patients on stable maintenance infliximab therapy were offered accelerated infusions. To be eligible for the study, patients needed a minimum of four prior infusions. An initial infusion of 90-min was given to each patient; those tolerating the accelerated infusion were transitioned to a 60-min infusion protocol at their next and all subsequent visits. Any patient having significant infusion reactions would be reverted to the standard 120-min protocol. A change in a patient's dose mandated a single 120-min infusion before accelerated infusions could be administered again., Results: The University of Virginia Medical Center's Institutional Review Board approved this study. Fifty IBD patients treated with infliximab 5 mg/kg, 7.5 mg/kg and 10 mg/kg were offered accelerated infusions. Forty-six patients consented to participate in the study. Nineteen (41.3%) were female, five (10.9%) were African American and nine (19.6%) had ulcerative colitis. The mean age was 42.6 years old. Patients under age 18 were excluded. Ten patients used immunosuppressive drugs concurrently out of which six were taking azathioprine, three were taking 6-mercaptopurine and one was taking methotrexate. One of the 46 study patients used corticosteroid therapy for his IBD. Seventeen of the patients used prophylactic medications prior to receiving infusions; six patients received corticosteroids as pre-medication. Four patients had a history of distant transfusion reactions to infliximab. These reactions included shortness of breath, chest tightness, flushing, pruritus and urticaria. These patients all took prophylactic medications before receiving infusions. 46 patients (27 males and 19 females) received a total of fifty 90-min infusions and ninety-three 60-min infusions. No infusion reactions were reported. There were no adverse events, including drug-related infections. None of the patients developed cancer of any type during the study timeframe. Total cost savings for administration of the both 90-min and 60-min accelerated infusions compared to standard 120-min infusions was estimated to be $53 632 ($116 965 vs $63 333, P = 0.001). One hundred and eighteen hours were saved in the administration of the accelerated infusions (17 160 min vs 10 080 min, P = 0.001). In the study population, overweight females [body mass index (BMI) > 25.00 kg/m(2)] were found to have statistically higher BMIs than overweight males (mean BMI 35.07 ± 2.66 kg/m(2) vs 30.08 ± 0.99 kg/m(2), P = 0.05), finding which is of significance since obesity was described as being one of the risk factors for Crohn's disease., Conclusion: We are the first US group to report substantial cost savings, increased safety and patient satisfaction associated with accelerated infliximab infusion.