Lung cancer: a nationwide analysis of sex and age incidence trends from 1980 to 2022.

BACKGROUND: Lung cancer, once rare, has evolved into the global leading cause of cancer-related mortality, primarily driven by widespread cigarette smoking in the 20th century. This study explores the historical trends of lung cancer incidence in Denmark over four decades, emphasizing the impact of smoking prevalence, age, and gender on the observed patterns. MATERIALS AND METHODS: Drawing upon data from the Danish National Patient Register and information on smoking habits provided by the Danish Health Authority, this study investigates lung cancer incidence rates, demographic shifts, and smoking prevalence from 1980 to 2022. RESULTS: Smoking prevalence exhibited a consistent decline in males from 1950 to 2022, whereas female smoking prevalence maintained a stable level from 1950 to 1987, followed by a subsequent decline from 1987 to 2022. A peak in lung cancer crude incidence rates was identified during 2014-2017, with no significant difference observed before and after this period. Over the period, the gender distribution transitioned from a male majority to an equal male-female ratio, and age-specific disparities indicated declines in patients aged 50-59 and increases in those above 80 years. INTERPRETATION: The certainty of a decline in lung cancer incidence in the coming years remains unclear. Based on smoking prevalence, it might still be a decade away. To ensure a sustained decline in lung cancer incidence, targeted interventions are imperative, including customized smoking cessation programs that could be designed favorably for females. Given the modest decline in smoking prevalence over the last decade, legislation aimed at discouraging young individuals from smoking is pivotal. As of now, these efforts have not been implemented in Denmark.

Exploring the feasibility of bacteriocins EntK1 and EntEJ97s in treatment of systemic vancomycin resistant enterococci infections in mice.

AIMS: Enterocins K1 and EJ97 have specific antimicrobial activity against Enterococcus faecium and Enterococcus faecalis, respectively. The aim of this study was to investigate the utility of these enterocins for in vivo treatment of systemic enterococcal infections. METHODS AND RESULTS: The antimicrobial effect in blood was analysed and compared against the effect in saline. Colony forming unit counts revealed that the enterocins killed all the bacteria within 1 hour. Additionally, the bactericidal effect against E. faecalis was more rapid in blood, indicating a possible synergy between EntEJ97 and blood. Importantly, no enterocin resistant mutants emerged in these experiments. Injecting the enterocins intraperitoneally in an in vivo mouse model and using fluorescence and minimum inhibitory concentration determination to estimate concentrations of the peptides in plasma, indicate that the enterocins exist in circulation in therapeutic concentrations. Alanine aminotransferase detection, and haemolysis analysis indicates that there is no detectable liver damage or haemolytic effect after injection. CONCLUSIONS: The study revealed that EntK1 and EntEJ97 are able to kill all bacteria ex vivo in the presence of blood. In vivo experiments determine that the enterocins exist in circulation in therapeutic concentrations without causing liver damage or haemolysis. Future experiments should test these peptides for treatment of infection in a relevant in vivo model.

Learning effect of online versus onsite education in health and medical scholarship - protocol for a cluster randomized trial.

BACKGROUND: The disruption of health and medical education by the COVID-19 pandemic made educators question the effect of online setting on students' learning, motivation, self-efficacy and preference. In light of the health care staff shortage online scalable education seemed relevant. Reviews on the effect of online medical education called for high quality RCTs, which are increasingly relevant with rapid technological development and widespread adaption of online learning in universities. The objective of this trial is to compare standardized and feasible outcomes of an online and an onsite setting of a research course regarding the efficacy for PhD students within health and medical sciences: Primarily on learning of research methodology and secondly on preference, motivation, self-efficacy on short term and academic achievements on long term. Based on the authors experience with conducting courses during the pandemic, the hypothesis is that student preferred onsite setting is different to online setting. METHODS: Cluster randomized trial with two parallel groups. Two PhD research training courses at the University of Copenhagen are randomized to online (Zoom) or onsite (The Parker Institute, Denmark) setting. Enrolled students are invited to participate in the study. Primary outcome is short term learning. Secondary outcomes are short term preference, motivation, self-efficacy, and long-term academic achievements. Standardized, reproducible and feasible outcomes will be measured by tailor made multiple choice questionnaires, evaluation survey, frequently used Intrinsic Motivation Inventory, Single Item Self-Efficacy Question, and Google Scholar publication data. Sample size is calculated to 20 clusters and courses are randomized by a computer random number generator. Statistical analyses will be performed blinded by an external statistical expert. DISCUSSION: Primary outcome and secondary significant outcomes will be compared and contrasted with relevant literature. Limitations include geographical setting; bias include lack of blinding and strengths are robust assessment methods in a well-established conceptual framework. Generalizability to PhD education in other disciplines is high. Results of this study will both have implications for students and educators involved in research training courses in health and medical education and for the patients who ultimately benefits from this training. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov: NCT05736627. SPIRIT guidelines are followed.

Two novel prehabilitation apps to help patients stop smoking and risky drinking prior to hip and knee arthroplasty.

PURPOSE: Daily smoking or risky drinking increases the risk of complications after surgery by ~50%. Intensive prehabilitation aimed at complete cessation reduces the complication rate but is time-consuming. The purpose of this study was to carry out preoperative pilot tests (randomized design) of the feasibility (1A) and validation (1B) of two novel prehabilitation apps, habeat® (Ha-app) or rehaviour® (Re-app). METHODS: Patients scheduled for hip or knee arthroplasty with daily smoking, risky drinking, or both were randomised to one of the two apps. In part 1A, eight patients and their staff measured feasibility on a visual analog scale (VAS) and were interviewed about what worked well and the challenges requiring improvement. In part 1B, seven patients and their staff tested the improved apps for up to two weeks before validating the understanding, usability, coverage, and empowerment on a VAS and being interviewed. RESULTS: In 1A, all patients and staff returned scores of ≥5 for understanding the apps and mostly suggested technical improvements. In 1B, the scores varied widely for both apps, with no consensus achieved. Two of four patients (Ha-app) and one-third of the patients (Re-app) found the apps helpful for reducing smoking, but without successful quitting. The staff experienced low app competencies among patients and high time consumption. Specifically, patients most often needed help for the Ha-app, and the staff most often for Re-app; however, the staff reported the Re-app dashboard was more user-friendly. Support and follow-up from an addiction specialist staff member were suggested to complement the apps, thereby increasing the time consumption for staff. CONCLUSIONS: This pilot study to test prototype apps generated helpful feedback for the app developers. Based on the patient and staff comments, multiple improvements in functionality seem required before scaling up the evaluation for effect on prehabilitation and postoperative complications.

Minor effect of patient education for alcohol cessation intervention on outcomes after acute fracture surgery: a randomized trial of 70 patients.

BACKGROUND AND PURPOSE: High alcohol intake is associated with increased risk of postoperative complications. Alcohol cessation intervention is recommended prior to elective surgery. We investigated short- and long-term effects of perioperative intensive alcohol intervention in relation to acute ankle fracture surgery. PATIENTS AND METHODS: 70 patients requiring ankle fracture surgery and consuming ≥ 21 drinks weekly (1 drink = 12 g ethanol) were randomized to a manual-based 6-week intensive standardized alcohol cessation program, the Gold Standard Program (GSP-A), or treatment as usual (TAU), on the day of operation. GSP-A included 5 personal meetings, patient education, and motivational and pharmacological support (alcohol withdrawal prophylaxis, B vitamins, and low-dose disulfiram). Complications requiring treatment were measured after 6 weeks and 1 year. Alcohol intake was validated by biomarkers. Quality of life (QoL) was measured by the SF-36. Hospital costs were obtained from the National Hospital Costs Register. RESULTS: Postoperatively, complete alcohol cessation was higher in the GSP-A than in the TAU group (18/35 vs. 5/35, number needed to treat = 3, p ≤ 0.001), but not lowrisk consumption in the long term (10/35 vs. 7/33, p = 0.5). Number of complications in the short and long term (12/35 vs. 14/33, 16/35 vs. 18/33), the SF-36 score, or hospital costs in the short and long term (€6,294 vs. €8,024, €10,662 vs. €12,198), were similar between the groups. INTERPRETATION: Despite an effect on alcohol cessation and a positive tendency as regards the other outcomes, the postoperative complications, QoL, and costs were similar. Better perioperative strategies for acute surgical patients with high alcohol intake therefore need to be developed.

Characteristics of Patients in Treatment for Alcohol and Drug Addiction Who Succeed in Changing Smoking, Weight, and Physical Activity: A Secondary Analysis of an RCT on Combined Lifestyle Interventions.

INTRODUCTION: Patients addicted to alcohol or drug often have additional unhealthy lifestyles, adding to the high mortality and morbidity in this patient group. Therefore, it is important to consider lifestyle interventions as part of the usual addiction treatment. OBJECTIVE: The aim was to identify predictors of successful changes in lifestyle risk factors among patients in treatment for alcohol or drug addiction. METHODS: We conducted a secondary analysis of a trial using a 6-week intensive integrated lifestyle intervention: The very integrated program (VIP). Patients were recruited in Addiction Centres Malmö and Psychiatry Skåne, Sweden. The primary outcome was successful changes in lifestyle, measured as quitting tobacco, exercising 30 min per day, and not being over- or underweight after 6 weeks and 12 months. RESULTS: A total of 212 patients were included in the RCT, and 128 were included in this secondary analysis: 108 at 6 weeks and 89 at 12 months of follow-up. A total of 69 patients were respondents at both follow-ups. The follow-up rates were 51 and 42%, respectively. More education, having at least 2 lifestyle risk factors and having a high quality of life were predictors of a successful change in lifestyle after 6 weeks. After 12 months, the predictors for a successful outcome were having 3 or more risk factors, while an education level up to 3 years was a negative predictor. CONCLUSIONS: Having several unhealthy lifestyles in addition to alcohol and drug addiction was a significant predictor of successful lifestyle changes in the short- and long term after the VIP for lifestyle interventions. Likewise, education was significant. The results should be considered in future development and research among this vulnerable group of patients.

The Influence of Perioperative Fluid Therapy on N-terminal-pro-brain Natriuretic Peptide and the Association With Heart and Lung Complications in Patients Undergoing Colorectal Surgery: Secondary Results of a Clinical Randomized Assessor-blinded Multicenter Trial.

OBJECTIVE: To investigate the influence of intravenous (iv) fluid volumes on the secretion of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP) in colorectal surgical patients and its association with cardiopulmonary complications (CPC). In addition, to examine if preoperative NT-Pro-BNP can predict the risk for postoperative CPC. METHODS: Blood samples from patients enrolled in a previously published clinical randomized assessor-blinded multicenter trial were analyzed. Included were adult patients undergoing elective colorectal surgery with the American-Society-of-Anesthesiologists-scores of 1-3. Samples from 135 patients were available for analysis. Patients were allocated to either a restrictive (R-group) or a standard (S-group) iv-fluid regimen, commencing preoperatively and continuing until discharge. Blood was sampled every morning until the fourth postoperative day. The primary outcome for this study was NT-Pro-BNP changes and its association with fluid therapy and CPC. RESULTS: The S-group received more iv-fluid than the R-group on the day-of-surgery [milliliter, median (range) 6485 (4401-10750) vs 3730 (2250-8510); P < 0.001] and on the first postoperative day. NT-Pro-BNP was elevated in the S-group compared with the R-group on all postoperative days [area under the curve: median (interquartile range) pg/mL: 3285 (1697-6179) vs 1290 (758-3719); P < 0.001 and in patients developing CPC vs no-CPC (area under the curve), median (interquartile range): 5196 (1823-9061) vs 1934 (831-5301); P = 0.005]. NT-pro-BNP increased with increasing fluid volumes all days (P < 0.003). Preoperative NT-Pro-BNP predicted CPC [odds ratio (confidence interval): 1.573 (0.973-2.541), P = 0.032; positive predictive value = 0.257, negative predictive value = 0.929]. CONCLUSIONS: NT-pro-BNP increases with iv-fluid volumes given to colorectal surgical patients, and the level of NT-Pro-BNP is associated with CPC. Preoperative NT-Pro-BNP is predictive for CPC, but the diagnostic value is low.Clinicaltrials.gov NCT03537989.

Evaluation of Very Integrated Program: Health Promotion for Patients With Alcohol and Drug Addiction-A Randomized Trial.

BACKGROUND: Compared to the general population, patients with alcohol and drug addiction have an increased risk of additional hazardous lifestyles and suffer from more chronic diseases, adding to their already significantly higher morbidity and mortality. The objective of this study was to test the efficacy of the Very Integrated Program (VIP) on treatment and health outcomes for patients diagnosed with alcohol and drug addiction. METHODS: Parallel randomized clinical trial with intervention as add-on to addiction care as usual. A total of 322 patients aged 18 years or older were identified, and the study requirements were fulfilled by 219 patients, 7 of whom participated in a pilot. The intervention was a 6-week intensive, tailored, educational program that included motivational interviewing, a smoking cessation program, dietary and physical activity counseling, and patient education. The main outcome measures were substance-free days, time to relapse, and treatment adherence assessed after 6 weeks and 12 months. Secondary outcomes were lifestyle factors, symptoms of comorbidity, and quality of life. Missing data were imputed conservatively by using data closest to the follow-up date and baseline values in patients with no follow-up. RESULTS: The 212 patients (intervention, n = 113; control, n = 99) were randomized, and 202 had complete data for primary outcomes. After 6 weeks, there were no significant differences between the groups regarding primary or secondary outcomes. At the 12-month follow-up, the patients in the control group had significantly more total substance-free days (139 days; ranging 0 to 365 vs. 265; 0 to 366, p = 0.021)-specifically among the patients with drug addiction-and higher physical and mental quality of life (45 vs. 58, p = 0.049 and 54 vs. 66, p = 0.037), but not in the per-protocol analysis (60 vs. 46, p = 0.52 and 70 vs. 66, p = 0.74). The sensitivity analyses did not support significant differences between the groups. CONCLUSION: Overall, adding VIP intervention did not improve outcome of the alcohol or drug addiction care or the lifestyle compared to the addiction care alone. This patient group is still in need of effective programs, and new intervention research is required to develop that.

Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation.

Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.

Alternative Biosynthetic Starter Units Enhance the Structural Diversity of Cyanobacterial Lipopeptides.

Puwainaphycins (PUWs) and minutissamides (MINs) are structurally analogous cyclic lipopeptides possessing cytotoxic activity. Both types of compound exhibit high structural variability, particularly in the fatty acid (FA) moiety. Although a biosynthetic gene cluster responsible for synthesis of several PUW variants has been proposed in a cyanobacterial strain, the genetic background for MINs remains unexplored. Herein, we report PUW/MIN biosynthetic gene clusters and structural variants from six cyanobacterial strains. Comparison of biosynthetic gene clusters indicates a common origin of the PUW/MIN hybrid nonribosomal peptide synthetase and polyketide synthase. Surprisingly, the biosynthetic gene clusters encode two alternative biosynthetic starter modules, and analysis of structural variants suggests that initiation by each of the starter modules results in lipopeptides of differing lengths and FA substitutions. Among additional modifications of the FA chain, chlorination of minutissamide D was explained by the presence of a putative halogenase gene in the PUW/MIN gene cluster of Anabaena minutissima strain UTEX B 1613. We detected PUW variants bearing an acetyl substitution in Symplocastrum muelleri strain NIVA-CYA 644, consistent with an O-acetyltransferase gene in its biosynthetic gene cluster. The major lipopeptide variants did not exhibit any significant antibacterial activity, and only the PUW F variant was moderately active against yeast, consistent with previously published data suggesting that PUWs/MINs interact preferentially with eukaryotic plasma membranes.IMPORTANCE Herein, we deciphered the most important biosynthetic traits of a prominent group of bioactive lipopeptides. We reveal evidence for initiation of biosynthesis by two alternative starter units hardwired directly in the same gene cluster, eventually resulting in the production of a remarkable range of lipopeptide variants. We identified several unusual tailoring genes potentially involved in modifying the fatty acid chain. Careful characterization of these biosynthetic gene clusters and their diverse products could provide important insight into lipopeptide biosynthesis in prokaryotes. Some of the variants identified exhibit cytotoxic and antifungal properties, and some are associated with a toxigenic biofilm-forming strain. The findings may prove valuable to researchers in the fields of natural product discovery and toxicology.

Solubilization of the chlorin TPCS2a in the presence of Pluronic® F127/Tween 80 mixtures.

The efficacy of surfactant mixtures of Pluronic® F127 and Tween 80 at overall concentration in the micromolar range and molar ratio 1:1, 1:10, and 10:1 in inhibiting aggregation of the photosensitizer meso-tetraphenyl chlorin disulphonate (TPCS2a) was investigated in aqueous media at pH 2.9 by means of steady-state absorption and fluorescence emission spectroscopy as well as time-resolved fluorescence analysis. Corresponding experiments were performed at pH 7.4 in the absence of surfactants to determine the spectroscopic properties of a monomeric sample. Aggregation resulted in a red shift of the Soret absorption band and in substantial fluorescence quenching. The fluorescence lifetime of TPCS2a was a particularly sensitive indicator of the aggregation state, as the monomer at pH 7.4 decayed with a ∼ 10 ns time constant, while aggregation resulted in subnanosecond decay. The critical micelle concentration (CMC) of the surfactant mixtures was determined spectrophotometrically in the presence of TPCS2a. The ability of the surfactant mixtures to prevent aggregation at acidic pH was evaluated at overall surfactant concentration below and above CMC. Solubilization of TPCS2a in Pluronic® F127/Tween 80 mixtures prevented aggregation of the photosensitizer at overall surfactant concentrations much lower than those needed for both pure Pluronic® F127 and pure Tween 80.

Perioperative alcohol cessation intervention for postoperative complications.

BACKGROUND: Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures.Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery.This review was first published in 2012 and was updated in 2018. OBJECTIVES: To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption. SEARCH METHODS: We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention.We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies. DATA COLLECTION AND ANALYSIS: We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions. We presented main outcomes as dichotomous variables in a meta-analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in-hospital and 30-day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study.Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate.In-hospital and 30-day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low.Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty-one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate.All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta-analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta-analysis. No studies reported on the prevalence of participants without risky drinking in the longer term. AUTHORS' CONCLUSIONS: This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term.Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high-quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review.

Viscosity reduction of isotonic solutions of the photosensitizer TPCS2a by cyclodextrin complexation.

Meso-tetraphenyl chlorin disulphonate (TPCS2a) is a photosensitizer (PS) particularly developed and patented for use in the technology of photochemical internalization (PCI) against cancer. TPCS2a is known to aggregate in aqueous media even at low concentrations (≥0.1 µM) and to form a high-viscosity network at clinically relevant concentrations (mM). The aim of this work was to evaluate the effect of two hydroxypropylated cyclodextrin derivatives of beta and gamma type, respectively i.e. HPßCD and HPγCD, on the aggregation and solubilization of TPCS2a in isotonic solutions. Samples containing micromolar concentrations of TPCS2a were studied spectrophotometrically, while samples containing a clinical relevant concentration (10 mM = 9 mg/ml) of TPCS2a were evaluated by dynamic viscosity measurements. HPßCD was determined to be a more suitable solubilizer of TPCS2a than HPγCD in aqueous media both in the absence and presence of salt. The complexation stoichiometry between TPCS2a/HPßCD at micromolar to millimolar concentrations of TPCS2a was determined to be 1:3 and 1:2 in the absence and presence of isotonic NaCl, respectively. The network of TPCS2a (10 mM) was broken down in the presence of 3% w/v (= 20 mM) HPßCD, i.e. a 1:2 molar ratio between TPCS2a and the cyclodextrin. Formation of the inclusion complex resulted in low viscosity samples both in water and in the presence of isotonic NaCl or phosphate buffered saline (PBS) at 25 °C and 37 °C.

Evaluation of porphyrin loaded dry alginate foams containing poloxamer 407 and ß-cyclodextrin-derivatives intended for wound treatment.

Dry alginate foams intended for antibacterial photodynamic therapy (aPDT) of infected wounds were prepared. aPDT is a treatment modality involving light of appropriate wavelength, oxygen and a photosensitizer (PS) to produce radicals that attack biological targets (e.g. bacteria). The hydrophobic 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (THPP) was chosen as a model PS and loaded into the foams. The foams contained a poloxamer (Pluronic F127) and/or ß-cyclodextrin (ßCD)-derivatives, i.e. methylßCD (MßCD), heptakis(2,6-di-O-methyl)-ßCD (HkßCD) or hydroxypropylßCD (HPßCD).The physical characteristics of the various foams prepared and the THPP load, release and photostability were evaluated. All the foams were thin and flexible and could easily be handled and cut to fit a potential wound. Fast disintegration were observed for dry foams in water or phosphate buffered saline, while in Hanks' balanced salt solution the foams absorbed liquid without losing their integrity. All the foams had a similar THPP load of 0.12-0.13% w/w. The presence of ßCD-derivatives improved THPP release, however, no differences were observed between the different types of ßCD-derivatives evaluated. THPP loaded into the foams was photolabile, which induced a color change combined with fading. Alginate foams formulated with PF127, ßCD-derivatives and THPP demonstrated applicability as delivery vehicles for PSs in aPDT of wounds.

Smoking and alcohol cessation intervention in relation to radical cystectomy: a qualitative study of cancer patients' experiences.

BACKGROUND: Despite smoking and risky alcohol drinking being modifiable risk factors for cancer as well as postoperative complications, perioperative cessation counselling is often ignored. Little is known about how cancer patients experience smoking and alcohol interventions in relation to surgery. Therefore the aim of this study was to explore how bladder cancer patients experience a perioperative smoking and alcohol cessation intervention in relation to radical cystectomy. METHODS: A qualitative study was conducted in two urology out-patient clinics. We conducted semi-structured in-depth interviews with 11 purposively sampled persons who had received the smoking and alcohol cessation intervention. The analysis followed the steps contained in the thematic network analysis. RESULTS: Two global themes emerged: "smoking and alcohol cessation was experienced as an integral part of bladder cancer surgery" and "returning to everyday life was a barrier for continued smoking cessation/alcohol reduction". Participants described that during hospitalization their focus shifted to the operation and they did not experience craving to smoke or drink alcohol. Concurrent with improved well-being or experiencing stressful situations, the risk of relapse increased when returning to everyday life. CONCLUSIONS: The smoking and alcohol cessation intervention was well received by the participants. Cancer surgery served as a kind of refuge and was a useful cue for motivating patients to quit smoking and to reconsider the consequences of risky drinking. These results adds to the sparse evidence of what supports smoking and alcohol cessation in relation to bladder cancer patients undergoing major surgery and point to the need to educate healthcare professionals in offering smoking and alcohol cessation interventions in hospitals. The study also provides knowledge about the intervention in the STOP-OP study and will help guide the design of future smoking and alcohol cessation studies aimed at cancer patients undergoing surgery.

Self-reported needs for improving the supervision competence of PhD supervisors from the medical sciences in Denmark.

BACKGROUND: Quality of supervision is a major predictor for successful PhD projects. A survey showed that almost all PhD students in the Health Sciences in Denmark indicated that good supervision was important for the completion of their PhD study. Interestingly, approximately half of the students who withdrew from their program had experienced insufficient supervision. This led the Research Education Committee at the University of Copenhagen to recommend that supervisors further develop their supervision competence. The aim of this study was to explore PhD supervisors' self-reported needs and wishes regarding the content of a new program in supervision, with a special focus on the supervision of PhD students in medical fields. METHODS: A semi-structured interview guide was developed, and 20 PhD supervisors from the Graduate School of Health and Medical Sciences at the Faculty of Health and Medical Sciences at the University of Copenhagen were interviewed. Empirical data were analysed using qualitative methods of analysis. RESULTS: Overall, the results indicated a general interest in improved competence and development of a new supervision programme. Those who were not interested argued that, due to their extensive experience with supervision, they had no need to participate in such a programme. The analysis revealed seven overall themes to be included in the course. The clinical context offers PhD supervisors additional challenges that include the following sub-themes: patient recruitment, writing the first article, agreements and scheduled appointments and two main groups of students, in addition to the main themes. CONCLUSIONS: The PhD supervisors reported the clear need and desire for a competence enhancement programme targeting the supervision of PhD students at the Faculty of Health and Medical Sciences. Supervision in the clinical context appeared to require additional competence. TRIAL REGISTRATION: The Scientific Ethical Committee for the Capital Region of Denmark. Number: H-3-2010-101, date: 2010.09.29.

Interaction between the photosensitizer lumichrome and human serum albumin: effect of excipients.

Lumichrome (Lc) is a photodegradation product of riboflavin that can be used as a photosensitizer (PS) in antibacterial photodynamic therapy (aPDT). The binding of Lc with plasma proteins such as human serum albumin (HSA) could affect its efficiency as PS. Excipients are necessary to prepare stable formulations to be used in aPDT and they may affect the PS-HSA binding. Hydroxypropyl (HP)-α, ß, γ-cyclodextrin (CD), polyethylene glycol 400 (PEG400) and Pluronic® F-127 (PF127) were selected as model excipients in this study. The intrinsic HSA fluorescence quenching and absorption and fluorescence spectroscopy were used to evaluate the Lc-HSA interaction in the absence and presence of excipients. Nano-differential scanning calorimetry (DSC) was used to determine the effect of excipients on HSA. The photostability of the samples was also evaluated. The combined results showed a modest interaction between Lc and HSA which was reduced mainly by HPßCD. No major alterations of the HSA nano-DSC thermogram were observed after addition of excipients. HSA did enhance Lc photodegradation. The presence of PF127 did also induce photochemical destabilization of Lc independent of HSA. In conclusion, HPαCD, HPγCD and PEG400 seemed to be the excipients more suitable for use in topical preparations containing Lc.

Effectiveness of a Web-Based Screening and Fully Automated Brief Motivational Intervention for Adolescent Substance Use: A Randomized Controlled Trial.

BACKGROUND: Mid-to-late adolescence is a critical period for initiation of alcohol and drug problems, which can be reduced by targeted brief motivational interventions. Web-based brief interventions have advantages in terms of acceptability and accessibility and have shown significant reductions of substance use among college students. However, the evidence is sparse among adolescents with at-risk use of alcohol and other drugs. OBJECTIVE: This study evaluated the effectiveness of a targeted and fully automated Web-based brief motivational intervention with no face-to-face components on substance use among adolescents screened for at-risk substance use in four European countries. METHODS: In an open-access, purely Web-based randomized controlled trial, a convenience sample of adolescents aged 16-18 years from Sweden, Germany, Belgium, and the Czech Republic was recruited using online and offline methods and screened online for at-risk substance use using the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) screening instrument. Participants were randomized to a single session brief motivational intervention group or an assessment-only control group but not blinded. Primary outcome was differences in past month drinking measured by a self-reported AUDIT-C-based index score for drinking frequency, quantity, and frequency of binge drinking with measures collected online at baseline and after 3 months. Secondary outcomes were the AUDIT-C-based separate drinking indicators, illegal drug use, and polydrug use. All outcome analyses were conducted with and without Expectation Maximization (EM) imputation of missing follow-up data. RESULTS: In total, 2673 adolescents were screened and 1449 (54.2%) participants were randomized to the intervention or control group. After 3 months, 211 adolescents (14.5%) provided follow-up data. Compared to the control group, results from linear mixed models revealed significant reductions in self-reported past-month drinking in favor of the intervention group in both the non-imputed (P=.010) and the EM-imputed sample (P=.022). Secondary analyses revealed a significant effect on drinking frequency (P=.037) and frequency of binge drinking (P=.044) in the non-imputation-based analyses and drinking quantity (P=.021) when missing data were imputed. Analyses for illegal drug use and polydrug use revealed no significant differences between the study groups (Ps>.05). CONCLUSIONS: Although the study is limited by a large drop-out, significant between-group effects for alcohol use indicate that targeted brief motivational intervention in a fully automated Web-based format can be effective to reduce drinking and lessen existing substance use service barriers for at-risk drinking European adolescents. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Registry: ISRCTN95538913; http://www.isrctn.com/ISRCTN95538913 (Archived by WebCite at http://www.webcitation.org/6XkuUEwBx).

Interaction between curcumin and human serum albumin in the presence of excipients and the effect of binding on curcumin photostability.

Curcumin (Cur) is known to bind to human serum albumin (HSA) which may lead to a reduced phototoxic effect of the compound in the presence of serum or saliva. The influence of excipients on the Cur-HSA binding was studied by HSA florescence quenching and Cur absorption and emission spectroscopy in the presence and absence of the selected excipients. Photostabilty of Cur in the presence of HSA was evaluated, as well as the effect of excipients on HSA bound Cur photodegradation. Cyclodextrins (CDs) (2-hydroxypropyl-ß-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin) and polymers (polyethylene glycol 400, PEG 400 and Pluronic F-127, PF-127) were selected for the study. CDs and PF-127 seem to decrease Cur binding to HSA, probably through competitive binding. Cur was still bound to HSA in polyethylene glycol (PEG) solutions at the highest investigated concentration (5% w/v). However, high PEG concentration appears to have effect on the protein conformation, as shown by the fluorescence quenching study. Low Cur photostability in the presence of HSA could be improved by the addition of hydroxylpropyl-γ-cyclodextrin (HPγCD) to the samples, whereas PEG and PF-127 showed no effect.

Rheological characterization of an injectable alginate gel system.

BACKGROUND: This work investigates a general method for producing alginate gel matrices using an internal mode of gelation that depends solely on soluble alginate and alginate/gelling ion particles. The method involves the formulation of two-component kits comprised of soluble alginate and insoluble alginate/gelling ion particles. Gelling kinetics, elastic and Young's moduli were investigated for selected parameters with regard to soluble alginate guluronate content, molecular weight, calcium or strontium gelling ions and alginate gelling ion particle sizes in the range between 25 and 125 micrometers. RESULTS: By mixing the two components and varying the parameters mentioned above, alginate gel matrices with tailor-made viscoelastic properties and gelling kinetics were obtained. Final gel elasticity depended on alginate type, concentration and gelling ion. The gelling rate could be manipulated, e.g. through selection of the alginate type and molecular weight, particle sizes and the concentration of non-gelling ions. CONCLUSIONS: Formulations of the injectable and moldable alginate system presented have recently been used within specific medical applications and may have potential within regenerative medicine or other fields.