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Background: Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness)., Methods: A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I 2 -statistics., Results: Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n  = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p  < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p  < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p  < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p  = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p  = 0.007), but no difference in nausea ( p  = 0.10) or abdominal pain ( p  = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p  = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate., Conclusion: In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.

Polyvinylpyrrolidone (PVP), a polymer of the monomer N-vinylpyrrolidone with various molecular weights, was originally developed as a plasma expander. Currently, it is widely used in hair sprays, skin care products, fruit juices, and as a retarding agent in drugs such as procaine and hormones. PVP polymers with a molecular weight greater than 20,000 cannot be excreted by the kidneys and therefore are phagocytosed and permanently stored in the reticular endothelial system, leading to the so-called PVP storage disease. We report a case of localized cutaneous PVP storage disease presenting with persistent upper lip swelling and mimicking cheilitis granulomatosa, which has never been reported before.

A 59-year-old woman who had had several episodes of contact urticaria after hair treatment, developed anaphylaxis after vaginal application of povidone-iodine solution for disinfection. Prick tests showed wheal-and-flare responses to both povidone-iodine (0.1% aqueous) and polyvinylpyrrolidone (povidone, PVP) (0.001% aq.), but not to iodine or polyoxy-ethyrenenonylphenyl ether, both of which are also contained in povidone-iodine solution. We confirmed that basophils from her peripheral blood released considerable amounts of histamine on stimulation by PVPs. It appeared that both the shampoo and the permanent-wave solution contained polyvinylpyrrolidone N, N-dimethyl aminoethyl methacrylic acid copolymer diethyl sulphate solution and polyvinylpyrrolidone styrene-copolymer emulsion. Both these agents in the hair care products provoked an immediate skin response on prick testing. We speculate that sensitization to PVP had been established by these hair care products at a beauty parlor. She was recommended to avoid PVP-containing products and remained free from symptoms thereafter.

The mechanisms of the anti-inflammatory effects of corticosteroids are uncertain but could be explained by an influence on infiltrating leukocytes. Our method for the qualitative and quantitative investigation of the dermal cellular infiltrate makes it possible to study the effects of topically applied corticosteroid preparations and vehicles on the infiltrating leukocytes of normal skin, allergic and toxic reactions in guinea pig skin. Ointment and cream vehicles as well as corticosteroid cream and ointment preparations often caused erythema and increased mononuclear infiltrate after only short periods of application (24-72 h). The strongest steroid ointment gave the most marked macroscopic response and propylene glycol preparations the most marked cellular response. In both toxic and allergic reactions, application of steroid preparations after the provocation gave no beneficial result either macroscopically or microscopically. Macroscopic scores were worsened by cream and ointment preparations. Although steroid solutions had no beneficial effect, they caused no detrimental effect. The guinea pig seems to be extremely sensitive to irritants and has not proved to be a suitable model for this approach to the study of the efficacy of topically applied steroids.

Background: Pressure ulcers, also known as bedsores, decubitus ulcers and pressure injuries, are localised areas of injury to the skin or the underlying tissue, or both. Dressings are widely used to treat pressure ulcers and promote healing, and there are many options to choose from including alginate, hydrocolloid and protease-modulating dressings. Topical agents have also been used as alternatives to dressings in order to promote healing.A clear and current overview of all the evidence is required to facilitate decision-making regarding the use of dressings or topical agents for the treatment of pressure ulcers. Such a review would ideally help people with pressure ulcers and health professionals assess the best treatment options. This review is a network meta-analysis (NMA) which assesses the probability of complete ulcer healing associated with alternative dressings and topical agents., Objectives: To assess the effects of dressings and topical agents for healing pressure ulcers in any care setting. We aimed to examine this evidence base as a whole, determining probabilities that each treatment is the best, with full assessment of uncertainty and evidence quality., Search Methods: In July 2016 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, guidelines and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting., Selection Criteria: Published or unpublished randomised controlled trials (RCTs) comparing the effects of at least one of the following interventions with any other intervention in the treatment of pressure ulcers (Stage 2 or above): any dressing, or any topical agent applied directly to an open pressure ulcer and left in situ. We excluded from this review dressings attached to external devices such as negative pressure wound therapies, skin grafts, growth factor treatments, platelet gels and larval therapy., Data Collection and Analysis: Two review authors independently performed study selection, risk of bias assessment and data extraction. We conducted network meta-analysis using frequentist mega-regression methods for the efficacy outcome, probability of complete healing. We modelled the relative effectiveness of any two treatments as a function of each treatment relative to the reference treatment (saline gauze). We assumed that treatment effects were similar within dressings classes (e.g. hydrocolloid, foam). We present estimates of effect with their 95% confidence intervals for individual treatments compared with every other, and we report ranking probabilities for each intervention (probability of being the best, second best, etc treatment). We assessed the certainty (quality) of the body of evidence using GRADE for each network comparison and for the network as whole., Main Results: We included 51 studies (2947 participants) in this review and carried out NMA in a network of linked interventions for the sole outcome of probability of complete healing. The network included 21 different interventions (13 dressings, 6 topical agents and 2 supplementary linking interventions) and was informed by 39 studies in 2127 participants, of whom 783 had completely healed wounds.We judged the network to be sparse: overall, there were relatively few participants, with few events, both for the number of interventions and the number of mixed treatment contrasts; most studies were small or very small. The consequence of this sparseness is high imprecision in the evidence, and this, coupled with the (mainly) high risk of bias in the studies informing the network, means that we judged the vast majority of the evidence to be of low or very low certainty. We have no confidence in the findings regarding the rank order of interventions in this review (very low-certainty evidence), but we report here a summary of results for some comparisons of interventions compared with saline gauze. We present here only the findings from evidence which we did not consider to be very low certainty, but these reported results should still be interpreted in the context of the very low certainty of the network as a whole.It is not clear whether regimens involving protease-modulating dressings increase the probability of pressure ulcer healing compared with saline gauze (risk ratio (RR) 1.65, 95% confidence interval (CI) 0.92 to 2.94) (moderate-certainty evidence: low risk of bias, downgraded for imprecision). This risk ratio of 1.65 corresponds to an absolute difference of 102 more people healed with protease modulating dressings per 1000 people treated than with saline gauze alone (95% CI 13 fewer to 302 more). It is unclear whether the following interventions increase the probability of healing compared with saline gauze (low-certainty evidence): collagenase ointment (RR 2.12, 95% CI 1.06 to 4.22); foam dressings (RR 1.52, 95% CI 1.03 to 2.26); basic wound contact dressings (RR 1.30, 95% CI 0.65 to 2.58) and polyvinylpyrrolidone plus zinc oxide (RR 1.31, 95% CI 0.37 to 4.62); the latter two interventions both had confidence intervals consistent with both a clinically important benefit and a clinically important harm, and the former two interventions each had high risk of bias as well as imprecision., Authors' Conclusions: A network meta-analysis (NMA) of data from 39 studies (evaluating 21 dressings and topical agents for pressure ulcers) is sparse and the evidence is of low or very low certainty (due mainly to risk of bias and imprecision). Consequently we are unable to determine which dressings or topical agents are the most likely to heal pressure ulcers, and it is generally unclear whether the treatments examined are more effective than saline gauze.More research is needed to determine whether particular dressings or topical agents improve the probability of healing of pressure ulcers. The NMA is uninformative regarding which interventions might best be included in a large trial, and it may be that research is directed towards prevention, leaving clinicians to decide which treatment to use on the basis of wound symptoms, clinical experience, patient preference and cost.

Copolymers or heteropolymers are large molecules with high molecular weights (>1000 D). They have been underestimated for a long time as to their sensitizing capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a medical dressing has been described; however, the nature of the hapten is still unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone (PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene, PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and polyvinyl methyl/maleic acid anhydride.

This article describes how a model-based analysis was used to aid development of a novel formulation technology. Paracetamol (acetaminophen) was used as the motivating example with 4 different formulations (2 developmental and 2 commercial) compared using stochastic (Monte Carlo) pharmacokinetic (PK)-pharmacodynamic (PD) simulations to explore potential differences in pharmacodynamic outcomes. PK models were developed from data collected during an intensively sampled, 4-arm crossover trial in 25 fasted healthy subjects, administered 1 g of paracetamol in 4 different formulations. The PK models were linked to a previously published PD model that quantified pain relief over time following tonsillectomy. The number needed to treat (NNT) was the primary numeric used to compare effectiveness. The developmental formulations were likely to produce faster and greater analgesia with an NNT (compared with placebo) to reduce pain by 50% over a 45-minute interval post dose of 2.75 and 2.88 compared with 4.31 and 3.2 for the commercial products. Over the course of 1 hour, all formulations were comparable. The stochastic simulations provided support that the novel formulation technology was likely to provide a clinically meaningful advantage and should be developed further.

Taurolidine is an experimental antibacterial and antiendotoxic compound whose clinical utility as an antitumor agent is being investigated in human clinical trials. Taurolidine in aqueous solution exists in equilibrium with taurultam. Taurultam is subsequently transformed to taurinamide. The pharmacokinetic profiles of these metabolites are not well established. In this study, 18 healthy volunteers were administered 5.0 g of taurolidine in 250 mL of 5% polyvinylpyrrolidone in water over 2, 1, or 0.5 hours by intravenous infusion in a parallel-group design. All subjects noted discomfort at the infusion site, although there were no serious adverse events. t(max) generally occurred at the end of infusion for taurinamide, whereas that of taurultam was reached before completion of infusion. The taurolidine metabolite taurultam demonstrated a shorter half-life and lower systemic exposure than taurinamide. Shortening of infusion duration increased the C(max) and AUC of taurultam. Changes in infusion rate did not substantially change the pharmacokinetic parameters of taurinamide.

Diazolidinyl urea (DIAZ) is a formaldehyde-releasing preservative used in cosmetics and personal-care products, which has been identified as a sensitizing agent in contact dermatitis. To determine whether DIAZ sensitization is secondary to formaldehyde release or due to its own allergenic properties, we reviewed 708 consecutive patch tests of patients with various dermatologic complaints. Profiles of the 58 individuals (8%) with DIAZ sensitivity were analyzed with respect to sex, age, exposures, and chronicity of dermatitis. Significant coexistent biocide reactivity was demonstrated for DIAZ and formaldehyde (81%); 12% reacted to DIAZ alone. We conclude that the primary mode of sensitization of DIAZ is via formaldehyde release and that independent contact allergy is less frequent.

In the present study, a mixture of ammonium-bicarbonate (NH(4)HCO(3)) and sodium-chloride (NaCl) particles was used as a porogen additive to fabricate highly macroporous biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffolds. A two-step salt-leaching process was performed after the sample had become semisolidified. Compared to the standard solvent-casting/particulate-leaching (SC/PL) technique, the processing time of this approach was significantly shorter: Instead of several days, only half a day was required. In addition, the polymer/salts/solvent mixture can be easily handled and molded into scaffolds of any specific shape-for example, thin sheet, cylindrical, or bone-shaped-for special applications in tissue engineering. Our results demonstrate that these scaffolds have a highly interconnected open-pore structure as well as greater mechanical properties than those made using the standard SC/PL technique. Primary rat osteoblasts seeded into the scaffolds exhibited good seeding efficiency. The method presented here is a promising approach for fabricating scaffolds for tissue engineering applications., (Copyright 2002 Wiley Periodicals, Inc.)

Recent advances in liposome technology have shown promise relative to the introduction of chemotherapeutic agents with reduced toxicity, extended longevity, and potential for cell-specific targeting. In this study we report the engineering of a liposomal delivery system for the chemotherapeutic drug doxorubicin. The system was targeted specifically to C6 glioma in vitro by coupling transferrin to the distal ends of liposomal polyethylene glycol (PEG) chains. The transferrin receptor is overexpressed on glioma, with the extent of overexpression correlated to the severity of the tumor. Significantly increased gliomal doxorubicin uptake was achieved by drug encapsulation within transferrin-coupled liposomes compared to other liposome populations. Doxorubicin encapsulated within transferrin-coupled liposomes exhibited 70% of free doxorubicin uptake as compared to 54, 14, and 34% for non-PEG, PEG, and albumin-coupled PEG liposomes, respectively. Competitive binding assays support the receptor-mediated mechanism of targeting. The addition of one microM free transferrin reduced the uptake of doxorubicin encapsulated within transferrin-coupled liposomes by 30%., (Copyright 2000 John Wiley & Sons, Inc.)

Ketoprofen is a nonsteroidal anti-inflammatory drug with analgesic, anti-inflammatory, and antipyretic properties. Its pharmacokinetics has not been determined in small children. The objective here was to determine the pharmacokinetics of ketoprofen syrup, 0.5 mg/kg, in two groups of 10 children. Group 1 was from ages 6 months up to 2 years (7/10 younger than 1 year), and Group 2 was from ages 2 to 7 years. Venous blood samples were collected before drug administration and 0.5, 1, 2, 4, 6, 8, and 12 hours after. A validated HPLC method was used to determine plasma levels of ketoprofen. The lower limit of quantification was 0.02 microgram/ml of plasma. Ketoprofen syrup was absorbed rapidly, the plasma level reaching its maximum at 0.5 hours, with C0.5 hours = 3 micrograms/ml. The pharmacokinetics was similar between the two groups of children. The elimination half-life, 2.0 hours in Group 1 or 1.9 hours in Group 2, was similar to that reported in adults.

10 cases of contact dermatitis which began during the application of povidone-iodine preparations were examined with patch tests using 2 kinds of povidone-iodine preparations and their ingredients, i.e., povidone-iodine, polyoxyethylene nonylphenyl ether and glycerin, and also the components of povidone-iodine, i.e., iodine and polyvinylpyrrolidone. All 10 cases reacted positively to the povidone-iodine preparations and povidone-iodine, 3 out of the 10 to polyoxyethylene nonylphenyl ether, 1 out of the 9 tested to iodine, while no positive response was found to glycerin or polyvinyl-pyrrolidone. It was difficult to distinguish between allergic responses from irritation, as responses to patches of povidone-iodine and its preparations usually include irritation at high frequencies. Based on comparison of results with a control group, however, those showing + or stronger reactions to 2% povidone-iodine at days 3 to 5 were considered to be allergic. Thus, 4 out of the 10 cases were considered as sensitization to povidone-iodine. Another 3 cases were found to be polyoxyethylene nonylphenyl ether sensitized, and another 1 iodine sensitized, while the patch test reactions of the other 2 were considered to have been elicited by irritation.

The effectiveness of skin protective formulations was evaluated in a previously-described in vivo human model. All formulations failed to inhibit ammonium hydroxide and urea irritation. Only paraffin wax in cetyl alcohol statistically (p<0.01) reduced Rhus allergic contact dermatitis. 3 commercial formulations markedly (p<0.001) suppressed sodium lauryl sulfate irritation. Paraffin wax in cetyl alcohol was quantitatively the most effective formulation. These results suggest that some formulations may provide protective effects against certain, but not all, irritants or allergens.

2 acute irritants and 1 allergen were selected: sodium lauryl sulfate (SLS) representative of irritant household and occupational contact dermatitis, the combination of ammonium hydroxide (NH4OH) and urea to simulate diaper dermatitis, and Rhus to evaluate the effect of model protective materials. The putative protective materials and vehicle were applied to both ventral forearms of 10 subjects in each group, according to a randomized code. Test materials were spread over a marked 2.0 cm2 area, massaged in, allowed to dry for 30 min, and reapplied with another 30 min drying period. The model irritants and allergen were then applied (0.025 ml) to an Al-test occlusive patch, which in turn was placed for 24 h over each of the 8 designated sites. Inflammation was scored according to a clinical scale 72 h post-application. Paraffin wax plus Acetulan in cetyl alcohol, and beeswax plus Acetulan in cetyl alcohol, markedly (p < 0.001) suppressed SLS irritation. Paraffin wax plus beeswax in cetyl alcohol, and Acetulan in cetyl alcohol reduced NH4OH and urea irritation (p < 0.05), paraffin wax in cetyl alcohol significantly (p < 0.01) decreasing Rhus allergic contact dermatitis. This model, provides an easy approach to screening protectants. Its clinical significance requires comparison with an open rather than an occluded challenge.

The absorption characteristics of ethiofos were studied using the rat in situ intestine circulating perfusion technique. Slow absorption kinetics were observed for ethiofos with varying rates of absorption and metabolism/degradation in situ as a function of buffer and absorption enhancers. In most cases less than 10 per cent of the radiolabeled compound is lost from the circulating perfusate in 90 min. In addition, over the same time period greater than 40 per cent of the intact parent compound was lost by degradation. Much of the difference can be accounted for in the formation of the free thiol metabolite. WR-1065, suggesting ester hydrolysis or metabolic activity. Good stability was observed in all perfusate systems ex vivo indicating that the degradation occurs in situ. The disodium salt of ethylenediaminetetraacetic acid (EDTA) was shown to be an effective absorption enhancer of ethiofos. The enhancement of intestinal absorption by EDTA was dose-dependent resulting in a 20-fold increase in blood levels of ethiofos in the portal blood. Follow-up studies in the rhesus monkey confirm this observation. Salicylate and dimethylsulfoxide (DMSO) also resulted in absorption enhancement although to a lesser degree than that seen after EDTA treatment. Addition of several alkaline phosphatase inhibitors did not significantly improve absorption of ethiofos in the rat small intestine. Proposed mechanism(s) for intestinal absorption and absorption enhancement of ethiofos are discussed.

Kathon CG is a very well studied preservative used in cosmetics and toiletries. It is effective in low concentrations (3 to 15 ppm active ingredients) and exhibits outstanding antimicrobial activity against gram-negative and gram-positive bacteria, yeasts and fungi. Although this biocide is not considered to pose a toxicological hazard at recommended use levels, the sensitizing potential of Kathon CG has been established. From November 1988 to June 1989, we patch tested 626 unselected contact dermatitis patients with Kathon CG solution containing 200 ppm active ingredients and obtained 22 (3.5%) positive reactions. Relevance was established in 7 of the 22 patients. Women were predominantly sensitized, the principal source of sensitization being cosmetics.

Kathon CG was determined in 156 of the most commonly used cosmetic products in Denmark. 42% of the cosmetic products were found to contain Kathon CG. Kathon CG was present in 48% of "rinse off" and 31% of "leave on" cosmetic products. The 3:1 ratio of chloromethyl isothiazolinone (CMI): methyl isothiazolinone (MI) in Kathon CG was found to be disturbed in 41% of Kathon CG preserved cosmetic products. The disturbed CMI/MI ratio was shown in 29% "rinse off" and 73% "leave on" cosmetic products. It is suggested that the chemical reaction of the ketone group of the isothizaolinones with other ingredients in cosmetic products may disturb the CMI/MI ratio of Kathon CG. The results of the study have been discussed in relation to the use of Kathon CG in cosmetic products as well as test material for allergic reaction.