Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs.

The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5mg/ml. SEDDS were characterized regarding size distribution, zeta potential, stability towards lipase, log DSEDDS/release medium and mucus diffusion behavior. The oral bioavailability of octreotide was evaluated in pigs via LC-MS/MS analyses. Most efficient ion pairing was achieved at a molar ratio of 1:3 (peptide: surfactant). SEDDS containing the octreotide-deoxycholate, -decanoate and -docusate ion pair exhibited a mean droplet size of 152nm, 112nm and 191nm and a zeta potential of -3.7, -4.6 and -5.7mV, respectively. They were completely stable towards degradation by lipase and showed a log DSEDDS/release medium of 1.7, 1.8 and 2.7, respectively. The diffusion coefficient of these SEDDS was in the range of 0.03, 0.11 and 0.17×10-9cm2/s, respectively. In vivo studies with these HIPs showed no improvement in the oral bioavailability in case of octreotide-decanoate. In contrast, octreotide-deoxycholate and octreotide-docusate SEDDS resulted in a 17.9-fold and 4.2-fold higher bioavailability vs. CONTROL: According to these results, hydrophobic ion pairing could be identified as a key parameter for SEDDS to achieve high oral bioavailability.

A multistate investigation of health care-associated Burkholderia cepacia complex infections related to liquid docusate sodium contamination, January-October 2016.

BACKGROUND: Outbreaks of health care-associated infections (HAIs) caused by Burkholderia cepacia complex (Bcc) have been associated with medical devices and water-based products. Water is the most common raw ingredient in nonsterile liquid drugs, and the significance of organisms recovered from microbiologic testing during manufacturing is assessed using a risk-based approach. This incident demonstrates that lapses in manufacturing practices and quality control of nonsterile liquid drugs can have serious unintended consequences. METHODS: An epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred among critically ill, hospitalized, adult and pediatric patients was performed between January 1, 2016, and October 31, 2016. RESULTS: One hundred and eight case patients with Bcc infections at a variety of body sites were identified in 12 states. Two distinct strains of Bcc were obtained from patient clinical cultures. These strains were found to be indistinguishable or closely related to 2 strains of Bcc obtained from cultures of water used in the production of liquid docusate, and product that had been released to the market by manufacturer X. CONCLUSIONS: This investigation highlights the ability of bacteria present in nonsterile, liquid drugs to cause infections or colonization among susceptible patients. Prompt reporting and thorough investigation of potentially related infections may assist public health officials in identifying and removing contaminated products from the market when lapses in manufacturing occur.

Association of Dissemination of an Educational Communication Tool With Docusate Administration.

Importance: A clear message and call to action can affect the use of a medication with limited efficacy. Objectives: To assess the association of the dissemination of an educational document about the lack of efficacy of docusate with docusate administration and whether changing docusate administration was associated with a change in administration of comparable laxatives. Design, Setting, and Participants: In this quasi-experimental, pre-post study of all acute care and continuing care facilities serviced by Alberta Health Services in Alberta, Canada, an interrupted time series analysis was performed to examine the association of an educational communication tool with docusate administration from June 1, 2014, through May 31, 2016. Interventions: A Drugs & Therapeutics Backgrounder was disseminated to all pharmacists in December 2014. Backgrounders are academic detailing tools to assist pharmacists in supporting drug stewardship and are supplemented by online, interactive webinars. Main Outcomes and Measures: This study examined whether a decrease in docusate administration across the organization occurred after release of the backgrounder. Messaging in the backgrounder stated that, unless clinically necessary, docusate should not be replaced by another medication. This study assessed whether that message was accepted by measuring administration of comparable laxatives. Study medication administration is reported as defined daily doses (DDDs) per 1000 inpatient-days (PDs). Rates were compared for the 6 months before the intervention and 3, 6, 12, and 18 months after intervention. Results: Among the 111 acute care facilities (8500 beds) and 24 000 long-term care beds of the Alberta Health Services, predicted docusate administration decreased from preintervention (474 DDDs/1000 PDs) to 3 months (321 DDDs/1000 PDs; 95% CI, 304-465 DDDs/1000 PDs), 6 months (296 DDDs/1000 PDs; 95% CI, 277-456 DDDs/1000 PDs), 12 months (251 DDDs/1000 PDs; 95% CI, 207-499 DDDs/1000 PDs), and 18 months (214 DDDs/1000 PDs; 95% CI, 148-536 DDDs/1000 PDs). Administration of the comparable laxatives did not statistically significantly change (preintervention: 627 DDDs/1000 PDs; 18 months after intervention: 702 DDDs/1000 PDs; 95% CI, 295-694 DDDs/1000 PDs; P = .13). Conclusions and Relevance: A communication document supported by live presentations was associated with decreased administration of docusate up to 6 months, with a leveling of the association after 1 year. Significant systemic change can be achieved without extensive and complex interventions if the evidence and messaging are aligned.

Hydrophobic ion pairing: Key to highly payloaded self-emulsifying peptide drug delivery systems.

AIM: The aim of this study was the formation and characterization of various ion pairs of therapeutic peptides with different surfactants in order to reach a high payload in self-emulsifying drug delivering systems (SEDDS). METHODS: Hydrophobic ion pairs (HIP) were formed between the anionic surfactants sodium docusate, dodecylsulfate and oleate and the peptides leuprorelin (LEU), insulin (INS) and desmopressin (DES). The efficiency of HIP formation was evaluated by quantifying the amount of formed complexes, log P value determination in n-octanol/water via HPLC and zeta potential measurements. Solvents and surfactants were screened regarding their complex solubilizing properties. Subsequently, peptide complexes were incorporated into SEDDS followed by payload and stability determination. RESULTS: Independent from the type of peptide, docusate showed the most efficient HIP properties followed by dodecylsulfate and oleate. Ratios of 2:1 for LEU, 6:1 for INS and 1.5:1 for DES led to the highest quantity of formed complexes with docusate and log P increased at least by 3 units. The more docusate was added to each peptide, the more negative became the zeta potential of the resulting complex. Incorporating these optimized complexes into novel SEDDS containing Capryol 90, Labrafil M 2125 CS, Labrasol ALF, Peceol, propylene glycol, tetraglycol, Transcutol HP and Tween 20 allowed payloads of the LEU, DES and INS complexes above 10%. Moreover, SEDDS exhibited high stability and constant negative zeta potential over a 4h incubation time. CONCLUSION: Following the procedure described herein payloads >10% can be achieved for peptide drugs in SEDDS.

Changing clinical guidelines from delayed to early aperient administration for enterally fed intensive care patients was associated with increased diarrhoea: a before-and-after, intention-to-treat evaluation.

BACKGROUND: The 14-bed intensive care unit of a tertiary referral hospital adopted a guideline to start docusate sodium with sennosides when enteral nutrition was started. This replaced a guideline to start aperients after 24h of enteral nutrition if no bowel action had occurred. We sought to determine the effect of this change on the incidence of diarrhoea and constipation in intensive care. METHODS: Retrospective audit of the medical records of consecutive adult patients admitted to intensive care and given enteral nutrition, excluding those with a primary gastrointestinal system diagnosis, between Jan-Aug 2011 (the delayed group, n=175) and Jan-Aug 2012 (the early group, n=175). The early aperient guideline was implemented during Sep-Dec 2011. RESULTS: The early and delayed groups were similar in age (median 62 years vs. 64 years; P=0.17), sex (males 65% vs. 63%; P=0.91), and postoperative cases (31% vs. 33%; P=0.82) and had similar proportions who received mechanical ventilation (95% vs. 95%; P=1.00), an inotrope or vasopressor (63% vs. 70%; P=0.17), renal replacement therapy (8% vs. 10%; P=0.71), opiates (77% vs. 80%; P=0.60), antibiotics (89% vs. 91%; P=0.72) and metoclopramide (46% vs. 55%; P=0.11). A significantly larger proportion of the early group received an aperient (54% vs. 29%, P<0.001) and experienced diarrhoea (38% vs. 27%, P=0.04), but the groups had similar proportions affected by constipation (42% vs. 43%, P=0.91). CONCLUSIONS: Changing guidelines from delayed to early aperient administration was associated with an increase in the incidence of diarrhoea but was not associated with the incidence of constipation. These findings do not support changing guidelines from delayed to early aperient administration.

Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system.

Carrier with high drug loading content is one of the most important issues in drug delivery system. In the present work, an ion-pair amphiphilic molecule composed of anticancer drug cation and surfactant anion is used for straightforward fabricating vesicles for cancer therapy. Anticancer drug (cytarabine hydrochloride) and anionic surfactant (AOT) are selected for the fabrication of ion-pair amphiphilic molecule. One amphiphilic molecule contains one drug cation, thus the drug loading content is 50% (mol/mol) in theory. The in vitro drug release study shows that the release time of cytarabine is about 3 times of the pure cytarabine solution and the permeability of cytarabine has been improved about 160 times tested by parallel artificial membrane permeability assay model. However, the hemolytic toxicity is largely decreased in the studied concentration range. The in vitro cytotoxicity results show that cytarabine-AOT amphiphiles have a much lower IC50 (drug concentration resulting in 50% cell death) value and a higher cell inhibition rate comparing with their respective components, indicating its effective therapy for leukemic cells. To obtain a longer and a convenient drug release system, the prepared vesicles are further incorporated into the thermosensitive PLGA-PEG-PLGA hydrogel to prepare a subcutaneous administration. The in vivo drug release results indicate that cytarabine-AOT vesicle-loaded hydrogel is a good injectable delivery system for controlled release of cytarabine for cancer therapy.

Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients.

CONTEXT: The stool softener docusate is widely used in the management of constipation in hospice patients. There is little experimental evidence to support this practice, and no randomized trials have been conducted in the hospice setting. OBJECTIVES: To assess the efficacy of docusate in hospice patients. METHODS: This was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. Patients were included if they were age 18 years or older, able to take oral medications, did not have a gastrointestinal stoma, and had a Palliative Performance Scale score of 20% or more. The primary outcome measures were stool frequency, volume, and consistency. Secondary outcomes were patient perceptions of bowel movements (difficulty and completeness of evacuation) and bowel-related interventions. RESULTS: A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were neither significant differences between the groups in stool frequency, volume, or consistency, nor in difficulty or completeness of evacuation. On the Bristol Stool Form Scale, more patients in the placebo group had Type 4 (smooth and soft) and Type 5 (soft blobs) stool, whereas in the docusate group, more had Type 3 (sausage like) and Type 6 (mushy) stool (P=0.01). CONCLUSION: There was no significant benefit of docusate plus sennosides compared with placebo plus sennosides in managing constipation in hospice patients. Docusate use should be considered on an individual basis.

Distribution of polyphenols and a surfactant component in skin during Aerosol OT microemulsion-enhanced intradermal delivery.

As for most other polyphenols, intradermal delivery of curcumin and resveratrol is limited; however, it was significantly improved by a microemulsion using Aerosol OT (Aerosol OT microemulsion) and Tween 80 (Tween 80 microemulsion) as surfactants. Aerosol OT microemulsion was more effective and the incorporation ratio of these polyphenols into skin by Aerosol OT microemulsion was five-fold or ten-fold that by Tween 80 microemulsion. To clarify the mechanism of the enhancement we examined the distribution of these polyphenols and the surfactant component, Aerosol OT, using excised guinea pig skin and Yucatan micropig (YMP) skin. During permeation, polyphenols distributed deep in the skin. In particular, a small molecule, resveratrol, was mainly present in the dermis in YMP skin. Aerosol OT also distributed deep in the skin. These findings suggest the possible involvement of the interaction of surfactant molecules with skin components in the enhanced delivery process of polyphenols. The distribution ratio between the dermis and epidermis of the polyphenols, including quercetin, in the presence of Aerosol OT microemulsion decreased with the increase of molecular weight in YMP skin, suggesting the possibility that distribution to the dermis is regulated by the molecular size.

Bowel function after minimally invasive urogynecologic surgery: a prospective randomized controlled trial.

OBJECTIVES: The goals of this study were to assess the effect of a standardized postoperative bowel regimen of over-the-counter medications on (1) time to first bowel movement (BM) and (2) pain level associated with first BM in subjects undergoing minimally invasive urogynecologic surgery. METHODS: Eligible patients scheduled to undergo minimally invasive urogynecologic surgery were offered participation. Enrolled subjects were randomized by computerized schedule. Demographic and perioperative data were collected. Subjects completed a validated questionnaire preoperatively and postoperatively assessing preexisting constipation, frequency and consistency of bowel movements, use of pain medications, mean daily pain level (using visual analog scale), stool consistency, and pain associated with first postoperative bowel movement. The control group was instructed to take docusate sodium twice daily postoperatively. The treatment group took docusate sodium plus Miralax, fiber wafers, and bisacodyl suppositories as directed by protocol. Wilcoxon or t testing was used to compare continuous variables; χ testing was used for categorical relationships, and backward-elimination multiple regression was used to assess independent effects. RESULTS: Seventy-two subjects were enrolled and randomized. Twelve subjects withdrew, leaving 60 (30 per group) completing the study. There were no statistically significant differences between groups in baseline characteristics. Mean (SD) age was 63 (9) years for the control group and 58 (10) for the study group (P = 0.06). Mean pelvic organ prolapse stage was III in each group. The mean (SD) operating room time was 198 (65) minutes for the controls and 216 (74) for the study subjects. Sixty-five percent underwent robot-assisted surgery (50% hysterectomy and 63% sacrocolpopexy). Ninety-eight percent of surgeries were performed under general anesthesia.Before adjustment, the mean (SD) time to first BM was 77 (24) hours in controls versus 64 (21) in the study patients (P = 0.03). Using multiple regression, baseline frequency of defecation (1-2 BMs/wk) was directly associated with the time to first BM (added 25.2 hours; P = 0.009) and being in the study group was inversely associated (first BM, 11.7 hours sooner; P = 0.04). No other variables were retained.There was no difference in pain associated with first postoperative BM (visual analog scale, 3.6 (3.2) vs 3.7 (2.8); P = 0.98), but those with prior complaints of vaginal or rectal splinting had higher pain scores (1.9 and 2.8 points higher, respectively; P = 0.04 for both). There was a trend toward higher pain scores with higher postoperative daily narcotic intake (P = 0.06). No other variables were retained.There was a significant difference in recorded compliance between control versus study regimens (94% vs 81%, respectively; P = 0.002). CONCLUSIONS: Mean time to first postoperative BM after minimally invasive urogynecologic surgery is more than 3.5 days with use of docusate sodium alone and is only slightly shorter when combination therapy is used. First BM after surgery is considered to be painful despite the use of medications. Future studies targeting postoperative discomfort/pain with defecation could target preoperative bowel regimens or more aggressive postoperative interventions. Regimens should remain simple to increase compliance.

Strategic pain management: the identification and development of the IAHPC opioid essential prescription package.

The aim of this study was to determine by consensus the components of an opioid essential prescription package (OEPP) to be used when initiating a prescription for the control of moderate to severe chronic pain. Palliative care physicians (n=60) were sampled from the International Association for Hospice and Palliative Care (IAHPC) membership list to represent a range of countries of varying economic levels and diverse geographical regions. Using a Delphi study method, physicians were asked to rank preferences of drug and dosing schedule for first-line opioid, antiemetic, and laxative for the treatment of adults with chronic pain due to cancer and other life-threatening conditions. Overall response rates after two Delphi survey rounds were 95% (n=57) and 82% (n=49), respectively. A consensus (set at ≥75% agreement) was reached to include morphine as first-line opioid at a dose of 5 mg orally every 4 hours. Consensus was reached to include metoclopramide as a first-line antiemetic, but there was no consensus on "regular" or "as needed" administration. No consensus was reached regarding a first-line laxative, but a combination of senna and docusate secured 59% agreement. There was consensus (93% agreement) that laxatives should always be given regularly when opioid treatment is started. Further work is needed to establish a recommended dose of metoclopramide and a type and dose of laxative. The resulting OEPP is international in scope and is designed to ensure that opioids are better tolerated by reducing adverse effects of opioids, which could lead to more sustained improvements in pain management.

The use of senna with docusate for postoperative constipation after pelvic reconstructive surgery: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The objective of the study was to compare time to first bowel movement (BM) after surgery in subjects randomized to placebo or senna with docusate. STUDY DESIGN: Ninety-six subjects completed a baseline 7-day bowel diary before and after surgery. After pelvic reconstructive surgery, the subjects were randomized to either placebo (n=45) or senna (8.6 mg) with docusate (50 mg) (n=48). Time to first BM and postoperative use of magnesium citrate were compared. RESULTS: There was a significant difference in the time to first BM in those receiving senna with docusate vs placebo (3.00+/-1.50 vs 4.05+/-1.50 days; P<.002). More subjects in the placebo group needed to use magnesium citrate to initiate a bowel movement (43.6% vs 7.0%; P<.001). CONCLUSION: The use of senna with docusate decreases time to first BM in those undergoing pelvic reconstructive surgery compared with placebo. Subjects using senna with docusate are also significantly less likely to use magnesium citrate.

Rectal fecal impaction treatment in childhood constipation: enemas versus high doses oral PEG.

OBJECTIVE: We hypothesized that enemas and polyethylene glycol (PEG) would be equally effective in treating rectal fecal impaction (RFI) but enemas would be less well tolerated and colonic transit time (CTT) would improve during disimpaction. METHODS: Children (4-16 years) with functional constipation and RFI participated. One week before disimpaction, a rectal examination was performed, symptoms of constipation were recorded, and the first CTT measurement was started. If RFI was determined, then patients were assigned randomly to receive enemas once daily or PEG (1.5 g/kg per day) for 6 consecutive days. During this period, the second CTT measurement was started and a child's behavior questionnaire was administered. Successful rectal disimpaction, defecation and fecal incontinence frequencies, occurrence of abdominal pain and watery stools, CTTs (before and after disimpaction), and behavior scores were assessed. RESULTS: Ninety-five patients were eligible, of whom 90 participated (male, n = 60; mean age: 7.5 +/- 2.8 years). Forty-six patients received enemas and 44 PEG, with 5 dropouts in each group. Successful disimpaction was achieved with enemas (80%) and PEG (68%; P = .28). Fecal incontinence and watery stools were reported more frequently with PEG (P < .01), but defecation frequency (P = .64), abdominal pain (P = .33), and behavior scores were comparable between groups. CTT normalized equally (P = .85) in the 2 groups. CONCLUSION: Enemas and PEG were equally effective in treating RFI in children. Compared with enemas, PEG caused more fecal incontinence, with comparable behavior scores. The treatments should be considered equally as first-line therapy for RFI.

Magnetic resonance colonography without bowel cleansing using oral and rectal stool softeners (fecal cracking)--a feasibility study.

The aim of our study was to assess the effect of oral and rectal stool softeners on dark-lumen magnetic resonance (MR) colonography without bowel cleansing. Ten volunteers underwent MR colonography without colonic cleansing. A baseline examination was performed without oral or rectal administration of stool softeners. In a second set, volunteers ingested 60 ml of lactulose 24 h prior to MR examination. In a third examination, water as a rectal enema was replaced by a solution of 0.5%-docusate sodium (DS). A fourth MR examination was performed, in conjunction with both oral administration of lactulose and rectal application of DS. A T1-weighted data set was acquired at scanning times of 0, 5 and 10 min after colonic filling. A fourth data set was acquired 75 s after i.v. injection of contrast agent. Signal intensity of stool was calculated for all colonic segments. Without oral ingestion of lactulose or rectal enema with DS stool signal intensity was high and did not decrease over time. However, lactulose and DS caused a decrease in stool signal intensity. Both substances together led to a decreasing signal intensity of feces. Combination of lactulose and DS provided the lowest signal intensity of stool. Thus, feces could hardly be distinguished from dark rectal enema allowing for the assessment of the colonic wall.

IPM/DOSS/water microemulsions as reactors for silver sulfadiazine nanocrystal synthesis.

The first goal of this work was the preparation of a water-in-oil microemulsion from components generally regarded as safe for use in humans. Stable formulations without need of a co-surfactant were prepared from isopropyl myristate (IPM), dioctyl sodium sulfosuccinate (DOSS), and water. A ternary phase diagram was prepared for the IPM/DOSS/water system. The IPM/DOSS/water microemulsions were characterized by conductivity and dynamic laser light scattering (DLS). The results obtained from conductivity experiments indicate conductivity values of less than 1 muS/cm and were consistent with the formation of w/o microemulsions. The DLS results showed that the emulsified water droplets had an average diameter range of 9.2 to 19.7 nm, depending on composition. Modulation of the droplet size is possible by varying the water to DOSS molar ratio and DOSS to IPM ratio. The second goal of this work was the preparation of silver sulfadiazine (AgSD) nanoparticles. It was hypothesized that two separate microemulsions containing dispersed aqueous droplets of either sodium sulfadiazine or silver nitrate would react when mixed. The DLS results are consistent with the successful formation of submicron AgSD crystals.

Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.

BACKGROUND: The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort. OBJECTIVE: To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS. METHODS: Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain. RESULTS: Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were reported among 23 (72%) participants, resulting in a cold sore incidence rate of 19.8 per 100 person-months of observation. Online data were available for 32 outbreaks; the absence of a resolution date made it impossible to accurately calculate the duration of 12 (38%) outbreaks. Although the DSS treatment group had a shorter mean outbreak duration (6.6 vs 7.7 days, P =.2) and fewer mean days to crust formation (3.5 vs 4.9, P =.1), these differences did not reach statistical significance. The DSS group has statistically significant lower mean pain scores (3.1 vs 7.6, P =.04), but participants in this group also consumed more acetaminophen tablets than the placebo group (1.1 versus 0.5, P=.55). Adherence to medication was similar in both groups: 7 (50%) of the verum group reported using the cream as directed compared to 6 (46.2%) in the placebo group; (P =.8). CONCLUSIONS: We efficiently recruited participants and achieved high overall retention rates. However, participant adherence to the daily outbreak visit schedules was low and only 7 (50%) participants used the cream as directed. These limitations could be addressed in future Internet-based studies by using Personal Digital Assistants (PDAs), using reminder devices, and providing incentives. By enhancing participant adherence, clinical trials requiring frequent participant contact may be feasible over the Internet.

Randomized clinical trial of docusate, triethanolamine polypeptide, and irrigation in cerumen removal in children.

BACKGROUND: Cerumen obstructing visualization of the tympanic membrane in children is a common and frustrating problem. Docusate sodium, triethanolamine polypeptide, and saline were compared to determine their effectiveness in relieving cerumen obstruction in children. METHODS: A randomized, controlled, double-blind trial was performed on pediatric patients aged 6 months through 5 years with cerumen obstruction. The enrolling physician determined whether the cerumen completely or partially obstructed visualization of the tympanic membrane. One milliliter of docusate sodium, triethanolamine polypeptide, or normal saline as control was placed into the patient's ear canal. If the tympanic membrane was not completely visualized after 15 minutes, the ear was irrigated with 50 mL of tepid water. Irrigation was repeated a second time if needed. The main outcome was the proportion of tympanic membranes that were completely visualized after cerumeno-eblytic agents or control saline, alone or with irrigation if needed. RESULTS: Of 92 patients enrolled, 34 received docusate sodium; 30, triethanolamine polypeptide; and 28, saline. Mean +/- SD patient age was 34.7 +/- 18.1 months, and 50 (54%) of the patients were girls. Groups were similar in age, race, sex, ear enrolled, wax consistency, and degree of obstruction. There was no significant difference in the proportion of tympanic membranes completely visualized after treatment with docusate (18/34; 53%), triethanolamine polypeptide (13/30; 43%), or saline (19/28; 68%) (P =.17). CONCLUSION: Application of docusate sodium or triethanolamine polypeptide did not significantly improve the proportion of tympanic membranes that were completely visualized vs application of the saline control.

Insulin inhalation with absorption enhancer at meal-times results in almost normal postprandial insulin profiles.

BACKGROUND: Conventional insulin therapy with subcutaneous injections of regular insulin at meal-times result in plasma insulin peaks that are lower and appear later than meal related insulin peaks in healthy individuals. The present study was designed in order to evaluate the resulting insulin concentrations in peripheral blood after inhalation of micro crystalline human insulin together with an absorption enhancer [dioctyl sodium sulphosuccinate (DOSS)] via a powder inhaler. METHODS: Ten insulin dependent middle-aged non-obese diabetic patients (mean diabetes duration 21 years) were included. Blood samples for glucose and insulin were taken immediately before and 13 times, up to 300 min, after insulin inhalation. The mass median aerodynamic diameter of the particles was 3.2 microm. The inhaled insulin dose was 39 U. RESULTS: Within 5 min after the end of the 2 min inhalation procedure the mean increase of insulin was 7.0 microU ml-1, and the mean maximum concentration, 12.1 microU ml-1, was reached between 20 and 30 min. There was then a slow decline until base-line was reached after around 210 min and there were no adverse events. CONCLUSIONS: Inhalation of a mixture of 39 U of insulin and enhancer resulted in a rapid plasma insulin peak with a slow decline, similar to the normal postprandial insulin profile.