Withdrawal Procedure Research Articles

Impact of efficacy at the μ-opioid receptor on antinociceptive effects of combinations of μ-opioid receptor agonists and cannabinoid receptor agonists.

Cannabinoid receptor agonists, such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC), enhance the antinociceptive effects of μ-opioid receptor agonists, which suggests that combining cannabinoids with opioids would improve pain treatment. Combinations with lower efficacy agonists might be preferred and could avoid adverse effects associated with large doses; however, it is unclear whether interactions between opioids and cannabinoids vary across drugs with different efficacy. The antinociceptive effects of μ-opioid receptor agonists alone and in combination with cannabinoid receptor agonists were studied in rhesus monkeys (n = 4) using a warm water tail withdrawal procedure. Etorphine, fentanyl, morphine, buprenorphine, nalbuphine, Δ(9)-THC, and CP 55,940 (2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol) each increased tail withdrawal latency. Pretreatment with doses of Δ(9)-THC (1.0 mg/kg) or CP 55,940 (0.032 mg/kg) that were ineffective alone shifted the fentanyl dose-effect curve leftward 20.6- and 52.9-fold, respectively, and the etorphine dose-effect curve leftward 12.4- and 19.6-fold, respectively. Δ(9)-THC and CP 55,940 shifted the morphine dose-effect curve leftward only 3.4- and 7.9-fold, respectively, and the buprenorphine curve only 5.4- and 4.1-fold, respectively. Neither Δ(9)-THC nor CP 55,940 significantly altered the effects of nalbuphine. Cannabinoid receptor agonists increase the antinociceptive potency of higher efficacy opioid receptor agonists more than lower efficacy agonists; however, because much smaller doses of each drug can be administered in combinations while achieving adequate pain relief and that other (e.g., abuse-related) effects of opioids do not appear to be enhanced by cannabinoids, these results provide additional support for combining opioids with cannabinoids to treat pain.

Changes in the Regulatory Base of the Budget Process in September 2013

The Government of the Russian Federation has issued documents which introduce from 2014 a simplified procedure for withdrawal of land plots from public (municipal) entities and state-owned enterprises in favor of the state treasury; amendments were introduced in to the procedure for provision of state guarantees on loans attracted by enterprises of the defense industry complex.

Rapid opiate detoxification and antagonist induction under general anaesthesia or intravenous sedation is humane, sometimes essential and should always be an option. Three illustrative case reports involving diabetes and epilepsy and a review of the literature

When abstinence is an appropriate goal, controlled studies and systematic reviews confirm that rapid, antagonist-precipitated opiate withdrawal procedures are the most effective and cost effective methods of initiating abstinence, and naltrexone (NTX) maintenance. While 'rapid' withdrawal, better conceptualised as Rapid Antagonist Induction (RAI), can often be humanely achieved with modest sedation levels, we present three case histories to support our argument that for some patients, general anaesthesia (GA), or techniques of intravenous sedation (IVS) that approach GA, are essential for safety and success. This includes patients with intercurrent disease (e.g. epilepsy or insulin-dependent diabetes) but also those with severe withdrawal phobia after previous distressing experiences. We discuss the history of the procedure. The dangers of RAI under GA or IVS in experienced hands have been exaggerated and the appropriate expertise should be more easily available. Patients and clinicians readily accept risks of major surgery for the excessive intake of food that causes most obesity. Similar risk-acceptance exists in cosmetic surgery and obstetrics. The increasing use and effectiveness of long-acting implants or depot-injections of NTX for relapse-prevention have largely solved compliance problems that undermined the potential of oral NTX. Their ability to prevent opiate overdose in abstinent, non-tolerant patients also strengthens arguments both for offering RAI as a therapeutic option and for reducing psychological, professional and practical barriers to using it.

Variability in management of implantable ports in oncology outpatients

Purpose of the researchTo describe the variability in practice regarding the management of vascular access ports in adult oncology patients at Spanish outpatient clinics and to evaluate its compliance with the recommended procedural guidelines. Methods and sampleThree e-mailings or three postal mail-outs were sent to all Spanish outpatient clinics, in accordance with the hospital's preference. An additional fourth postal mail-out was made to all units. In total 185 units at Spanish outpatient clinics out of a total 256 completed the survey questionnaire. Key resultsA number of variations exist in the techniques used for insertion, withdrawal of needle from vascular access ports, blood sampling and unblocking procedure. There is considerable agreement in relation to the use of a special beveled needle, the use of gloves in the access and withdrawal procedures and checking of reservoir permeability by aspirating blood. In most cases, sterile gloves are used but there is a lesser occurrence of both scrubbed hands and correct antiseptic use. ConclusionsThere are considerable differences in the management of the vascular access ports in terms of the recommendations published in the main international guidelines, though these are based on low level evidence. The results highlight the need for further quality studies in ports use and manipulation to lessen the variability between published recommendations and clinical practice.

Thermal sensitivity across ages and during chronic fentanyl administration in rats

Chronic pain is becoming a more common medical diagnosis and is especially prevalent in older individuals. As such, prescribed use of opioids is on the rise, even though the efficacy for pain management in older individuals is unclear. Thus, the present preclinical study assessed the effectiveness of chronic fentanyl administration to produce antinociception in aging rats (16, 20, and 24months). Animals were tested in a thermal sensitivity procedure known to involve neural circuits implicated in chronic pain in humans. Sensitivity to heat and cold thermal stimulation was assessed during 28days of fentanyl administration (1.0mg/kg/day), and 28days of withdrawal. Fentanyl resulted in decreased thermal sensitivity to heat but not cold stimulation indicated by more time spent in the hot compartment relative to time spent in the cold or neutral compartments. Unlike previous findings using a hot-water tail withdrawal procedure, tolerance did not develop to the antinociceptive effects of fentanyl over a 28-day period of drug administration. The oldest animals were least sensitive, and the youngest animals most sensitive to the locomotor-stimulating effects of fentanyl. The effect on the antinociceptive response to fentanyl in the oldest group of rats was difficult to interpret due to profound changes in the behavior of saline-treated animals. Overall, aging modifies the behavioral effects of opioids, a finding that may inform future studies for devising appropriate treatment strategies.

Changes in the Regulatory Base of the Budgetary Process in May 2013

In June 2013, in the regulatory base of the budgetary process the following developments took place: the administrative procedure for withdrawal of land plots allocated to state or municipal entities and state-run enterprises; the grounds have been expanded for provision of budget allocations out of the reserve fund of the Government of the Russian Federation to federal executive authorities and executive authorities of constituent entities of the Russian Federation for partial reimbursement of expenditures related to financial support of measures aimed at liquidation of emergency situations.

Forced withdrawal from methadone maintenance therapy in criminal justice settings: A critical treatment barrier in the United States

The World Health Organization classifies methadone as an essential medicine, yet methadone maintenance therapy remains widely unavailable in criminal justice settings throughout the United States. Methadone maintenance therapy is often terminated at the time of incarceration, with inmates forced to withdraw from this evidence-based therapy. We assessed whether these forced withdrawal policies deter opioid-dependent individuals in the community from engaging methadone maintenance therapy in two states that routinely force inmates to withdraw from methadone (N=205). Nearly half of all participants reported that concern regarding forced methadone withdrawal during incarceration deterred them engaging methadone maintenance therapy in the community. Participants in the state where more severe methadone withdrawal procedures are used during incarceration were more likely to report concern regarding forced withdrawal as a treatment deterrent. Methadone withdrawal policies in the criminal justice system may be a broader treatment deterrent for opioid-dependent individuals than previously realized. Redressing this treatment barrier is both a health and human rights imperative.

Increased impulsive choice for saccharin during PCP withdrawal in female monkeys: influence of menstrual cycle phase.

In previous studies with male and female rhesus monkeys, withdrawal of access to oral phencyclidine (PCP) self-administration reduced responding for food under a high fixed-ratio (FR) schedule more in males than females, and with a delay discounting (DD) task with saccharin (SACC) as the reinforcer impulsive choice for SACC increased during PCP withdrawal more in males than females. The goal of the present study was to examine the effect of PCP (0.25 or 0.5mg/ml) withdrawal on impulsive choice for SACC in females during the follicular and luteal phases of the menstrual cycle. In component 1, PCP and water were available from two drinking spouts for 1.5h sessions under concurrent FR 16 schedules. In component 2, a SACC solution was available for 45min under a DD schedule. Monkeys had a choice of one immediate SACC delivery (0.6ml) or six delayed SACC deliveries, and the delay was increased by 1s after a response on the delayed lever and decreased by 1s after a response on the immediate lever. There was then a 10-day water substitution phase, or PCP withdrawal, that occurred during the mid-follicular phase (days7-11) or the late luteal phase (days24-28) of the menstrual cycle. Access to PCP and concurrent water was then restored, and the PCP withdrawal procedure was repeated over several follicular and luteal menstrual phases. PCP deliveries were higher during the luteal (vs follicular) phase. Impulsive choice was greater during the luteal (vs follicular) phase during withdrawal of the higher PCP concentration. PCP withdrawal was associated with elevated impulsive choice for SACC, especially in the luteal (vs follicular) phase of the menstrual cycle in female monkeys.

Non-Negative Matrix Factorization Based Input Function Extraction for Mouse Imaging in Small Animal PET ? Comparison with Arterial Blood Sampling and Factor Analysis

Objectives: Retrieving the accurate time-tracer activity concentration curve of the blood (arterial input function) is mandatory for performing bio kinetic model analysis of dynamic PET data. Especially in small rodents, gathering the input function remains an active area of research as no generally applicable solution was found so far. While surgically catheterizing blood vessels of rodents is possible, it is labour intensive and time resolution of blood sampling is restricted due to the limited amount of overall blood and the procedure of blood withdrawal itself. Obtaining the input function from the PET images themselves seems thus to be favourable, but suffers from several factors, one of them being spill-in of adjacent tissues. Particularly in mice and for [18F]FDG, the spill-in complicates using the time-activity curve (TAC) from a region of interest (ROI) over the left ventricle (LV) because the signal of the ROI contains contributions from both, myocardial uptake as well as arterial blood activity. We propose non-negative matrix factorization (NMF) as an image based algorithm for separating myocardial tracer concentration from the blood input function. The aim of this study was to evaluate the potential of NMF as an image based algorithm for retrieving the input function by comparison with blood sampling and Factor Analysis (FA). Method: The femoral arteries of eight mice were surgically catheterized. With the injection of [18F]FDG, a 60 minute PET scan was started during which arterial blood samples were manually drawn from the catheter. For analysis, NMF and FA were performed in a ROI placed over the LV. The NMF algorithm shares similarities with principal component analysis and FA, the advantage over the later two being its non-negativity constraint. For normalization of the NMF extracted curve, the peak value of tracer activity in an early image of the LV and a late blood sample was used. The normalized NMF curve was visually compared to the TAC retrieved from the blood samples and to the FA retrieved TAC. For a quantitative comparison of performance, Pearson correlation and square-root of sum of squares (RSS) between NMF/FA and blood sampling curves was calculated. Results: TAC based on NMF, FA and arterial blood samples were obtained and compared in all 8 mice. The NMF derived curves described the blood sampling based curves visually significantly better than FA. Pearson correlation between NMF and blood sampling curves ranged from 0.21 to 0.92 with an average of 0.69. Pearson correlation for FA ranged from 0.46 to 0.81 with an average of 0.65. Mean RSS was 2.70E + 006 for NMF and 3.40E + 006 for FA. Conclusion: In the examined parameters, visual accordance, Pearson correlation and RSS, NMF performs superior to FA and seems to be a promising method for the extraction of the input function from PET images of small rodents without the need for arterial blood sampling.

Changes in the Regulatory Base of the Budget Process in October 2013

The Government of the Russian Federation has issued documents which introduce from 2014 a simplified procedure for withdrawal of land plots from public (municipal) entities and state-owned enterprises in favor of the state treasury; amendments were introduced in to the procedure for provision of state guarantees on loans attracted by enterprises of the defense industry complex.

RASPBERRY LEAF AND BUD MITE (PHYLLOCOPTES GRACILIS) IN SERBIA: THE PEST STATUS AND CONTROL OPTIONS

The raspberry leaf and bud mite, Phyllocoptes gracilis (Nal.) is the most important secondary pest of raspberry in commercial production plantations in Serbia, which may cause significant damage to a raspberry planting if control measures are not carried out. In the past organophosphates and pyrethroids, insecticides with a wide activity spectrum and added acaricidal activity, were the main protection against this insect pest, partially resolving the issue. Besides them, endosulfan was widely used, an organochlorine substance known for its high efficacy in eriophyoid control. Nowadays, most of these substances are withdrawn from use or are facing withdrawal procedure. Except abamectin and milbemectin, insecticides recommended instead of organophosphates and other substances of older generations do not have significant activity against mites. Besides, P. Gracilis populations often reach high abundance, and after harvest in dryer years a more significant presence of two-spotted spider mite, Tetranychus urticae, is usually recorded, so acaricides have to be included in raspberry protection programs. Propargite, organotins (cyhexatin, fenbutatin-oxide), benzoylureas (flucycloxuron, flufenoxuron), and hexythiazox - acaricides of older and mid-generations still available on the market - proved to be efficient in eriophyoid control. Among acaricides commercialized in the last 15-20 years, a high activity against eriophyoids is exhibited by METI acaricides (fenazaquin, fenpyroximate, pyridaben, tebufenpyrad), diafenthiuron, chlorfenapyr, and tetronic acid derrivatives (spirodiclofen, spiromesifen). In order to improve the control of raspberry leaf and bud mite, laboratory and field research is needed with emphasis on biorational and alternative acaricides and their compatibility with the predatory mite Phytoseius macropilis Banks, which is an efficient natural regulator of P. gracilis in Serbian raspberry plantations.

Comments Regarding Practice Recommendations of the American Thyroid Association for Radiation Safety in the Treatment of Thyroid Disease with Radioiodine

The authors of the recently published ‘‘Radiation Safety in the Treatment of Patients with Thyroid Diseases by Radioiodine (I): Practice Recommendations of the American Thyroid Association’’ (1) are to be commended for creating a document that reflects the result of countless hours of literature review, survey compilation, discussion, and compromise. This study has systematically applied techniques to achieve as low as reasonably achievable (ALARA) exposure to radiation, and this represents a significant step forward in the protection of those coming in contact with individuals treated with I. It effectively communicates newer approaches to assessing the likely maximum dose to another person (usually family) that are not only based on total administered doses but also estimates of clearance and retention. For example, an individual with Graves’ disease with high radioactive iodine uptake who received 10 millicurie (mCi) of I may expose others to more radiation than someone with thyroid cancer post–total thyroidectomy, stimulated with rhTSH and ablated with 100 mCi. We have already modified our institution’s protocols by adapting some of the committee’s recommendations. However, we would like to share our concerns about some of the committee’s recommendations regarding the following. In regard to the section titled ‘‘Post-therapy living situations,’’ the recommendation about sleeping in separate beds, the committee should consider the dynamic clearance of the I as predicted by the expected pharmacokinetics of I. For example, the amount of radioiodine delivered to and retained in the thyroid gland of a patient with Graves’ disease who receives 10 mCi is often greater than the radiation exposure of someone with a multinodular goiter who is either euthyroid or only mildly hyperthyroid receiving 30 mCi. Yet, the former patient would be advised to sleep alone for 3 days, while the latter patient would be told to do so for 11 days. The section entitled ‘‘Personal hygiene’’ contains instructions on the disposal of radioactive trash that cannot be flushed or washed in a routine fashion which require several considerations. First of all, just how much contamination will there be? Highly conscientious, environmentally aware, independently living people are unlikely to generate much radioactive trash. On the other hand, a debilitated, dependent patient, who wears incontinence diapers, is quite likely to produce a significant amount of contamination. Recommendations should, therefore, be based on likely levels of contamination. For example, when considering the use of disposable versus washable utensils, we recommend using washable utensils—as opposed to disposable ones. We instruct patients to wash them separately from the family dishes whenever possible. This minimizes the amount of material that must be stored. When counseling patients about transporting radioactive trash, the recommendation states, ‘‘Bring your specified trash bag back to the treatment facility.’’ We feel that it is not feasible for many urban dwellers who are dependent on public transportation, which should not be used for this purpose, to comply with this recommendation. Further, in regard to the home storage of radioactive trash, it is recommended that, ‘‘After 80 days the bag may be removed as other trash bags.’’ We believe that holding biohazard trash for 80 days poses a hygienic risk and storage challenge for those living in small apartments in multi-unit dwellings. Seeking alternative storage options may force them to compromise their right to privacy and expose others to unnecessary radiation. We recommend landfill disposal after a shorter period for continent patients, such as 4 weeks depending on the sensitivity of local landfill detectors. Incontinent patients should be treated as inpatients. Willegaignon et al.’s (2) experience in Brazil indicates that patient home waste contamination levels were a third of the International Atomic Energy Agency (IAEA) concentration limit for release criteria. We propose that our professional societies request that the Nuclear Regulatory Commission (NRC) adopt IAEA limits as reasonable alert levels for waste site monitors. Driving an automobile while potentially impaired by the effects of hypothyroidism has led us to carefully consider our recommendations to patients undergoing thyroid hormone withdrawal procedures. We routinely instruct patients who are overtly hypothyroid not to drive. Consider, for example, the case of a school bus driver with severe hypothyroidism who caused a fatal collision, cited by Rosenthal (3). First and foremost this tragedy could have been prevented by not

Effects of imidazoline I2 receptor ligands on acute nociception in rats

This study examined the antinociceptive effects of seven imidazoline I2 receptor ligands in a rat warm water tail withdrawal procedure (46 and 50 °C). Agmatine, 2-BFI, phenyzoline, and diphenyzoline produced a significant antinociceptive activity at 46 °C. BU224, S22687, and idazoxan had no effect at 46 °C up to doses that altered the locomotor activity. None of the drugs showed antinociceptive activity at 50 °C. It is suggested that I2 receptor agonists have antinociceptive activity for acute phasic pain under weak noxious stimulus, and the effects are efficacy-dependent. These data explain the findings that I2 receptor agonists enhance the antinociceptive effects of opioids and support developing higher-efficacy I2 receptor agonists for the treatment of pain.

Interventions by Virginia's Colleges to Respond to Student Mental Health Crises

This study examined interventions by colleges in 2008-2009 to respond to students during mental health crises. Public (N=15) and private (N=25) four-year colleges and two-year community colleges (N=23) in Virginia were surveyed about academic policies governing responses to apparent mental health crises among students and how often they were invoked. Procedures used most often by public and private colleges, respectively, were parental notification (six and 25 per 10,000 students); voluntary medical withdrawal, usually linking readmission to treatment (29 and 25 per 10,000 students); mandatory treatment following disciplinary sanction (302 and 1,704 per 10,000 students); and monitoring by a campus threat assessment team (15 and 51 per 10,000 students). Procedures for involuntary hospitalization and involuntary medical withdrawal were rarely invoked. Community colleges were much less likely than four-year colleges to use any of these procedures. Most four-year colleges in Virginia, both public and private, occasionally invoke a variety of protective interventions to respond to apparent mental health crises experienced by students, but the number of students annually affected by these policies is generally small. The main value of procedures for mandated or leveraged treatment in college may be to motivate students with mental illness to seek treatment voluntarily. Aside from sporadic use of threat assessment teams in extreme instances, community colleges, which do not have counseling centers, lack the capacity to undertake these interventions.

The Founding Father and the General: David Ben-Gurion and Moshe Dayan

The Founding Father and the General: David Ben-Gurion and Moshe Dayan

Effects of imidazoline I2 receptor ligands on morphine- and tramadol-induced antinociception in rats

Currently available analgesics cannot meet the increasing clinical needs and new analgesics with better therapeutic profiles are in great demand. The imidazoline I₂ receptor is an emerging drug target for analgesics. However, few studies have examined the effects of selective I₂ receptor ligands on the antinociceptive activity of opioids. This study examined the antinociceptive effects of the opioids morphine (0.1-10 mg/kg) and tramadol (3.2-56 mg/kg), the nonselective I₂ receptor ligand agmatine (10-100 mg/kg), and the selective I₂ receptor ligands 2-(2-benzofuranyl)-2-imidazoline hydrochloride (2-BFI; 1-10 mg/kg) and 2-(4, 5-dihydroimidazol-2-yl) quinoline hydrochloride (BU224; 1-10mg/kg), alone and in combination, in a warm water tail withdrawal procedure in rats. Morphine and tramadol but not agmatine, 2-BFI or BU224 increased tail withdrawal latency in a dose-related manner at 48°C water. Agmatine and 2-BFI but not BU224 dose-dependently enhanced the antinociceptive effects of morphine and tramadol, shifting the dose-effect curves of morphine and tramadol leftward. The enhancement of agmatine and 2-BFI on morphine and tramadol antinociception was prevented by BU224. These results, combined with the fact that BU224 and 2-BFI share similar behavioral effects under other conditions, suggest that BU224 has lower efficacy than 2-BFI at I₂ receptors, and that the enhancement of opioid antinociception by I₂ receptor ligands depends on their efficacies.

A Knot of the Central Catheter Created During Usage Period

The use of central veins catheters for diagnostic and therapeutic purposes is a common procedure in intensive care unit (ICU) and operating rooms. This procedure, even if performed by skillful hands, might cause complications during the insertion maneuvre or in the course of use. Preventing and decreasing the rate of the complications requires a correct technique application, from the insertion to the withdrawal procedure of the catheter. We are describing a rare complication case, which occurred a few days after the insertion of the catheter. The mechanisms of the presented complication must be rare, but is potentially possible. doi:10.4021/jmc211w

Prednisolone and Budesonide for Short- and Long-Term Treatment of Microscopic Colitis: Systematic Review and Meta-analysis

The incidence of microscopic colitis and its disease burden are increasing, yet there is limited systematic information addressing the use of conventional corticosteroids and budesonide in microscopic colitis. We performed a systematic review and meta-analysis on the short- and long-term efficacy of corticosteroids in treatment of microscopic colitis. Randomized controlled trials that met predetermined selection criteria were included. Articles were identified through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, proceedings of major gastroenterology meetings, and reference lists of trials and review articles. Eight randomized trials were identified. A total of 248 patients were randomized to corticosteroid versus placebo. The intervention was budesonide in 7 trials and prednisolone in 1 trial. Budesonide was significantly more effective than placebo for short-term clinical response (risk ratio [RR], 3.07; 95% confidence interval [CI], 2.06-4.57) and long-term clinical response (RR, 3.22; 95% CI, 1.05-9.89). Prednisolone was not superior to placebo for short-term clinical response (RR, 2.00; 95% CI, 0.38-10.58). Histologic improvement was seen with both short- and long-term budesonide (RR, 3.76; 95% CI, 2.00-7.06, and RR, 2.50; 95% CI, 1.25-4.98, respectively). Symptom relapse occurred in 46%-80% of patients within 6 months of treatment cessation. Withdrawal because of adverse effects occurred in 4.4% of patients, with no difference between study groups (P = .55). Both short- and long-term treatment with budesonide is effective and well-tolerated for microscopic colitis. However, the rate of symptom relapse once budesonide is discontinued is high. Further studies are needed to determine optimal treatment duration, dose, and withdrawal procedure.

Study on continuous casting of bulk metallic glass

Continuous casting method for massive production of steel, aluminum, copper or other crystalline alloy ingot is a very important industrial technology for its low energy consumption and high productivity. In this study, a new continuous casting method was developed for the massive production of bulk metallic glass ingot with centimeter-scale diameter without length limitation. An intermittent withdrawal procedure was practiced for continuous casting of bulk glassy alloy. The new developed continuous casting method can provide a cooling speed as high as that provided by the stationary mold casting method. A Zr-based glassy alloy rod with a diameter of about 10 mm and length of tens of centimeters was prepared by the continuous casting method for the first time.

The water method significantly enhances detection of diminutive lesions (adenoma and hyperplastic polyp combined) in the proximal colon in screening colonoscopy: Data derived from two RCT in US veterans

PURPOSE: Emerging data indicate a colonoscopist-controlled method is needed to avoid missing proximal colon pre-malignant lesions. Screening colonoscopy does not prevent all proximal colon cancers. Even diminutive lesions in the proximal colon harbor dysplasia. In addition to adenomas (presumptive cancer precursors), recent proposals to reevaluate proximal colon hyperplastic polyps as serrated polyps which could be pre-malignant or harbingers of interval neoplasia dramatize the importance of attending to these lesions. The finding that the water method increased yield of proximal diminutive adenomas prompted assessment of the hypothesis that the water method increases yield of all proximal diminutive lesions (adenoma and hyperplastic polyp) in screening cases. METHODS: Two RCT assessed the water method with primary outcome of completion of unsedated colonoscopy when the option of scheduled, unsedated or sedation on demand was used. Diminutive (<10 mm) lesions proximal to the splenic flexure were tracked. RESULTS: In screening cases, 31% and 6% of the water and air group had at least one proximal diminutive lesion (p=0.0012). Regression analysis revealed withdrawal time, method and volume of water used were significant predictors of proximal diminutive lesions. Effect of the water method on detection of proximal diminutive lesions was independent of age, body mass index, endoscopist, sedation, cecal intubation rate, bowel cleanliness score on withdrawal and total procedure time. LIMITATION: Male subject predominance, analysis of secondary outcomes of pooled RCT data. CONCLUSION: The hypothesis that the water method effectively enhances proximal diminutive lesion detection in screening colonoscopy in diverse clinical settings should be tested.