Impact of Bariatric Surgery on the Pharmacokinetics Parameters of Amoxicillin The effect of bariatric surgery on the direct oral anticoagulant rivaroxaban: the extension study. Spine surgery research: on and beyond current strategies. Pharmacokinetics of Amoxicillin: Dose Dependence After Intravenous, Oral, and Intramuscular Administration European Respiratory Society guidelines for the management of adult bronchiectasis Pharmacokinetics and pharmacodynamics of single doses of rivaroxaban in obese patients prior to and after bariatric surgery Exercise for people with cancer: a clinical practice guideline. Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic exposure of CYP3A4 and P-glycoprotein substrates. Eccentric exercise training in chronic mid-portion Achilles tendinopathy: a systematic review on different protocols. Implant loading protocols for the partially edentulous posterior mandible. Methodology and reporting of randomised controlled trials. Pharmacokinetics of orally administered melatonin in critically ill patients. Interventions aimed at increasing research use in nursing: a systematic review Caries-preventive effect of glass ionomer and resin-based fissure sealants on permanent teeth: An update of systematic review evidence Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol Pharmacokinetics of Zanamivir After Intravenous, Oral, Inhaled or Intranasal Administration to Healthy Volunteers Population Pharmacokinetics of Oral Topotecan in Infants and Very Young Children with Brain Tumors Demonstrates a Role of ABCG2 rs4148157 on the Absorption Rate Constant From the Editors’ Desk: Bias in Systematic Reviews—Let the Reader Beware Evaluation of the pharmacokinetic profile and analgesic efficacy of oral morphine after total hip arthroplasty Development of a core outcome set for clinical trials in inflammatory bowel disease: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey Effectiveness of exercise interventions on physical function in community-dwelling frail older people: an umbrella review of systematic reviews Improving the reporting of randomised trials: the CONSORT Statement and beyond. Variation in bowel preparation among pediatric surgeons for elective colorectal surgery: A problem of equipoise or a knowledge gap of the available clinical evidence?
Background Bariatric surgery leads to several anatomo-physiological modifications that may affect pharmacokinetic parameters and consequently alter the therapeutic effect of drugs , such as antibiotics . The pharmacokinetics of oral amoxicillin after Roux-en-Y gastric bypass ( RYGB ) surgery is unknown . Objectives The objective of this study was to evaluate the impact of bariatric surgery on the pharmacokinetics of  amoxicillin . Methods This study was performed as a r and omized , open-label , single-dose clinical trial , with two periods of treatment , in which obese subjects ( n = 8) received an amoxicillin 500 mg capsule orally before and 2 months after the RYGB surgery . The  amoxicillin plasma concentration was determined by liquid chromatography coupled to mass spectrometry ( LC-MS/MS ) . Results After the surgery , the mean weight loss was 17.03 ± 5.51 kg , and mean body mass index ( BMI ) decreased from 46.21 ± 2.82 to 38.82 ± 3.32 kg/m2 . The mean amoxicillin area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration ( AUC0–tlast ) increased significantly ( 3.5-fold ) ; the maximum plasma concentration ( Cmax ) increased 2.8-fold after the bariatric surgery . No correlation was found between amoxicillin absorption , BMI , and weight loss percentage . Conclusion The alterations observed in the amoxicillin pharmacokinetics suggest that obese subjects included in this trial had a substantially increase in amoxicillin systemic exposure after RYGB surgery . However , despite this increase , its exposure was lower than the values reported for non-obese volunteers . Trial Registration Identifiers : BACKGROUND Thromboembolic disease is a potentially serious complication in bariatric surgery patients . Direct oral anticoagulants ( DOAC ) have been investigated in orthopedic surgery patients .  DOAC data after bariatric surgery are still limited to the early postsurgical period . Whether postsurgical midterm adaptations due to anatomic and physiologic alterations influence drug pharmacology is currently not known . OBJECTIVE The aim of this study was to investigate the influence of weight loss and type of bariatric surgery on midterm postsurgical pharmacokinetic and pharmacodynamic parameters of rivaroxaban . SETTING University hospital . METHODS In this monocentric study , bariatric patients received a single oral dose of rivaroxaban ( 10 mg ) 6 to 8 months after sleeve gastrectomy ( SG ) or Roux-en-Y-gastric bypass ( RYGB ) . Pharmacokinetic and pharmacodynamic parameters were assessed and compared with prebariatric surgery results . RESULTS We included 6 RYGB and 6 SG patients .  Percent excess weight loss was 71.4 % ( interquartile range 56.4 , 87.9 ) in the SG group and 76.6 % ( 64.5 , 85.7 ) in the RYGB group . Rivaroxaban mean areas under the curve 6 to 8 months after the bariatric procedure ( 922.4 µg × h/L , coefficient of variation 43.2 ) were comparable to those measured preoperatively ( 952.6 µg × h/L , 16.8 ) . There was no relevant difference between the 2 surgical procedure groups . Rivaroxaban led to a decrease of prothrombin fragments F1 + 2 over 12 hours after oral intake confirming in vivo efficacy . CONCLUSIONS Significant weight loss and altered anatomy after RYGB and SG procedures do not appear to affect the pharmacokinetics and pharmacodynamics of prophylactic rivaroxaban . A single dose of Rivaroxaban was well tolerated and considered safe in this trial BACKGROUND CONTEXT Systematic review s of the literature are powerful tools in evidence -based medicine . However , the design and report of systematic review s in spinal surgery contain many aspects amenable to improvement . PURPOSE To discuss the issues especially relevant for systematic review s in spinal surgery . METHODS From our experience of systematic review s and meta-analyses of clinical trials in  spinal surgery  , we infer guidance for the design and execution of systematic literature review s. RESULTS There are many difficulties associated with the design as well as conduct of clinical trials and consequently appraising evidence in spinal surgery . New treatments should be compared with the gold st and ard before other comparisons are investigated . Studies should present data as thoroughly as possible regarding all subgroups and follow-up moments , possibly in supplementary material . To provide the highest level of evidence , systematic review s should be as rigorously design ed as possible . CONCLUSIONS Gathering information on clinical effectiveness in spinal surgery can be improved both at the clinical study level and at the systematic review level . Alternatives to r and omized controlled trials such as comparative studies can be valuable tools on the clinical effectiveness of treatments in spinal surgery . The experience reflected in this article can support the scientific efforts in this field Amoxicillin was studied in normal subjects after intravenous , oral , and intramuscular administration of 250- , 500- , and 1,000-mg doses .  Serum drug levels were analyzed using a two-compartment open model , as well as area under the curve ( AUC ) and urinary recovery . The variations of these pharmacokinetic parameters were then examined using the three-way analysis of variance and linear regression equations . These results confirmed nearly complete oral absorption : AUC was 93 % of intravenous absorption , and urinary recovery was 86 % . The intramuscular administration of amoxicillin results in complete and reliable absorption with peak drug levels , AUCs , and urinary recovery equivalent to oral dosage . The absorption of lyophilized amoxicillin after intramuscular injection result ed in an AUC that was 92 % of intravenous absorption and urinary recovery of 91 % . The peak serum levels , time to peak , and other pharmacokinetic parameters for intramuscular injection were nearly identical to those for oral administration . Kinetics of both intramuscular and oral administration exhibited dose-dependent absorption ( absorption rate constant , 1.3/h for 250 mg and 0.7/h for 1,000 mg ) . This result ed in relatively later and lower peak serum levels for increasing dose . Total absorption , however , showed no dose dependence , as indicated by urinary recovery and AUC , which changed by less than 10 % Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients . There have been no previous international guidelines . The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature . A multidisciplinary group representing respiratory medicine , microbiology , physiotherapy , thoracic surgery , primary care , methodology and patients considered the most relevant clinical questions ( for both clinicians and patients ) related to management of bronchiectasis . Nine key clinical questions were generated and a systematic review was conducted to identify published systematic review s , r and omised clinical trials and observational studies that answered these questions . We used the GRADE approach to define the quality of the evidence and the level of recommendations . The result ing guideline addresses the investigation of underlying causes of bronchiectasis , treatment of exacerbations , pathogen eradication , long term antibiotic treatment , anti-inflammatories , mucoactive drugs , bronchodilators , surgical treatment and respiratory physiotherapy . These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes . The publication of the first ERS guidelines for bronchiectasis AIMS Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery . Studies of direct oral anticoagulants ( DOACs ) are not available in this surgical field . The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic ( PK/PD ) parameters of rivaroxaban in bariatric patients . METHODS In this single-centre study , obese patients received single oral doses of rivaroxaban ( 10 mg ) 1 day prior to and 3 days after bariatric surgery . PK and PD parameters were assessed at baseline and during 24 h after drug ingestion . RESULTS Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study .  Mean rivaroxaban area under plasma concentration-time curve , peak plasma concentration , time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1 ( coefficient of variation : 10.6 ) , 135.3 μg l-1 ( 26.7 ) , 1.5 h and 13.1 h ( 34.1 ) prior to and 1165.8 ( 21.9 ) , 170.0 ( 15.9 ) , 1.5 and 8.9 ( 44.6 ) postsurgery for SG patients and 933.7 μg·h l-1 ( 22.3 ) , 136.5 μg l-1 ( 10.7 ) , 1.5 h und 13.8 h ( 46.6 ) prior to and 1029.4 ( 7.4 ) , 110.8 ( 31.8 ) , 2.5 and 15 ( 60.0 ) postsurgery for Roux-en-Y gastric bypass patients , respectively . Prothrombin fragments ( F1 + 2 ) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting . Thrombin-antithrombin complexes dropped within 1 - 3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose  . Rivaroxaban was well tolerated and no relevant safety issues were observed . CONCLUSIONS Bariatric surgery does not appear to alter PK of rivaroxaban in a clinical ly relevant way . Effective prophylactic postbariatric anticoagulation is supported by changes in PD BACKGROUND Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group , a group organized by Cancer Care Ontario 's Program in Evidence -Based Care ( pebc ) . The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer , focusing on the benefits of specific types of exercise , recommendations about screening requirements for new referrals , and safety concerns . METHODS Consistent with the pebc 's st and ardized approach , a systematic search was conducted for existing guidelines , and systematic literature search es were performed in medline and embase for both systematic review s and primary literature . Content and methodology experts performed an internal review , which was followed by an external review by targeted experts and intended users . RESULTS The search identified three guidelines , eighteen systematic review s , and twenty-nine r and omized controlled trials with relevance to the topic . The present guideline provides recommendations for the duration , frequency , and intensity of exercise appropriate for people living with cancer . It also provides recommendations for pre-exercise assessment , safety concerns , and delivery models . CONCLUSIONS There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment , and that it does not cause harm . The present guideline is intended to support the Canadian Society for Exercise Physiology 's Canadian physical activity guidelines . The recommendations are intended for clinicians and institutions treating cancer patients in Ontario , and for policymakers and program planners involved in the delivery of exercise programs for cancer patients STUDY OBJECTIVES To evaluate the effect of  Roux-en-Y gastric bypass surgery ( RYGB ) on the pharmacokinetics of midazolam ( a CYP3A4 substrate ) and digoxin ( a P-glycoprotein substrate ) . DESIGN Prospect i ve , nonblinded , longitudinal , single-dose pharmacokinetic study in three phases : presurgery baseline and postoperative assessment s at 3 and 12 months . PATIENTS Twelve obese patients meeting current st and ards for bariatric surgery . MEASUREMENTS AND MAIN RESULTS At each study visit , patients received a single dose of oral digoxin and midazolam at 8 a.m. Blood sample s were collected at regular intervals for 24 hours after dosing . Continuous 12-lead electrocardiogram ( EKG ) , heart rate , blood pressure , and respiratory rate were monitored , and pharmacokinetic parameters from the three visits were compared . The peak plasma concentration ( Cmax ) of midazolam increased by 66 % and 71 % at 3- and 12-month post-RYGB ( p=0.017 and p=0.001 , respectively ) , whereas the median time to peak concentration ( Tmax ) was reduced by 50 % . The mean Cmax for 1'-hydroxymidazolam increased by 87 % and 80 % at 3 and 12 months ( p=0.001 and p<0.001 , respectively ) . However , neither the area under the concentration-time curve ( AUC ) for midazolam nor the metabolite-to-parent AUC ratio changed significantly over time . For digoxin , the median Tmax decreased from 40 minutes at baseline to 30 and 20 minutes at 3 and 12 months , respectively . The mean AUC for digoxin , heart rate , and EKG patterns were similar across the three study phases . CONCLUSION Contemporary proximal RYGB increases the rate of drug absorption without significantly changing the overall exposure to midazolam and digoxin . The Cmax of a CYP3A4 substrate with a high extraction ratio was substantially increased after RYGB Although eccentric exercise training has shown favorable results in chronic mid-portion Achilles tendinopathy , the optimum dosage remains unknown . A systematic review of the literature was performed in accordance with the PRISMA guidelines , in order to describe different exercise protocol s and to determine the most effective training parameters . An extensive search in MEDLINE , EMBASE , CINAHL , and CENTRAL revealed 14 r and omized and clinical controlled trials . Strong evidence was found for the Alfredson exercise protocol . In this 12-week protocol , exercises are performed 3 × 15 repetitions twice daily , both with a straight and bent knee . Exercises are performed at slow speed , and load is increased when exercises are without pain . Strong evidence was also found for gradual onset of exercises during the first week of the Alfredson program , but no uniformity of protocol s exists . Other exercise protocol s did achieve similar results , but many studies had some method ological shortcomings or lacked a detailed description of their training parameters . Because of the heterogeneity of study population s and outcome measures , and lack of reporting of training compliance data , a definitive conclusion regarding the most effective training parameters could not be made . Further research comparing the content of different exercise protocol s is warranted PURPOSE To evaluate the predictability of early and immediate loading protocol s of  implants in the posterior m and ible and to investigate whether there is a difference in success rates , survival rates , and peri-implant parameters , including marginal bone level changes , between loading protocol s. MATERIAL S AND METHODS A comprehensive systematic review of the literature was conducted . The selection of publications reporting on human clinical studies was based on predetermined inclusion criteria and was agreed upon by two review ers . RESULTS A total of 19 papers were selected : 8 on early loading , 9 addressing immediate loading , and 2 comparing immediate and early loading . Of the 19 studies , 5 were r and omized clinical trials and 14 were prospect i ve studies . CONCLUSIONS Existing literature supports the early loading of  microroughened dental implants in the partially edentulous posterior m and ible at 6 to 8 weeks in the absence of modifying factors . Therefore , loading within this time frame can be considered routine for the majority of clinical situations in the posterior m and ible , either with single crowns or fixed dental prostheses . Immediate loading of microroughened dental implants in the partially edentulous posterior m and ible proved to be a viable treatment alternative . Caution is necessary when interpreting published outcomes for immediate loading , as the inclusion exclusion criteria are inconsistent and many subjective confounding factors are evident . Additional studies with longer follow-ups , specifically r and omized clinical trials , are needed to consoli date the data for immediate loading . Priority should be given to trials testing immediate loading A systematic review of the literature will fail to provide information needed for evidence -based medicine ( EBM ) if the design , execution and reporting of individual trials do not adhere to strict guidelines . Experience gained while conducting systematic literature review s have revealed serious shortcomings in current literature . These limitations pertain to r and omisation , blinding , outcome assessment s and data reporting . The principles related to these issues are discussed with solutions and improvements provided Critically ill patients exhibit reduced  melatonin secretion , both in nocturnal peaks and basal daytime levels . Oral melatonin supplementation may be useful for known sedative and antioxidant properties . Its early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospect i ve trial . During their third and fourth Intensive Care Unit ( ICU ) day , they underwent two different sets of repeated blood sample s to detect serum melatonin levels through radio-immuno-assay . Cohort 1 : sample s taken at 20:00 , 20:45 , 21:30 , 24:00 , 03:00 , 06:00 , 14:00 , 20:00 to describe the daily pharmacokinetics . Cohort 2 : 20:00 , 20:05 , 20:10 , 20:20 , 20:30 , 20:45 to study the early absorption . On ICU day 3 , endogenous levels were measured , while the absorption of exogenous melatonin  was determined on ICU day 4 after administration , at 20:00 , of 3 mg melatonin . All basal levels were below the expected values . Following enteral administration , pharmacological levels were already reached in 5 min , with a serum peak after 16 min ( half-absorption time : 3 min 17 s ) . The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min . Serum melatonin levels decreased significantly after midnight ; pharmacological levels were maintained up to 10 hr following administration . No excessive sleepiness was reported in this patient group . Critically ill patients exhibited reduced melatonin secretion , as reported in the literature . Despite the critical illness , the oral bioavailability was satisfactory : serum levels after oral administration showed basically unchanged intestinal absorption , while disappearance rate was slower than reported elsewhere in healthy volunteers Background There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians . However , most work has focused on medical practice s ; and nursing is not well represented in existing systematic review s. The purpose of this article is to report findings from a systematic review of interventions aim ed at increasing research use in nursing . Objective To assess the evidence on interventions aim ed at increasing research use in nursing . Methods A systematic review of research use in nursing was conducted using data bases ( Medline , CINAHL , Healthstar , ERIC , Cochrane Central Register of Controlled Trials , and Psychinfo ) , grey literature , ancestry search ing ( Cochrane Data base of Systematic Review s ) , key informants , and manual search ing of journals . R and omized controlled trials and controlled before- and after- studies were included if they included nurses , if the intervention was explicitly aim ed at increasing research use or evidence -based practice , and if there was an explicit outcome to research use . Method ological quality was assessed using pre-existing tools . Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy . Results Over 8,000 titles were screened . Three r and omized controlled trials and one controlled before- and after- study met the inclusion criteria . The method ological quality of included studies was generally low . Three investigators evaluated single interventions . The most common intervention was education . Investigators measured research use using a combination of surveys ( three studies ) and compliance with guidelines ( one study ) . Research er-led educational meetings were ineffective in two studies . Educational meetings led by a local opinion leader ( one study ) and the formation of multidisciplinary committees ( one study ) were both effective at increasing research use . Conclusion Little is known about how to increase research use in nursing , and the evidence to support or refute specific interventions is inconclusive . To advance the field , we recommend that investigators : ( 1 ) use theoretically informed interventions to increase research use , ( 2 ) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use , as well as , measuring patient outcomes relevant to the intervention , and ( 3 ) use more robust and method ologically sound study design s to evaluate interventions . If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use Background This article constitutes a partial up date of the original systematic review evidence by Yengopal et al. from 15 January 2008 ( published in the Journal of Oral Science in 2009 ) with primary focus on research quality in regard to bias risk in trials . Its aim is to up date the existing systematic review evidence from the English literature as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same . Methods In addition to the 12 trials included during the original systematic review , 5 new trials were identified during the data base search ( up to 26 August 2010 ) and 2 further trials were included from a h and search and reference check . Of these , 3 trials were excluded and 16 were accepted for data extraction and quality assessment . The quality of accepted trials was assessed , using up date d quality criteria , and the risk of bias was investigated in more depth than previously reported . In addition , the focus of quantitative synthesis was shifted to single data sets that were extracted from the accepted trials . Results Twenty-six dichotomous and 4 continuous data sets were extracted . Meta- analysis and cumulative meta- analysis were used in combining clinical ly homogenous data sets . The overall outcome of the computed data sets suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants . Conclusions This overall outcome is in agreement with the conclusions of the original systematic review . Although the findings of the trials identified in this up date may be considered to be less affected by attrition- and publication bias , their risk of selection - and detection-/performance bias is high . Thus , verification of the currently available results requires further high quality r and omised control trials Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide . Most chronic diseases are associated with underlying preventable risk factors , such as elevated blood pressure , high blood glucose or glucose intolerance , high lipid levels , physical inactivity , excessive sedentary behaviours , and overweight/obesity . The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood . Sugar-sweetened beverages are known to be significant sources of additional caloric intake , and given recent attention to their contribution in the development of chronic diseases , a systematic review is warranted . We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are . Methods / Design Of interest are studies addressing sugar-sweetened beverage consumption , taking a broad perspective . Both direct consumption studies as well as those evaluating interventions that influence consumption ( e.g. school policy , educational ) will be relevant . Non-specific or multi-faceted behavioural , educational , or policy interventions may also be included subject to the level of evidence that exists for the other interventions /exposures . Comparisons of interest and endpoints of interest are pre-specified . We will include r and omized controlled trials , controlled clinical trials , interrupted time series studies , controlled before-after studies , prospect i ve and retrospective comparative cohort studies , case – control studies , and nested case – control design s. The MEDLINE ® , Embase , The Cochrane Library , CINAHL , ERIC , and PsycINFO ® data bases and grey literature sources will be search ed . The processes for selecting studies , abstract ing data , and resolving conflicts are described . We will assess risk of bias using design -specific tools . To determine sets of confounding variables that should be adjusted for , we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessment s. Meta- analysis will be conducted where appropriate ; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach will be used to determine the quality of evidence for outcomes . Systematic review registration PROSPERO CRD42014009641 Objective The objective of these studies was to examine the clinical pharmacokinetics and safety of zanamivir , an influenza A and B virus neuraminidase inhibitor , when administered to healthy volunteers . Design The safety , tolerability and pharmacokinetics of zanamivir administered by a number of routes were assessed in r and omised , double-blind and placebo-controlled studies . The study of absolute oral bioavailability had an open design . Study participants The participants in these studies were healthy male or female volunteers . Interventions Zanamivir was administered as single or multiple doses by the intravenous , oral , inhaled ( nebuliser and dry powder ) and intranasal routes . Serum and urine sample s were obtained for determination of pharmacokinetic parameters , and nasal washes and throat gargles were performed to assess drug concentrations in the nose and throat . Safety was evaluated by monitoring adverse events , vital signs and laboratory parameters . Results Zanamivir was well tolerated at all doses by all routes ; no serious adverse events were reported . The kinetics of zanamivir were linear with single intravenous doses up to 600 mg , and there was no evidence of modification in the kinetics after repeated twice-daily administration . Approximately 90 % of zanamivir was excreted unchanged in the urine . The elimination of zanamivir from the serum was a first-order process with a half-life of approximately 2 hours and , at 16L , the volume of distribution was similar to that of extracellular water . The absolute oral bioavailability of  zanamivir was low , averaging 2 % . After intranasal or oral inhaled administration , a median of 10 to 20 % of the dose was systemically absorbed , with maximum serum concentrations generally reached within 1 to 2 hours . The median serum half-life ranged between 2.5 and 5.05 hours , suggesting that the elimination rate is limited by absorption . There was no evidence of modification in the kinetics after repeated inhaled administration . Conclusions Zanamivir is a well tolerated drug . The low level of absorption of the drug after inhaled administration results in low serum concentrations , and therefore there is modest systemic exposure to zanamivir after inhalation . Zanamivir is not metabolised , and the potential for clinical ly relevant drug-drug interactions is very low For infants and very young children with brain tumors , chemotherapy after surgical resection is the main treatment due to neurologic and neuroendocrine adverse effects from whole brain irradiation . Topotecan , an anticancer drug with antitumor activity against pediatric brain tumors , can be given intravenous or orally . However , high interpatient variability in oral drug bioavailability is common in children less than 3 years old . Therefore , this study aim ed to determine the population pharmacokinetics of  oral topotecan in infants and very young children , specifically evaluating the effects of age and ABCG2 and ABCB1 on the absorption rate constant ( Ka ) , as well as other covariate effects on all pharmacokinetic parameters . A nonlinear mixed effects model was implemented in Monolix 4.3.2 ( Lixoft , Orsay , France ) . A one-compartment model with first-order input and first-order elimination was found to adequately characterize topotecan lactone concentrations with population estimates as [ mean ( S.E. ) ] ; Ka = 0.61 ( 0.11 ) h−1 , apparent volume of distribution ( V/F ) = 40.2 ( 7.0 ) l , and apparent clearance ( CL/F ) = 40.0 ( 2.9 ) l/h . After including the body surface area in the V/F and CL/F as a power model centered on the population median , the ABCG2 rs4148157 allele was found to play a significant role in the value of Ka . Patients homozygous or heterozygous for G > A demonstrated a Ka value 2-fold higher than their GG counterparts , complemented with a 2-fold higher maximal concentration as well . These results demonstrate a possible role for the ABCG2 rs4148157 allele in the pharmacokinetics of oral topotecan in infants and very young children , and warrants further investigation S ystematic review s are relied upon by clinicians and policymakers as high- quality evidence for decision-making . In some hierarchies of evidence quality , systematic review s are ranked at the top , higher than r and omized controlled trials . A properly conducted systematic review that is based on high- quality articles provides very strong evidence ; policymakers recognize this value and solicit many such review s. Busy clinicians rely on well-executed systematic review s to quickly synthesize the literature and guide them in managing patients . However , there are important inherent weaknesses that can limit the quality of systematic review s and can lead to erroneous conclusions . Consumers of systematic review s should approach them with a healthy sense of skepticism . Unfortunately , many of these weaknesses may not be obvious to the various stakeholders who routinely invest their trust in such review s. The first bias one encounters is inherent in the research enterprise . Generally , research ers design studies to demonstrate maximum effect ; hence they are careful about the population selected , the interventions tested , and the outcomes assessed . For example , interventions are often tested in population s that are at high risk for experiencing the outcome in question and are likely to respond to the intervention . Not only can this make results difficult to generalize , but it often results in studies that overstate the benefit ; subsequent studies frequently find less benefit . This is particularly common when the pool of available studies consists of small , single-center investigations , trials that are particularly likely to show large effects . While usually not intentional , the combination of careful selection of population and outcomes can distort clinical research and obscure truth . This inherent bias in the research enterprise can not be fixed ; however , if there are a sufficient number of studies , conducted across different setting s and population s , this problem can be partially ameliorated with systematic review s. Systematic review s are vulnerable to a number of biases . First , the question may not be well-defined . A marker of a high- quality systematic review is the inclusion of a purpose statement in which the specific research question is clearly articulated . Specificity is key : what are they willing to accept as evidence , what population , what intervention , what duration , what doses , what outcomes and when ? Second , the search strategy should be broad enough to reassure readers that no studies were left out . Research ers commonly limit their search to English- language articles . However , there is no difference between the quality of articles in English and those in other language s , and limiting the search to English-only should be a red flag to readers . The bibliographies of retrieved articles should also be review ed . All search strategies should include input from an experienced medical librarian . Third , the quality of included articles must be carefully assessed . The higher the quality of articles that provide the bulk of the systematic review ’s conclusions , the more confident readers can be in those conclusions . Readers should be wary of review s that are based on observational data or uncontrolled clinical trials . A statistical package will analyze whatever data the analyst feeds it , and will provide an estimate of an overall effect and a 95 % confidence interval . This can mislead readers into believing that our underst and ing of the effect is more concrete than it is . Pooling of observational data can lead to answers that differ material ly from the results of r and omized controlled trials . Readers should also be wary of systematic review s built on low sample numbers , either few studies or small sample s within each study . The number of studies necessary to produce believable results is an area of ongoing debate . A recent article discussed the benefits of  Trial Sequential Analysis ( TSA )  , a method that allows metaanalysts to determine the likelihood that the review contains either a type I error ( finding a difference that does not exist ) or a type II error ( reporting no difference when in fact one exists ) . TSA theory is similar to the principles governing stopping rules for interventional trials . It takes the total sample size and the size of the effect , and establishes boundaries . These boundaries provide confidence that the sample size is large enough to avoid type I or II errors . We strongly recommend routinely including them in meta-analyses . Fourth , very careful attention must be paid to the issue of publication bias . Most readers recognize that studies with nonsignificant results face greater publication hurdles . This is a wellrecognized phenomenon ; protocol s with non-significant results are both less likely to be published and , when published , more likely to encounter significant delays than studies with significant Published online December 12 , Background and objective : Oral morphine may be useful for postoperative pain relief , but few studies have tested its use after in‐hospital surgery . Methods : We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty . We recruited 60 patients who had total hip arthroplasty under general anaesthesia . The patients were r and omized to receive placebo , 10 mg morphine sulphate or 20 mg morphine sulphate orally every 4 h for 24 h. The oral administration was started 3 h after the morphine‐loading dose in the Post Anaesthesia Care Unit and then patients used intravenous morphine patient‐controlled analgesia for 24 h. Pain score at rest ( scored by patients on a visual analogue scale ) , sedation , nausea , vomiting and urinary retention were monitored . In 11 additional total hip arthroplasty patients , we determined the pharmacokinetics of morphine and its metabolites after oral administration of 20 mg morphine sulphate every 4 h for 16 h. Results : The amount of morphine administered via patient‐controlled analgesia over 24 h was reduced in the 20‐mg group compared with that in the placebo group ( 19.0 ± 2.7 mg vs. 33.0 ± 5.5 mg ; P = 0.03 ) . No significant morphine‐sparing effect was observed in the 10‐mg group . Pain scores and side‐effects were similar in all groups . The pharmacokinetic study revealed a limited and slow absorption of morphine . Conclusion : Despite a limited absorption of oral morphine postoperatively , high doses of oral morphine have a significant analgesic effect after total hip arthroplasty Introduction Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) , the main forms of inflammatory bowel disease ( IBD ) , are chronic , progressive and disabling disorders of the gastrointestinal tract . Although data from r and omised controlled trials ( RCTs ) provide the foundation of evidence that vali date s medical therapy for IBD , considerable heterogeneity exists in the measured outcomes used in these studies . Furthermore , in recent years , there has been a paradigm shift in IBD treatment targets , moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance , inflammatory biomarkers and histological and radiographic end points . The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development . Accordingly , there exists a need to harmonise measures used in clinical trials through the development of a core outcome set ( COS ) . Methods and analysis The development of an IBD-specific COS includes four steps . First , a systematic literature review is performed to identify outcomes previously used in IBD RCTs . Second , semistructured qualitative interviews are conducted with key stakeholders , including patients , clinicians , research ers , pharmaceutical industry representatives , healthcare payers and regulators to identify additional outcomes of importance . Using the outcomes generated from literature review and stakeholder interviews , an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS . Finally , a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials . Ethics and dissemination Given that over 30 novel therapeutic compounds are in development for IBD treatment , the design of robust clinical trials measuring relevant and st and ardised outcomes is crucial . St and ardising outcomes through a COS will reduce heterogeneity in trial reporting , facilitate valid comparisons of new therapies and improve clinical trial quality Objectives : This umbrella review aim ed to determine the effectiveness of exercise interventions , alone or in combination with other interventions , in improving physical function in community-dwelling older people identified as pre-frail or frail . Introduction : Exercise is said to have a positive impact on muscle mass and strength which improves physical function and hence is beneficial for the treatment of frailty . Several systematic review s discuss the effects of exercise interventions on physical function parameters , such as strength , mobility , gait , balance and physical performance , and indicate that multi-component exercise , including resistance , aerobic , balance and flexibility training , appears to be the best way in which to improve physical function parameters in frail older people . However , there is still uncertainty as to which exercise characteristics ( type , frequency , intensity , duration and combinations ) are the most effective and sustainable over the long-term . Inclusion criteria : Participants were adults , 60 years or over , living in the community and identified as pre-frail or frail . Quantitative systematic review s , with or without meta- analysis that examined the effectiveness of exercise interventions of any form , duration , frequency and intensity , alone or in combination with other interventions design ed to alter physical function parameters in frail older people , were considered . The quantitative outcome measures were physical function , including muscular strength , gait , balance , mobility and physical performance . Methods : An iterative search strategy for ten bibliometric data bases and gray literature was developed . Critical appraisal of seven systematic review s was conducted independently by two review ers using a st and ard Joanna Briggs Institute tool . Data was extracted independently by two review ers using a st and ard Joanna Briggs Institute data extraction tool and summarized using a narrative synthesis approach . Results : Seven systematic review s were included in this umbrella review , with a total of 58 relevant r and omized controlled trials and 6927 participants . Five systematic review s examined the effects of exercise only , while two systematic review s reported on exercise in combination with a nutritional approach , including protein supplementations , as well as fruit and dairy products . The average  exercise frequency was 2–3 times per week ( mean 3.0 ± 1.5 times per week ; range 1–7 weekly ) for 10–90 minutes per session ( mean of 52.0 ± 16.5 mins ) and a total duration of 5–72 weeks with the majority lasting a minimum of 2.5 months ( mean 22.7 ± 17.7 weeks ) . Multi-component exercise interventions can currently be recommended for pre-frail and frail older adults to improve muscular strength , gait speed , balance and physical performance , including resistance , aerobic , balance and flexibility tasks . Resistance training alone also appeared to be beneficial , in particular for improving muscular strength , gait speed and physical performance . Other types of exercise were not sufficiently studied and their effectiveness is yet to be established . Conclusions : Interventions for pre-frail and frail older adults should include multi-component exercises , including in particular resistance training , as well as aerobic , balance and flexibility tasks . Future research should adopt a consistent definition of frailty and investigate the effects of other types of exercise alone or in combination with nutritional interventions so that more specific recommendations can be made An extensive and growing number of review s of the published literature demonstrate that health research publications have frequent deficiencies . Of particular concern are poor reports of r and omised trials , which make it difficult or impossible for readers to assess how the research was conducted , to evaluate the reliability of the findings , or to place them in the context of existing research evidence . As a result , published reports of trials often can not be used by clinicians to inform patient care or to inform public health policy , and the data can not be included in systematic review s. Reporting guidelines are design ed to identify the key information that research ers should include in a report of their research . We describe the history of reporting guidelines for r and omised trials culminating in the CONSORT Statement in 1996 . We detail the subsequent development and extension of CONSORT and consider related initiatives aim ed at improving the reliability of the medical research literature PURPOSE Despite rigorous data from adult literature demonstrating that oral antibiotics ( OA ) reduce infectious complications and mechanical bowel preparation ( MBP ) alone does not , MBP alone remains the preferred approach among pediatric surgeons . We aim ed to explore the nature of this discrepancy through a survey of the American Pediatric Surgical Association membership . METHODS Surgeons were queried for their choice of bowel preparation , factors influencing their practice , and their impression of the strength and relevance of the adult literature to pediatric practice . RESULTS Surgeons who used MBP alone ( 31 % ) cited a reduction in stool burden and infectious complications as important factors , whereas surgeons choosing not to use OA ( 70 % ) reported a lack of benefit in reducing infectious complications as the primary reason . Although 53 % of surgeons reported that evidence from adult literature was the most important influence , 73 % of surgeons reported there was poor evidence supporting the use of OA ( ±MBP ) , and only 25 % used a preparation supported by adult r and omized data . CONCLUSIONS Wide variation exists among pediatric surgeons in the perceived utility of MBP and OA . Although the majority of pediatric surgeons cited the adult literature as the strongest influence on their practice , this is not consistent with stated perceptions or practice
Patients given oral beta-lactams and macrolides warrant close monitoring due to unpredictable absorption post-bariatric surgery , whereas oral fluoroquinolones and linezolid may not be affected .
Several studies also showed decreased absorption following RYGB , as well as lower serum exposure in patients with obesity compared to non-obese controls .
The purpose of this study was to conduct a systematic review of the existing literature to determine the effect of bariatric surgery on various pharmacokinetic parameters of oral antibiotic absorption as well as overall patient outcomes .