[IMPACT OF CLINICAL PHARMACIST CONSULTATIONS ON RATE OF COMPLICATIONS, RE-HOSPITALIZATIONS AND MORTALITY IN PATIENTS UNDERGOING BARIATRIC SURGERY].

BACKGROUND: Patients undergoing bariatric surgery are prone to changes in absorption, improvement in their chronic diseases and other pharmacokinetic/pharmacodynamic alteration which can affect continuation and the required doses of their chronic medications. OBJECTIVES: To examine the effect of a clinical pharmacist's consultation on the rate of complications, re-hospitalizations and mortality among patients who underwent bariatric surgery. METHODS: In this retrospective cohort study, results of bariatric patients who were consulted by a clinical pharmacist between the years 2013-2019 were compared with the results of a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years. The intervention cohort included bariatric patients members of Clalit Health Services, who were treated at the Herzliya Medical Center and who were identified by the treating staff as complex cases requiring drug counseling. The primary outcomes measured in the study included: rates of surgical complications, re-hospitalizations, and death up to one year after surgery. RESULTS: The intervention group included 165 patients; the 12 month rate of re-hospitalization in the intervention group was 10.9% vs. 19.5% in the comparison group (p=0.005). The rate of documented postoperative complications was 2.7% vs. 3.9% (p=0.462) and mortality was null vs. 0.16%. CONCLUSIONS: Although the intervention population was identified in advance as more complex in terms of age and background morbidity, the rate of re-hospitalization and mortality was significantly lower in the intervention group than in the general bariatric surgery population in Israel. These results demonstrate the importance of referring to a specialized clinical pharmacist around bariatric surgery for improving patient safety, especially in complex patients.

Case Report of Increased Exposure to Antiretrovirals following Sleeve Gastrectomy.

Bariatric surgery is increasingly performed in morbidly obese HIV patients. Limited data exist regarding antiretroviral drug exposure after bariatric surgery. We report a case of a morbidly obese HIV patient who underwent sleeve gastrectomy. Abacavir, lamivudine, and dolutegravir therapeutic drug monitoring was performed at several time points pre- and postsurgery. Significantly increased levels were measured, particularly for abacavir, whose levels increased ∼12-fold. Several mechanistic explanations for these findings are discussed.

Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP.

BACKGROUND: Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery. METHODS: A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards. RESULTS: Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure. CONCLUSION: This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions.

[DIAGNOSIS, TREATMENT AND PREVENTION OF GASTROINTESTINAL DISEASES PRE AND POST BARIATRIC SURGERY PROCEDURES].

INTRODUCTION: In the last decade, the number of bariatric surgery procedures increased dramatically in Israel similar to what has occurred worldwide. Bariatric surgery procedures have a proven efficacy in the treatment of morbid obesity. However, post-operative complications that involve the gastrointestinal tract may occur. Beyond the importance of early diagnosis and treatment, it is crucial to understand that we may decrease and prevent some of the complications by selecting the bariatric procedure according to the patient's medical background. This review addresses diagnosis, treatment and prevention of gastrointestinal diseases pre- and post-bariatric surgery procedures. Recommended pre-operative diagnostic procedures are listed including the eradication of helicobacter pylori and the protective effect of proton pump inhibitors. We reviewed the effect of specific bariatric procedures on gastroesophageal reflux disease and on intestinal motility. Prevention and treatment of nutritional deficits and metabolic complications are also discussed. Finally, this document was written by a panel of experts representing the attitudes of the Israeli Societies for Metabolic and Bariatric Surgery (ISMBS), Pharmaceutical (PSI), Study of Obesity and the Israeli Gastroenterology and Liver Diseases Association, all endorsed by the Institute for Quality in Medicine of the Israeli Medical Association (IMA).

Bariatric surgery in solid organ transplant patients: Long-term follow-up results of outcome, safety, and effect on immunosuppression.

The surgical risk of transplanted patients is high, and the modified gastrointestinal anatomy after bariatric surgery (BS) may lead to pharmacokinetic alterations in the absorption of immunosuppressive drugs. Data on outcomes of BS and the safety and feasibility of maintaining immunosuppression and graft safety among solid organ transplanted patients are scarce. In the current study, weight loss, improvement in comorbidities, and changes in dosage and trough levels of immunosuppression drugs before and after BS were analyzed for all transplanted patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in our institution between November 2011 and January 2017. Thirty-four patients (13 females, 21 males, average age 53 years) were included in the study. A successful weight loss (>50% excess weight loss in 28 of them [82%]) was recorded at the last follow-up. Comorbidities improved significantly. Immunosuppressive stability increased from 39% to 47% among all patients. The tacrolimus blood trough levels declined slightly, but remained within therapeutic range. These data suggest that LSG and LRYGB ensure good immunosuppressive maintenance together with significant weight loss and improvement in comorbidities without serious graft rejection or dysfunction. The surgical risk is higher than in the regular BS population.

[DRUG THERAPY FOLLOWING BARIATRIC SURGERY: EXAMINATION OF POTENTIAL IMPACT AND CLINICAL RECOMMENDATIONS].

INTRODUCTION: Bariatric surgery is the most effective solution for morbid obesity, and the number of patients undergoing bariatric surgery is rapidly and constantly growing. The modified gastrointestinal (GI) anatomy of the patient may lead to significant pharmacokinetic alterations in the oral absorption of drugs after surgery. However, due to insufficient available literature and inadequate awareness of the medical team, bariatric surgery patients may be discharged from the hospital with insufficient instructions regarding their medication therapy. In this article, we aim to present the various mechanisms by which bariatric surgery may influence oral drug absorption, to provide an overview of the currently available literature on the subject, and to present guidelines on instruction recommendations that bariatric surgery patients should receive before leaving the hospital. To date, and until more robust data is published, it is essential to follow and monitor patients closely to enhance the safety and efficacy of their medication therapies, both in the immediate and long term periods post-surgery.

Reducing Cost and Intravenous Duration of Nicardipine in Intracerebral Hemorrhage Patients via an Interdisciplinary Approach.

BACKGROUND: The mainstay of acute management of intracerebral hemorrhage (ICH) is blood pressure reduction. Intravenous (IV) nicardipine is an effective but costly intervention for blood pressure reduction in the intensive care unit (ICU). Earlier transition to oral (PO) antihypertensive agents may reduce ICU length of stay (LOS) and associated costs. We sought to study the effectiveness of an interdisciplinary intervention to start earlier transition to PO antihypertensives. METHODS: From July 2011 to July 2012, patients with ICH who received IV nicardipine were reviewed and screened for eligibility by an interdisciplinary team including physicians and pharmacists. These patients were compared to a control group 1 year prior to this intervention. The duration of nicardipine treatment (median hours), estimated costs, and ICU LOS were measured. RESULTS: A total of 35 patients and 44 controls were studied. The median hours of IV nicardipine use were significantly decreased from a baseline mean of 118 to 30 hours (P < .001); total cost savings per year was $433,566 ($18,475 per patient). The average LOS remained similar (8.4 versus 8.9 days, P < .990). In a follow-up study 1 year later, after the intervention was no longer used, a sample of 21 consecutive patients was reviewed and the duration of IV nicardipine treatment had increased to a mean of 96 hours. CONCLUSION: A physician and pharmacist-led project to initiate oral antihyperintensive medications earlier was successful in reducing the duration of IV nicardipine treatment in patients with ICH while leading to substantial cost savings.

Time from onset of SIRS to antibiotic administration and outcomes after subarachnoid hemorrhage.

INTRODUCTION: The interval from presentation with systemic inflammatory response syndrome (SIRS) to the start of antibiotic administration affects mortality in patients with sepsis. However, patients with subarachnoid hemorrhage (SAH) often develop SIRS directly from their brain injury, making it a less useful indicator of infection. We therefore hypothesized that SIRS would not be a suitable trigger for antibiotics in this population. METHODS: We examined the time from the development of SIRS until antibiotic initiation and its relationship to long-term neurological outcomes in patients with nontraumatic SAH. Patients' baseline characteristics, time of antibiotic administration, and hospital course were collected from retrospective chart review. The primary outcome, 6-month functional status, was prospectively determined using blinded, structured interviews incorporating the modified Rankin Scale (mRS). RESULTS: Sixty-six of 70 patients with SAH during the study period had 6-month follow-up and were included in this analysis. SIRS developed in 57 patients (86%, 95% CI 78-95%). In ordinal logistic regression models controlling for age and illness severity, the time from SIRS onset until antibiotic initiation was not associated with 6-month mRS scores (OR per hour, 0.994; 95% CI 0.987-1.001). CONCLUSIONS: In this cohort of patients with SAH, time from SIRS onset until antibiotic administration was not related to functional outcomes. Our results indicate that SIRS is nonspecific in patients with SAH, and support the safety of withholding antibiotics in those who lack additional evidence of infection or hemodynamic deterioration.

Can Consultation by a Clinical Pharmacist Prevent Morbidity and Mortality in Patients Undergoing Bariatric Surgery?

The purpose of this work was to investigate the effect of clinical pharmacist consultation on the long-term morbidity and mortality outcomes among patients undergoing bariatric surgery. In this retrospective cohort study, 165 bariatric patients at Herzliya Medical Center who were identified as complex cases and were consulted by a clinical pharmacist (2013-2019) were compared with a wider group of bariatric patients with chronic diseases who were recorded in the Israeli General Bariatric Registry during the same years. The primary outcomes were rates of surgical complications, re-hospitalizations, and death up to one year after surgery. The secondary outcome was the rate of re-hospitalizations in different time periods. The twelve (12)-month rate of re-hospitalization in the intervention group was 10.9% vs. 19.5% in the comparison group (p = 0.005); the rate of documented postoperative complications was 2.7% vs. 3.9% (p = 0.462), and mortality was null vs. 0.16%, respectively. As for the secondary outcomes, the rates of re-hospitalizations in the periods of 0-30, 31-90, 91-180, and 181-365 days after surgery were 1.8% vs. 5.3% (p = 0.046), 2.4% vs. 4.1% (p = 0.278), 3.6% vs. 4.8% (p = 0.476), and 7.3% vs. 9.9% (p = 0.256) in the intervention vs. comparison cohorts, respectively. In conclusion, this study demonstrates the importance and benefit of referring to a specialized clinical pharmacist around bariatric surgery for improving patient safety, especially in complex patients. This is the first study to look at the long-term effects of clinical pharmacist consultation on re-hospitalization and mortality among bariatric patients, and our encouraging outcomes should hopefully stimulate more studies to show the invaluable role of specialized clinical pharmacists.

Publicly Funded Cancer Care: Are Adjuvant Therapies Prioritized Over Treatment of Metastatic Cancer? The Israeli Experience.

PURPOSE: In Israel, a public committee advises which new medications should be reimbursed subject to an annual budget allocation. The committee considers clinical trial outcomes, professional societies' preferences, projected budget impacts, and other social and ethical aspects. The Israeli oncologists' society places a strong emphasis on prioritizing adjuvant therapies because of their potential to advance cure. In 2023, several novel adjuvant therapies were suggested for national funding. Our objective was to ascertain whether Israeli decision makers have embraced the practice of prioritizing budgets for therapies with curative intent over late-disease therapy. METHODS: We collected data on all proposed cancer therapies for the 2023 update: indications, treatment settings, European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) score, and whether accepted for reimbursement. The rates of acceptance were compared between drugs in curative and noncurative settings. Data were extracted from the official Israeli Ministry of Health publications and ESMO-MCBS website. RESULTS: Seven of the eight proposed therapies with curative intent received reimbursement approval (88%), in contrast to 11 of the 55 therapies for advanced/metastatic stages (20%). Among all advanced disease therapies with a high ESMO-MCBS score of 4, only four of 16 (25%) secured reimbursement approval. CONCLUSION: Our analysis revealed that during the 2023 reimbursement deliberations, Israeli policymakers embraced the prioritization of potentially curative therapies over treatments for incurable cancers, including several interventions that have demonstrated significant improvements in overall survival and/or quality of life. Introducing objective cost-effectiveness measures as a guiding framework for comparing competing medications may offer some resolution to this complex challenge.

Lamotrigine therapy in patients after bariatric surgery: Potentially hampered solubility and dissolution.

Bariatric surgery is an effective treatment of obesity and related comorbidities. With surgery, the stomach undergoes major anatomical/physiological changes that may affect the oral exposure of drugs, especially marginally soluble weak bases, such as lamotrigine. The aim of this work was to study the solubility/dissolution of lamotrigine in conditions simulating the stomach before vs. after bariatric surgery. Lamotrigine solubility was studied in-vitro, as well as ex-vivo in gastric content aspirated from patients before vs. after bariatric surgery. We then compared the dissolution kinetics of various marketed lamotrigine products in pre- vs. post-operative stomach conditions, different in volume, pH, agitation strength and speed. Decreased lamotrigine solubility with increasing pH (from 1.37 ± 0.09 (pH = 1) to 0.22 ± 0.03 mg/mL (pH = 7)) was obtained. Twelve-fold higher lamotrigine solubility was revealed in gastric content aspirated before vs. after surgery (8.5 ± 0.7 and 0.7 ± 0.01 mg/mL, respectively). Dissolution studies showed that only the lowest dose (25 mg) fully dissolved in the post-surgery stomach conditions, while at higher doses, lamotrigine tablet dissolution was impaired. Neither fast-dissolving tablet, nor tablet crushing, helped resolving this problem. Based on these results, and given that dissolution of the drug dose governs the subsequent absorption, close monitoring of this essential drug is advised after bariatric surgery.

Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery.

Bariatric surgery may alter the absorption and overall bioavailability of oral drugs. Lamotrigine is a major antiepileptic and mood stabilizer, that its use after bariatric surgery has not yet been studied. In this article, we provide a thorough mechanistic analysis of the effects of bariatric surgery on multiple mechanisms important for the absorption, bioavailability and overall pharmacokinetics of lamotrigine. Attributable to its pharmacokinetic properties and drug characteristics, the use of lamotrigine after bariatric surgery may be challenging. The complex situation in which some mechanisms may lead to increased drug exposure (e.g., decreased metabolism, weight loss) while others to its decrease (e.g., hampered dissolution/solubility, decreased gastric volume), may result in lowered, unchanged, or enhanced lamotrigine plasma levels after the surgery. We conclude with a set of clinical recommendations for lamotrigine treatment after bariatric surgery, aiming to allow better patient care, and emphasizing the extra caution that needs to be taken with these patients.

Seven key parameters that facilitate clinical pharmacy practice: a comparison between Israel and the United States.

Clinical pharmacists have advanced training that enables them to manage medication therapy, including prescribing, titrating, and discontinuing medications, in order to achieve therapeutic goals. In some countries, such as the United States, advances in training, responsibility, legal frameworks, and public acceptance of new roles have proceeded in parallel to expand the scope and contribution of clinical pharmacists over several decades. In this manuscript, we detail seven discrete key parameters of professional advancement for clinical pharmacists, corresponding to the seven areas in which they must advance in order to contribute fully to delivering high-quality medical care. For each key parameter, we briefly summarize the progress made in the United States to date, as well as goals for future progress. We then compare this to the development of the analogous key parameter in Israel. We found that on some key parameters, the development of clinical pharmacy in Israel lags behind the United States. This manuscript can provide a roadmap for the future advancement of clinical pharmacy in Israel, toward its full realization as a profession that can contribute to delivering high-quality medical care.

Sleeve Gastrectomy Failure-Revision to Laparoscopic One-Anastomosis Gastric Bypass or Roux-n-Y Gastric Bypass: a Multicenter Study.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is the most popular bariatric procedure performed worldwide. However, many patients undergo secondary surgery due to either weight-related and complication-related reasons or both. Conversional options vary with one-anastomosis gastric bypass (OAGB) and Roux-n-Y gastric bypass (RYGB) being the most common. The aim of the study was to assess the safety and efficacy of converting failed LSG to either OAGB or RYGB, and compare weight-related results and post-conversion complications. METHODS: Retrospective review of hospital records of patients who underwent conversion from LSG to either RYGB or OAGB due to insufficient weight loss or weight regain in 7 bariatric centers between 2013 and 2019. Data retrieved included demographics, anthropometrics, comorbidities, indication for conversion, conversion type, complications, and weight loss. RESULTS: During the study period, 396 patients were included in the study. Eighty-four (21%) patients were lost to follow-up. RYGB and OAGB were performed in 119 and 144 patients, respectively. Mean age and body mass index (BMI) at revision were 44.2 years (range 19-72) and 40.6 ± 5.9 kg/m2 (range 35-71), respectively. Of these, 191 (73%) were female. Percent total body weight loss (%TWL) was 16% ± 1% for the RYGB group vs. 23% ± 12% for the OAGB group (p = 0.0007) at a median follow-up of 29 months (range 7-78 months) following conversion. Gastroesophageal reflux disease (GERD) was significantly higher 1 year following conversion to OAGB vs. RYGB occurring in 25 (17.4%) and 9 (7.6%) patients, respectively (p = 0.018). CONCLUSIONS: Conversion of LSG to OAGB, compared to RYGB, results in increased weight loss but a higher rate of GERD and potential nutritional deficiencies.

Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review, meta-analysis, network meta-analysis, and meta-regression.

BACKGROUND: Many health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function. OBJECTIVE: We aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism. SETTING: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to December 2020 for relevant clinical studies. Random-effects model was used to pool results. Network meta-analysis was performed, incorporating direct and indirect comparisons among different types of bariatric surgery. Meta-regression analysis was performed to evaluate the impact of moderator variables on TSH levels and required levothyroxine dose after surgery. We followed the PRISMA guidelines for data selection and extraction. PROSPERO registry number: CRD42018105739. RESULTS: A total of 28 studies involving 1284 patients were included. There was a statistically significant decrease in TSH levels after bariatric surgery (mean difference = -1.66 mU/L, 95%CI [-2.29, -1.03], P < .0001). In meta-regression analysis, we found that the following moderator variables: length of follow-up, mean age, baseline TSH, and preoperative thyroid function, could explain 1%, 43%, 68%, and 88% of the between-study variance, respectively. Furthermore, subclinical hypothyroidism was completely resolved in 87% of patients following bariatric surgery. In addition, there was a statistically significant decrease of levothyroxine dose in frank hypothyroid patients following bariatric surgery (mean difference = -13.20 mcg/d, 95%CI [-19.69, -6.71]). In network meta-analysis, we found that discontinuing or decreasing levothyroxine dose was significant following Roux-en-Y gastric bypass, 1 anastomosis gastric bypass, and sleeve gastrectomy, (OR = 31.02, 95%CI [10.34, 93.08]), (OR = 41.73, 95%CI [2.04, 854.69]), (OR = 104.03, 95%CI [35.79, 302.38]), respectively. CONCLUSIONS: Based on our meta-analysis, bariatric surgery is associated with the resolution of subclinical hypothyroidism, a decrease in TSH levels, and a decrease in levothyroxine dose.

Treatment of COVID-19 Patients Post-Bariatric Surgery: Issues for Consideration.

As COVID-19 has been expanding rapidly around the world, the types of patients and their backgrounds vary. The substantially altered GI anatomy/physiology after bariatric surgery presents new challenges to the field of oral drug therapy. In this report we highlight issues for consideration when treating COVID-19 patients who previously underwent bariatric surgery and provide practical tools to allow optimal care of these patients. Post-bariatric absorption/pharmacokinetic changes may warrant dose adjustment, as well as the use of liquid oral dosage forms or parenteral routes of administration, if available. Realizing the potentially altered pharmacokinetics of various drugs after bariatric surgery is essential for providing optimal pharmacological therapy and overall patient care.

Vitamin K-what is known regarding bariatric surgery patients: a systematic review.

Vitamin K, a fat-soluble vitamin, is involved in blood coagulation, bone mineralization, inhibition of vascular calcification, and regulation of numerous enzyme systems. Patients who undergo bariatric surgery (BS), especially procedures that involve a malabsorptive component, are prone to develop vitamin K deficiency (VKD). The causes of VKD include decreased absorptive surface areas, steatorrhea, bacterial overgrowth, marked reduction of carriers of vitamin K, decrease in vitamin K intake, and modifications of gut microbiota. Data on vitamin K status among BS patients are scarce and the strength of evidence supporting vitamin K supplementation is weak. Thus, this systematic review summarized the scientific literature on vitamin K and examined the status among patients before and after BS, as well as among pregnant women with a history of BS. A MEDLINE/Pubmed and Embase electronic search was performed. After a thorough screening of 204 titles, 19 articles were selected by 2 independent reviewers. Five studies on BS candidates (n = 750), 12 studies after BS (n = 1442), and 4 studies on pregnant woman after BS (n = 83, of them n = 7 from case reports) were included. Results of the current review suggest that patients who undergo major malabsorptive surgeries are at a higher risk of developing VKD and should be better monitored. At this point, it is still unclear whether supplementation of vitamin K is required, and what oral dose or vitamer type should be used to normalize serum levels after different types of bariatric procedures. It should be noted that the current protocols for VKD treatment are still experiential in these patients. It is also unknown at what intervals screening tests for vitamin K should be performed and what assay is most appropriate for screening purposes. Future studies are needed to answer these unresolved issues.

Lithium Toxicity with Severe Bradycardia Post Sleeve Gastrectomy: a Case Report and Review of the Literature.

Lithium is one of the major treatment options in bipolar disorder. Bariatric surgery can significantly modify the oral bioavailability of drugs, and lithium is no exception; although in most cases drug absorption seems to decrease, in the case of lithium, toxicity is the risk. In this article, we describe a 61-year-old male patient presented with lithium toxicity, including newly diagnosed severe bradycardia requiring a permanent pacemaker, after undergoing sleeve gastrectomy. We discuss the mechanisms behind this case, provide potential solutions for clinicians treating bariatric patients with lithium, and review previous reports of lithium toxicity post bariatric surgery. Awareness of changes in drug absorption, particularly lithium, following bariatric surgery, is prudent and essential for optimal patient care. Close clinical and drug levels monitoring is strongly advised.

Oral levothyroxine therapy postbariatric surgery: Biopharmaceutical aspects and clinical effects.

BACKGROUND: Bariatric surgery can lead to changes in the oral absorption of many drugs. Levothyroxine is a narrow therapeutic drug for hypothyroidism, a common condition among patients with obesity. OBJECTIVE: The purpose of this work was to provide a mechanistic overview of levothyroxine absorption, and to thoroughly analyze the expected effects of bariatric surgery on oral levothyroxine therapy. METHODS: We performed a systematic review of the relevant literature reporting the effects of bariatric surgery on oral levothyroxine absorption and postoperative thyroid function. A PubMed search for relevant keywords resulted in a total of 14 articles reporting levothyroxine status before versus after bariatric surgery. RESULTS: Different mechanisms may support opposing trends as to levothyroxine dose adjustment postsurgery. On the one hand, based on impaired drug solubility/dissolution attributable to higher gastric pH as well as reduced gastric volume, compromised levothyroxine absorption is expected. On the other hand, the great weight loss, and altered set-point of thyroid hormone homeostasis with decreased thyroid-stimulating hormone after the surgery, may result in a decreased dose requirement. CONCLUSIONS: For patients after bariatric surgery, close monitoring of both the clinical presentation and plasma thyroid-stimulating hormone and T4 levels is strongly advised. Better understanding and awareness of the science presented in this article may help to avoid preventable complications and provide optimal patient care.

Increased Paracetamol Bioavailability after Sleeve Gastrectomy: A Crossover Pre- vs. Post-Operative Clinical Trial.

Oral drug bioavailability may be significantly altered after laparoscopic sleeve gastrectomy (LSG), the most popular bariatric procedure worldwide. Paracetamol (acetaminophen) is the post-bariatric analgesic/antipyretic drug of choice. In this work we studied and analyzed the LSG effects on systemic bioavailability and pharmacokinetics of paracetamol after oral administration of solid vs. liquid dosage form. A 4-armed, pharmacokinetic, crossover trial was performed in patients enrolled for LSG. Single paracetamol dose (500 mg), as caplet (n = 7) or syrup (n = 5), was administered before vs. 4-6 months post-LSG. Bioavailability was enhanced after LSG; in the caplet groups, average AUC0-t increased from 9.1 to 18.6 µg·h/mL with AUC0-t difference of 9.5 µg·h/mL (95% CI 4.6-14.5, p = 0.003). Cmax increased from 1.8 (95% CI 1.2-2.5) to 4.2 µg/mL (3.6-4.8) after LSG (p = 0.032). In the syrup groups, AUC0-t increased from 13.4 to 25.6 µg·h/mL, with AUC0-t difference of 12.2 µg·h/mL (95% CI 0.9-23.5, p = 0.049). Cmax changed from 5.4 (95% CI 2.5-8.4) to 7.8 µg/mL (6.1-9.6), and systemic bioavailability was complete (102%) after the surgery. Overall, decreased paracetamol exposure in obesity, with recovery to normal drug levels (caplet) or even higher (syrup) post-LSG, was revealed. In conclusion, attention to paracetamol effectiveness/safety in obesity, and after bariatric surgery, is prudent.