Citation Classics and Trends in the Field of Opioids: A Bibliometric Analysis.

Introduction Bibliometric analysis is one of the emerging and latest statistical study type used to examine and keep a systemic record of the research done on a particular topic of a certain field. A number of such bibliometric studies are conducted on various topics of the medical science but none existed on the vast topic of pharmacology - opioids. Hence, we present a bibliometric analysis of the 'Citation Classics' of opioids. Method The primary database chosen to extract the citation classics of opioids was Scopus. Top 100 citation classics were arranged according to the citation count and then analyzed. Results The top 100 citation classics were published between 1957 and 2013, among which seventy-two were published from 1977 to 1997. Among all nineteen countries that contributed to these citation classics, United States of America alone produced sixty-three classics. The top three journals of the list were multidisciplinary and contained 36 citation classics. Endogenous opioids were the most studied (n=35) class of opioids among the citation classes and the most studied subject was of the neurosciences. Conclusion The subject areas of neurology and analgesic aspects of opioids are well established and endogenous and synthetic opioids were the most studied classes of opioids. However, the egregious issues of addiction and misuse of opioids were underrepresented in the citation classics. The pulmonary and gastrointestinal aspects of opioids are also marginalized among the citation classics.

Treatment Outcomes of Hepatitis C-Infected Patients in Specialty Clinic vs. Primary Care Physician Clinic: A Comparative Analysis.

BACKGROUND: Oral direct-acting antivirals (DAAs) provide an exceptional opportunity to treat hepatitis C virus (HCV) infection. GOALS: We compared the treatment outcomes between specialty and primary care physician (PCP) clinics for patients treated with DAAs. METHODS: We performed a retrospective analysis of patients treated for HCV in our PCP clinics and specialty; liver and gastroenterology clinics and gastroenterology clinics. We used the two-sided t-test and the chi-square test to compare the means of continuous and categorical variables, respectively. RESULTS: Data from a total of 377 patients was analyzed (PCP clinic: n = 185 and specialty clinic: n = 192). There was no significant difference between age, race, and gender. Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores were comparable at baseline. Greater than 90% of the patients achieved sustained virological response (SVR) with no difference between the groups. CONCLUSIONS: Uncomplicated patients can be treated for hepatitis C by their PCPs with DAAs with similar treatment outcomes to specialty clinics. There should be explicit guidelines on patient eligibility for treatment by PCPs vs. specialists.

Lubiprostone in the treatment of chronic idiopathic constipation: an update on health-related quality of life and patient-reported outcomes.

Chronic idiopathic constipation, if inadequately treated, can be bothersome with a detrimental effect on patients' quality of life (QOL). This may also result in frequent health care visits, increasing the burden of this ailment's medical cost. Management strategies, focused on lifestyle changes, include increased exercise, a high-fiber diet, and toilet training. Pharmacologic options include fiber supplementation, laxatives, serotonergic agents, and prosecretory agents such as lubiprostone. In this review, we were able to conclude that lubiprostone, when used for chronic idiopathic constipation, has a significantly beneficial effect on both patients' symptoms and their QOL. In multiple randomized controlled trials, it has been found to have increased the number of spontaneous bowel movements at different time endpoints. Corresponding improvements were also observed for abdominal bloating, discomfort, stool frequency, and straining symptoms among patients.

Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain.

BACKGROUND: Widespread opioid use has led to increase in opioid-related adverse effects like constipation. We examined the impact of study endpoints on reported treatment benefits. METHODS: Using MEDLINE, EMBASE, and ClinicalTrials.gov, we searched for randomized control trials targeting chronic opioid-induced constipation (OIC) and subjected them to meta-analysis. Data are given with 95% confidence intervals. RESULTS: Thirty trials met our inclusion criteria. Combining all dichotomous definitions of responders, active drugs were consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01-2.63; 15 studies], independent of the underlying drug mechanism. The choice of endpoints significantly affected the therapeutic gain. When time from drug administration to defecation was used, the OR decreased from 4.74 [2.71-4.74] at 6 h or less to 2.46 [1.80-3.30] at 24 h (P < 0.05). Using other response definitions, the relative benefit over placebo was 2.10 [1.77-2.50; 12 studies] for weekly bowel frequency, 2.03 [1.39-2.95; 9 studies] for symptom scores, 2.21 [1.25-3.90; 4 studies] for global assessment scales, and 1.27 [0.79-2.03; 7 studies] for rescue laxative use. CONCLUSION: While treatment of OIC with active drugs is more effective than placebo, the relative gain depends on the choice of endpoints. The commonly used time-dependent response definition is associated with the highest response rate but is of questionable relevance in a chronic disorder. The limited data do not clearly demonstrate a unique advantage of the peripherally restricted opioid antagonists, suggesting that treatment with often cheaper agents should be optimized before shifting to these novel expensive agents.

Immunization Against Hepatitis A Virus and Hepatitis B Virus in Patients with Chronic Liver Disease: Are We Doing a Good Job?

INTRODUCTION: In the era of highly effective vaccines for Hepatitis A Virus (HAV) and Hepatitis B Virus (HBV), acute viral hepatitis in patients with a chronic liver disease remains a public health concern. Vaccination for HAV and HBV is endorsed by all liver society guidelines. The aim of our study was to determine the rates of immunization in an internal medicine resident clinic. METHODS: We identified patients with a chronic liver disease seen at the University of Oklahoma Internal Medicine resident clinic between June 2014 and May 2015. ICD-9 code 571 was used to identify patients with a chronic liver disease. Vaccination records and patient data were reviewed. RESULTS: A total of 141 patients with a chronic liver disease (mean age 54.1 years, 56% males) were identified. Almost half of the patients (47.5%) were also being seen in the gastroenterology clinic. During the internal medicine resident clinic visit, vaccination against HAV and HBV was addressed for 50% and 46% of the patients, respectively. Patients being seen by senior residents were more likely to be immunized against HAV (OR 2.7, p=0.009) and HBV (OR 2.1, p=0.03). Patients followed in the GI clinic were more likely to be immunized against HAV (OR 2.1, p= 0.02) and HBV (OR 2.0, p=0.02). The gender of the treating physician and etiology had no impact on vaccination rates. DISCUSSION: Immunization rates for HAV and HBV remain subpar despite clear guidelines for patients with a chronic liver disease. This provides an important avenue for improvement. Different strategies, including resident education, developing vaccination protocols, and referral to the gastroenterology clinic, are likely to improve vaccination status for patients with chronic liver diseases.

The 100 Most Influential Papers and Recent Trends in the Field of Gastrointestinal Stromal Tumours: A Bibliometric Analysis.

Background Bibliometric analysis is a statistical tool used to examine the exponential growth in medical research. Many analogous analyses have been conducted, but none existed for gastrointestinal stromal tumors (GISTs). Hence, we conducted a citation analysis of the hundred most cited and recently published articles on this topic. Methods Scopus was chosen as the primary database, through which the top 100 and recent publications were ranked according to the citation count and were then analysed. Results The 100 most cited articles were published between 1992 and 2013, among which the greatest number of articles were published in the years 2002 (n = 15) and 2006 (n = 11). Amidst the 24 countries from which the articles originated, the United States of America (n = 76) topped the list. The Journal of Clinical Oncology (n = 15) and the American Journal of Clinical Pathology (n = 10) contributed majority of the top articles. Harvard Medical School alone produced 44 of the top 100. Articles from 2013 to date showed the same trend as that of top 100 articles regarding origin and institutions. Conclusion Basic science and genetics of GISTs are established, and new drugs are being studied for medicinal therapy. Surgical management and diagnostics of these tumors, however, are yet to be studied as extensively.

Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized controlled trial.

BACKGROUND AND AIMS: Chronic opioid use increases tolerance to sedatives. Diphenhydramine is recommended for difficult-to-sedate patients during endoscopic procedures. We hypothesized that the addition of diphenhydramine to midazolam and fentanyl would improve objective and subjective measures of procedural sedation. METHODS: This randomized, double-blind, placebo-controlled trial included patients on chronic opioids undergoing colonoscopy. Patients were randomized to receive 50 mg of diphenhydramine intravenously (n = 61) or placebo (n = 58), in addition to fentanyl and midazolam. Baseline characteristics, amount of fentanyl and midazolam, procedure times, and adverse events were recorded. Quality of sedation was assessed by the physician and nurse. Patients rated pain and amnesia on a 10-point scale. RESULTS: There was no difference in amounts of fentanyl (125.4 ± 56.2 µg vs 126.9 ± 53.5 µg, P = .88) and midazolam (4.9 ± 2.1 mg vs 5 ± 1.9 mg, P = .79) used. The mean sedation scores from the physician (6.2 ± 1.1 vs 5.3 ± 1.2, P =.0002) and nurses (5.6 ± 1.5 vs 5.1 ± 1.4, P =.04) were statistically significant in favor of the diphenhydramine arm. Patient scores for pain (2.05 ± 2.17 vs 3.09 ± 3.95, P =.047) and amnesia (7.8 ± 3.4 vs 6.5 ± 3.8, P =.047) favored the group that received diphenhydramine. Qualitative assessment showed no significant difference between the groups. There was no difference in induction time (P = .86), procedure duration (P = .98), or recovery time (P = .16). Hypotensive episodes were more common in the placebo group (P = .027). CONCLUSIONS: In patients on chronic opioid therapy, administration of diphenhydramine does not allow for lower doses of procedural sedatives but improves quality of sedation without increasing the number of adverse events. (Clinical trial registration number: NCT T01967433.).

Impact of sustained virologic response on short-term clinical outcomes in hepatitis C-related cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) is a common cause of cirrhosis, leading to increased morbidity and mortality. Treatment of the underlying etiology has been shown to improve fibrosis and cirrhosis. AIM: We sought to evaluate the impact of a sustained virologic response on liver chemistries, model for end stage liver disease (MELD) score, Child-Pugh-Turcotte score (CPT), and fibrosis 4 score (FIB4) in patients with liver cirrhosis secondary to HCV with portal hypertension, with or without decompensation. METHODS: Patients with HCV seen in our transplant clinic between June 2013 and September 2015 were identified using ICD-9 code 573.3. Charts were reviewed retrospectively. RESULTS: We collected data from 92 patients with a mean pretreatment MELD score of 9.16±2.98. The most common genotype was Ia, n=79 (86%). The mean duration of follow-up was 7.52±2.25 months. Transaminitis improved significantly at follow-up versus pretreatment [mean aspartate transaminase from 81.2±62.9 to 32.4±12.0 (P<0.0001); alanine transaminase 74.7±77.8 to 27.7±19.4 (P<0.0001)]. Albumin, bilirubin, and α-fetoprotein improved significantly. MELD scores improved in patients with pretreatment scores greater than 10 (P<0.0003), but not in patients with pretreatment scores less than 10 (P=0.501). The CPT score decreased from 6.1±0.9 to 5.8±0.9 (P<0.0024). The FIB4 score improved significantly in patients with baseline FIB4 more than 3.24, but not with higher baseline FIB4. CONCLUSION: Use of direct antivirals in patients with decompensated cirrhosis because of HCV leads to improved MELD, FIB4, and CPT scores.

Assessment of Pharmaceutical Company and Device Manufacturer Payments to Gastroenterologists and Their Participation in Clinical Practice Guideline Panels.

Importance: Payments from pharmaceutical and device manufacturers to physicians may influence the advice physicians give patients and peers. Objectives: To investigate the nature and amounts of monetary and other benefits that gastroenterologists received and to determine the participation of those receiving benefits in the formulation of clinical practice guidelines. Design, Setting, and Participants: This cohort study analyzed information from the Centers for Medicare & Medicaid Services Open Payments database, including all reports about payments that pharmaceutical and device manufacturers gave to adult or pediatric gastroenterologists in 2016. PubMed was used to examine the professional affiliations and publication records of top payment recipients. Panelists of clinical guidelines who also received personal financial rewards listed in the Open Payments database were identified. Main Outcomes and Measures: Payments made to gastroenterologists by pharmaceutical company and device manufacturers. Results: Of 15 497 gastroenterologists, 13 467 (86.9%) received a total of 432 463 payments accounting for a total expenditure of $67 144 862. Direct financial payments for consultations, talks, or other services were made to 2055 physicians and were responsible for 4.2% of payments (18 179 of 432 463), but for 62.7% of total expenditures ($42 086 207 of $67 144 862). Although a significant number of submissions were for food and beverages, they constituted only a small amount of total expenditure. For gastroenterologists treating adult patients, 10 products were linked to 63.8% of payments (11 221 of 17 588) related to direct financial rewards and 37.1% of the total expenditures ($24 892 643 of $67 144 862). Twenty-nine of 36 clinical practice guidelines included panelists who had received honoraria or consultation fees from industry sources, with amounts exceeding $10 000 in 8 of them (22%). Conclusions and Relevance: Most gastroenterologists accept meals or gifts from industry, with 2055 of 15 497 gastroenterologists receiving direct payments and 8 of 36 clinical practice guidelines panelists having received more than $10 000. Considering the known impact of such benefits on prescribing patterns and other professional behaviors, policy makers should consider revising regulations governing interactions with industry and disclosure formats alerting others to their potential biasing impact.

Disorders of gastrointestinal hypomotility.

Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases.

Effective Constipation Treatment Changes More Than Bowel Frequency: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: The marketing of newer agents for treatment of constipation and irritable bowel syndrome with constipation (IBS-C) emphasize improvements in abdominal pain. However, it is not clear whether this observation reflects a unique visceral analgesic effect of these agents or is a general feature of effective laxation. We sought to determine the relationship between improvements in bowel frequency and decreases in abdominal pain in clinical trials of patients with constipation or IBS-C. METHODS: We searched "PubMed" and "Embase" databanks for clinical trials in patients with constipation or IBS-C, targeting publications that provided detailed data on bowel movement frequency and pain intensity before and after an intervention. We abstracted the results and performed meta-analytic and meta-regression analyses. RESULTS: Twenty-seven trials (16 constipation and 11 IBS) met entry criteria. Baseline weekly bowel movement frequency was low with 2.35 (2.07-2.64) with differences between constipation (2.00 [1.62-2.38]) and IBS-C (2.77 [2.40-3.14]; Q = 8.18; P = 0.002). Studies reported moderate pain levels (2.12 [1.81-2.42]) with comparable baseline levels in constipation (2.02 [1.63-2.42]) and IBS-C (2.35 [2.10-2.60]; Q = 1.92; P = 0.167). Treatments increased bowel frequency by 2.17 [1.88-2.47] and lowered pain ratings by 0.58 [0.49-0.68]. Meta-regression demonstrated a significant correlation between treatment-induced increases in bowel frequency and decreased pain ratings. CONCLUSIONS: Our analysis suggests that reduction of abdominal pain observed in clinical trials of constipation and IBS-C is associated with laxation, and may not require specific drug mechanisms, thus arguing against a unique advantage of newer agents over traditional laxatives in the treatment of constipation and IBS-C.

New pharmacological treatment options for irritable bowel syndrome with constipation.

INTRODUCTION: Constipation predominant irritable bowel syndrome (IBS-C) is a common disorder and accounts for a large number of ambulatory visits. Sensory abnormalities, that is, presence of abdominal pain and discomfort, distinguish IBS-C from chronic idiopathic constipation. AREA COVERED: This review focuses on the pharmacology, efficacy, safety, and future of prucalopride, YKP-10811, DSP-6952, dexloxiglumide, linaclotide, plecanatide, tenapanor, and elobixibat. EXPERT OPINION: It is now well established that treatment focusing only on bowel transit provides incomplete relief to patients with IBS-C. Improved understanding of pathophysiology of IBS-C has led to use of sensory end points like complete spontaneous bowel movements and the FDA combined end point (abdominal pain and complete spontaneous bowel movements) in clinical trials. A number of drugs are in development and provide hope for this challenging group of patients. However, because of recent failures secondary to ineffectiveness and/or adverse events, we cautiously await how clinical data play out in larger studies and in clinical practice.

The impact of chronic opioid use on colonoscopy outcomes.

BACKGROUND: Endoscopic procedures are frequently performed on patients chronically on opioids, raising concerns about the safety and efficacy of conventional sedation. AIMS: We hypothesized that chronic opioid use is associated with longer procedure times, higher dosages of sedation medications, and an increase in adverse effects. METHODS: This is a retrospective review from June 2012 to June 2013. Patients on chronic opioids (opioids use ≥ 12 weeks) were compared to randomly selected patients matched for age, race, and sex. Multivariate regression analysis was performed to identify factors that were independently predictive of longer procedure times. RESULTS: Patients on chronic opioids required higher doses of fentanyl (122.0 ± 45.3 vs. 105.8 ± 47.2 µg; P < 0.0001) and midazolam (5.3 ± 5.3 vs. 4.4 ± 2 mg; P = 0.0037) and were more likely to receive diphenhydramine (42.8 vs. 22.6 %; P < 0.001). The induction period (11.3 ± 8.8 vs. 7.5 ± 4.0 min), duration of procedure (39.1 ± 17.5 vs. 33.4 ± 14.1 min), and recovery times (38.7 ± 15.3 vs. 33.8 ± 12.1 min) were significantly longer for patients on chronic opioids. In the multivariate regression analysis, opioid use was an independent predictor of longer procedure duration (P < 0.05). Hypotensive episodes did not differ between groups (2.8 vs. 2.7 %; P = 0.8). However, patients on chronic opioids experienced more pain (13.4 vs. 5.9 %; P 0.001) and hypertensive episodes (8.1 vs. 2.8 %; P 0.002). CONCLUSION: Patients on chronic opioids represent a high-risk population with longer procedural times and more discomfort, despite higher dosages of sedative agents. Prospective studies are required to define the risks and benefits of more costly alternative sedation strategies for patients on chronic opioids.

Mystery of hepatitis e virus: recent advances in its diagnosis and management.

Mysterious aspects of the long presumed to be well-known hepatitis E virus (HEV) have recently surfaced that distinguish it from other hepatotropic viruses. It is a cause of chronic hepatitis in immunosuppressed patients. It has human to human transmission through blood and mantains high seroprevalence in blood donors. HEV has also been found to occur more frequently in the West in those without a history of travel to endemic countries. It has varied extrahepatic manifestations and has multiple non-human reservoirs including pigs and rats. Considering these recent discoveries, it appears odd that HEV is not sought more frequently when working up acute and chronic hepatitis patients. The disease is particularly severe among pregnant women and has a high attack rate in young adults. What adds to its ambiguity is the absence of a well-established diagnostic criteria for its detection and that there is no specific antiviral drug for hepatitis E, except for isolated cases where ribavirin or pegylated interferon alpha has been used with occasional success. This review paper discusses the recent advances in the knowledge of the virus itself, its epidemiology, diagnostic approach and prevention, and the treatment options available.

Low-FODMAP Diet for Irritable Bowel Syndrome: Is It Ready for Prime Time?

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disease, which adversely affects the quality of life. Its prevalence has been reported to be around 10-15 % in North America and constitutes the most common cause for gastroenterology referral. Unfortunately, the pathophysiology of IBS is not completely understood. Not surprisingly, the management strategies can leave the patients with inadequate symptom control, making IBS a debilitating gastrointestinal syndrome. Dietary interventions as a treatment strategy for IBS have been recently evaluated. One such intervention includes dietary restriction of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs). FODMAPs define a group of short-chain carbohydrates that are incompletely absorbed in small intestine and later fermented in the colon. Evidence in the form of randomized controlled trials and observational studies have evaluated the mechanism of action and efficacy of low-FODMAP diet. This dietary intervention has showed promising results in symptom reduction in IBS patients. However, latest trials have also shown that the low-FODMAP diet is associated with marked changes in gut microbiota specifically reduction in microbiota with prebiotic properties. Implications of such changes on gastrointestinal health need to be further evaluated in future trials.

Cholecystectomy for biliary dyskinesia in gastroparesis: mimic or misfortune?

OBJECTIVES: Biliary dyskinesia and gastroparesis are associated with upper abdominal discomfort and dyspeptic symptoms in the absence of structural abnormalities. We hypothesized that the similarity in symptoms would trigger testing and surgical treatment for biliary abnormalities in a significant number of patients, with refractory symptoms ultimately demonstrating impairment of gastric function. METHODS: The study was designed as a retrospective review of patients seen between April 1, 2008 and December 31, 2009. Patients were identified using diagnosis code for gastroparesis (International Classification of Diseases, Ninth Revision code 536.3). Demographic information, duration, etiology and severity of disease, coexisting psychiatric illness, pain and functional gastrointestinal disorders, medication use, and abdominal surgery with a focus on cholecystectomy were abstracted from the medical records. RESULTS: A total of 131 patients were identified. Women predominated (77.86%), and the idiopathic form of gastroparesis was the most common etiology. A total of 59 (45%) patients had undergone cholecystectomies. Although symptomatic cholelithiasis was the primary indication, more than one-third of these patients underwent surgery for biliary dyskinesia (n = 19) or chronic acalculous cholecystitis (n = 2). In this subgroup, improvement was either absent (n = 13) or transient only (n = 8), lasting for 1.0 ± 0.6 months. Patients who underwent cholecystectomy were younger compared with the rest of the group; all other variables did not show significant differences. CONCLUSIONS: Considering the overlap and correlation between gastric and gallbladder function, we should raise the threshold for biliary dyskinesia and reassess the appropriateness of surgical therapy, especially in patients with coexisting dyspeptic symptoms.