Prevalence and predictors of pain and opioid analgesic use following total pancreatectomy with islet autotransplantation for pancreatitis.

BACKGROUND & OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is employed for the management of refractory pain in chronic pancreatitis (CP) with the prospect of partial beta cell preservation. The primary aim of this study is to evaluate the prevalence and predictors of abdominal pain and opioid use following TPIAT. METHODS: A single center cohort study of all adult patients who underwent TPIAT from 2011 to 2015 for CP. Postoperative pain outcomes included: opioid use, ongoing abdominal pain and new characteristic abdominal pain. Multiple logistic regression analysis was used to evaluate known and potential predictors of postoperative pain outcomes. RESULTS: During the study period, 46 patients underwent TPIAT. Following surgery, 89% of patients had resolution of their pre-operative abdominal pain; however, 83% of patients developed a new characteristic abdominal pain. Opioid independence was achieved in 46% of patients. Acute recurrent pancreatitis (ARP) (OR: 11.66; 95%CI: 1.47-92.39; p = 0.02) but not pain duration >3 years or ≥ 5 ERCPs was independently associated with resolution of pre-operative abdominal pain on multiple logistic regression. None of these factors were associated with cessation of opioid use. CONCLUSION: While the majority of patients have resolution of their initial abdominal pain following TPIAT, many will also develop a new characteristic abdominal pain and only half of all patients achieve opioid independence. ARP is the only independent factor associated with positive postoperative pain outcomes and should be considered a standard criterion for patient selection.

Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys.

PURPOSE: Colorectal cancer (CRC) is one of the leading causes of cancer mortality worldwide. This study examined factors influencing the choice of participants between colonoscopy and fecal immunochemical test (FIT) in a screening program and the impact of an unbiased educational session on influencing this decision. METHODS: Data from 7,845 participants who underwent screening between May 2008 and April 2011 was analyzed. Binary logistic regression and multinomial regression were performed to calculate the odds of selection of colonoscopy instead of FIT and the impact of the educational session on final participant choice, respectively. RESULTS: Of the 7,845 participants, 4,796 (61 %) underwent FIT and 3,049 (39 %) underwent colonoscopy. A significant number of participants changed their initial choice after the educational session, with 27.1 % changing to FIT from colonoscopy and 8 % changing from FIT to colonoscopy. Age, educational level, occupation, income, family history of CRC, perception of risk of CRC, and perceptions regarding CRC screening were significantly different among the groups choosing FIT and colonoscopy. Family history of CRC and high self-perception of CRC risk resulted in higher odds of choosing colonoscopy, whereas older age, single marital status, and negative perception of CRC screening resulted in lower odds. Perceptions of overall health status, occupation, low income, younger age, and negative perceptions of CRC screening were associated with higher odds of change in screening choice. CONCLUSIONS: Those at higher odds of changing CRC screening options should be supported with more detailed explanations by primary care physicians to secure a more informed and considered choice.

Primaquine radical cure of Plasmodium vivax: a critical review of the literature.

BACKGROUND: Primaquine has been the only widely available hypnozoitocidal anti-malarial drug for half a century. Despite this its clinical efficacy is poorly characterized resulting in a lack of consensus over the optimal regimen for the radical cure of Plasmodium vivax. METHODS: Published studies since 1950 of the use of primaquine regimens for preventing P. vivax relapse were reviewed. Data were extracted systematically from available papers. Primaquine regimens were categorized according to the total dose administered: very low (≤2.5 mg/kg), low (>2.5 mg/kg- < 5.0 mg/kg) and high (≥ 5.0 mg/kg). The risk of recurrent infection were summarized across geographical regions and the odds ratios between treatment regimens calculated after stratifying by total treatment dose and duration of study follow up. RESULTS: Data could be retrieved from 87 clinical trials presenting data in 59,735 patients enrolled into 156 treatment arms, conducted in 20 countries. There was marked heterogeneity in study design, particularly primaquine dosing and duration of follow up. The median rate of recurrence following very low dose of primaquine (n = 44) was 25% (range 0-90%) at 4-6 months, compared to 6.7 % (range 0-59%) following low dose primaquine (n = 82). High dose primaquine regimens were assessed in 28 treatment arms, and were associated with a median recurrence rate of 0% (Range: 0-15%) at one month. In 18 studies with control arms, the effectiveness of a very low dose primaquine regimen was no different from patients who did not receive primaquine (OR = 0.60, 95%CI 0.33-1.09, p = 0.09), whereas for the low dose regimens a significant difference was reported in 50% (6/12) of studies (overall OR = 0.14, 95%CI: 0.06-0.35, p < 0.001). Two studies enrolling 171 patients demonstrated high effectiveness of high dose primaquine compared to a control arm (OR = 0.03 (95%CI: 0.01-0.13); p < 0.0001). CONCLUSIONS: Low dose regimens retain adequate efficacy in some areas, but this is not uniform. The efficacy and safety of pragmatic high dose primaquine regimens needs to be assessed in a range of endemic and geographical locations. Such studies will require a prolonged period of follow up and comparison with control arms to account for confounding factors.

Chronic Gastrointestinal Dysmotility and Pain Following Total Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis.

BACKGROUND: The prevalence and impact of chronic gastrointestinal dysmotility following total pancreactectomy with islet autotransplantation (TP-IAT) for chronic pancreatitis is not known. METHODS: A cross-sectional study of all patients who underwent TP-IAT at our institution from August 2011 to November 2015 was undertaken. The GCSI (Gastroparesis Cardinal Symptom Index), PAGI-SYM (Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index), PAC-SYM (Patient Assessment of Constipation Symptoms), Bristol stool chart, 12-item Short Form Health Survey (SF-12), and visual analog scale for pain were administered ≥4 weeks following TP-IAT. KEY RESULTS: The prevalence of any dysmotility symptoms in patients who completed the survey (33/45, 73%) post-TP-IAT was 45%. Post-TP-IAT, the mean reduction in opioid dosing was 77.6 oral morphine equivalents (OMEs) (95% CI 32.1-123.0, p = 0.002) with 42% of patients requiring no opioids. There was significant negative correlation between dysmotility scores and SF-12 physical scores (r = -0.46, p = 0.008, 95% CI -0.70 to -0.13). Self-reported abdominal pain had significant negative correlation with both physical and mental SF-12 scores (r = -0.67, p < 0.001, 95% CI -0.83 to -0.41 and r = -0.39, p = 0.03, 95% CI -0.65 to -0.04). There was no correlation between gastrointestinal dysmotility and self-reported pain. CONCLUSIONS AND INFERENCES: Symptoms of chronic gastrointestinal dysmotility and chronic abdominal pain are common post-TP-IAT and will need to be better recognized and differentiated to improve the management of these patients.

Delayed Gastric Emptying (DGE) Following Total Pancreatectomy with Islet Auto Transplantation in Patients with Chronic Pancreatitis.

BACKGROUND: The prevalence and factors associated with delayed gastric emptying (DGE) in patients undergoing total pancreatectomy with islet auto transplantation (TP-IAT) for chronic pancreatitis are unknown. METHODS: A retrospective study of all patients who underwent TP-IAT at Johns Hopkins Hospital (JHH) from August 2011 to November 2014 was performed. The International Study Group of Pancreatic Surgery (ISGPS) clinical grading of DGE was used in this study. KEY RESULTS: A total of 39 patients with chronic pancreatitis underwent TP-IAT during the study period. The prevalence of DGE following TP-IAT was 35.9%. Twenty-five patients (64.1%) had no DGE, 10 (25.6%) had grade A, 2 (5.1%) had grade B, and 2 patients (5.1%) had grade C DGE. Patients with DGE had 5.7-fold higher odds of having a hospital length of stay (LOS) greater than 14 days (OR 5.70, 95% CI 1.37-23.76, p = 0.02). Patients undergoing laparoscopic TP-IAT had significantly shorter LOS (10.5 vs. 14 days, p = 0.02) and lower need for prokinetics (0.01) during the postoperative course. CONCLUSIONS AND INFERENCES: DGE is common after TP-IAT and can prolong LOS. Laparoscopic TP-IAT lowers LOS and need for prokinetics postoperatively. Further studies are needed to determine if laparoscopic approaches will improve long-term dysmotility.

Chemotherapeutic strategies for reducing transmission of Plasmodium vivax malaria.

Effective use of anti-malarial drugs is key to reducing the transmission potential of Plasmodium vivax. In patients presenting with symptomatic disease, treatment with potent and relatively slowly eliminated blood schizontocidal regimens administered concurrently with a supervised course of 7 mg/kg primaquine over 7-14 days has potential to exert the greatest transmission-blocking benefit. Given the spread of chloroquine-resistant P. vivax strains, the artemisinin combination therapies dihydroartemisinin + piperaquine and artesunate + mefloquine are currently the most assured means of preventing P. vivax recrudescence. Preliminary evidence suggests that, like chloroquine, these combinations potentiate the hypnozoitocidal effect of primaquine, but further supportive evidence is required. In view of the high rate of P. vivax relapse following falciparum infections in co-endemic regions, there is a strong argument for broadening current radical cure policy to include the administration of hypnozoitocidal doses of primaquine to patients with Plasmodium falciparum malaria. The most important reservoir for P. vivax transmission is likely to be very low-density, asymptomatic infections, the majority of which will arise from liver-stage relapses. Therefore, judicious mass administration of hypnozoitocidal therapy will reduce transmission of P. vivax to a greater extent than strategies focused on treatment of symptomatic patients. An efficacious hypnozoitocidal agent with a short curative treatment course would be particularly useful in mass drug administration campaigns.