The effect of non-steroidal anti-inflammatory drugs on severity of acute pancreatitis and pancreatic necrosis.

Introduction Acute pancreatitis (AP) is a common emergency presentation and can be disabling. There is significant morbidity and mortality associated with AP, and it places a considerable burden on the healthcare system. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have a protective effect in some elective contexts. This retrospective study aimed to evaluate the effect of NSAIDs on the course of AP and the severity of the disease. Methods A retrospective analysis was carried out of 324 patients admitted as an emergency with a diagnosis of AP to two UK hospitals. Patients were divided into two groups: those already taking NSAIDs for other co-morbidities and those not taking NSAIDs. Variables compared included: admission to a high dependency or intensive care unit; pancreatic necrosis; pseudocyst development; need for surgery; serum inflammatory markers; modified early warning scores on days 1, 3 and 5; length of stay; and mortality. Results Patients not taking NSAIDs were more likely to have a C-reactive protein level of ≥150mg/l (p=0.007). Patients in the NSAID group experienced less pancreatic necrosis (p=0.019) and lower rates of pseudocyst formation (p=0.010). Other variables showed no difference between the two groups, specifically length of stay and mortality. Conclusions Routine NSAID use may exert a protective effect on the development of AP, its severity, and complications. Therapeutic use of NSAIDs in acute presentations with pancreatitis should be further evaluated.

Fasting gut hormone levels change with modest weight loss in obese adolescents.

BACKGROUND: Gut hormones change with weight loss in adults but are not well studied in obese youth. OBJECTIVE: The primary aim was to evaluate how gut hormones and subjective appetite measure change with dietary weight loss in obese adolescents. METHODS: Participants were a subset of those taking part in the 'Eat Smart Study'. They were aged 10-17 years with body mass index (BMI) > 90th centile and were randomized to one of three groups: wait-listed control, structured reduced carbohydrate or structured low-fat dietary intervention for 12 weeks. Outcomes were fasting glucose, insulin, leptin, adiponectin, total amylin, acylated ghrelin, active glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide (GIP), pancreatic polypeptide (PP) and total peptide tyrosine-tyrosine. Pre- and postprandial subjective sensations of appetite were assessed using visual analogue scales. RESULTS: Of 87 'Eat Smart' participants, 74 participated in this sub-study. The mean (standard deviation) BMI z-score was 2.1 (0.4) in the intervention groups at week 12 compared with 2.2 (0.4) in the control group. Fasting insulin (P = 0.05) and leptin (P = 0.03) levels decreased, while adiponectin levels increased (P = 0.05) in the intervention groups compared with control. The intervention groups were not significantly different from each other. A decrease in BMI z-score at week 12 was associated with decreased fasting insulin (P < 0.001), homeostatic model of assessment-insulin resistance (P < 0.001), leptin (P < 0.001), total amylin (P = 0.03), GIP (P = 0.01), PP (P = 0.02) and increased adiponectin (P < 0.001). There was no significant difference in appetite sensations. CONCLUSIONS: Modest weight loss in obese adolescents leads to changes in some adipokines and gut hormones that may favour weight regain.

Impact of an integrated model of care on potentially preventable hospitalizations for people with Type 2 diabetes mellitus.

AIMS: To evaluate the impact of an integrated model of care for patients with complex Type 2 diabetes mellitus on potentially preventable hospitalizations. METHODS: A prospective controlled trial was conducted comparing a multidisciplinary, community-based, integrated primary-secondary care diabetes service with usual care at a hospital diabetes outpatient clinic. Study and hospital admissions data were linked for the period from 12 months before to 24 months after commencement of the trial. The primary outcome was the number of potentially preventable hospitalizations with diabetes-related principal diagnoses. Length of stay once hospitalized was also reported. RESULTS: Of 327 adult participants, 206 were hospitalized and accounted for 667 admissions during the study period. Compared with the usual care group, patients in the integrated model of care group were nearly half as likely to be hospitalized for a potentially preventable diabetes-related principal diagnosis in the 24 months after study commencement (incidence rate ratio 0.53, 95% CI 0.29, 0.96; P = 0.04). The magnitude of the result remained similar after adjusting for age, sex, education and baseline HbA1c concentration (incidence rate ratio 0.54, 95% CI 0.29, 1.01; P = 0.05).When hospitalized, patients in the integrated care group had a similar length of stay compared with those in the usual care group (median difference -2 days, 95% CI -6.5, 2.3; P = 0.33). CONCLUSIONS: Patients receiving the integrated model of care had a reduction in the number of hospitalizations when the principal diagnosis for admission was a diabetes-related complication. Integrated models of care for people with complex diabetes can reduce hospitalizations and help attempts to curtail increasing demand on finite health services.

Model of care for the management of complex Type 2 diabetes managed in the community by primary care physicians with specialist support: an open controlled trial.

AIMS: To evaluate patient outcomes for a novel integrated primary/specialist model of community care for complex Type 2 diabetes mellitus management compared with outcomes for usual care at a tertiary hospital for diabetes outpatients. METHODS: This was a prospective open controlled trial performed in a primary and tertiary care setting in Australia. A total of 330 patients with Type 2 diabetes aged >18 years were allocated to an intervention (n=185) or usual care group (n=145). The intervention arm was a community-based model of care led by a general practitioner with advanced skills and an endocrinologist partnership. Usual care was provided via the hospital diabetes outpatient department. The primary end point was HbA(1c) concentration at 12 months. Secondary end points included serum lipids and blood pressure. RESULTS: The mean change in HbA1c concentration in the intervention group was -9 mmol/mol (-0.8%) at 12 months and in the usual care group it was -2 mmol/mol (-0.2%) (95% CI -5,1). The percentage of patients in the intervention group achieving the HbA(1c) target of ≤53 mmol/mol (7%) increased from 21 to 42% (P<0.001); for the usual care group there was a 1% increase to 39% of patients attaining this target (P=0.99). Patients in the intervention group experienced significant improvements in blood pressure and total cholesterol compared with those in the usual care group. The percentage of patients achieving clinical targets was greater in the intervention group for the combined target of HbA(1c) concentration, blood pressure and LDL cholesterol. CONCLUSIONS: A community-based, integrated model of complex diabetes care, delivered by general practitioners with advanced skills, produced clinical and process benefits compared with a tertiary diabetes outpatient clinic.

Germicidal activity of antimicrobials and VIOlight Personal Travel Toothbrush sanitizer: an in vitro study.

OBJECTIVES: The study evaluated the antibacterial effect of VIOlight (VL) Personal Travel Toothbrush Sanitizer on biofilms after toothbrush exposure to human saliva compared to Listerine Antiseptic (LA), 3% hydrogen peroxide (3%HP) and water. METHODS: Twenty toothbrush heads (n=5/Gp) were immersed in saliva and to allow for bacterial growth and biofilm formation for 24h. VL sanitizer and antiseptic(s) were used for 7 min; after treatment, brush heads were rinsed and placed into 10 mL of 2x AOAC Letheen Broth, sonicated and vortexed for 10s. Tenfold serial dilutions were prepared and plated and incubated aerobically and anaerobically. Log(10)CFU/mL data were compared utilizing ANOVA (p<0.05). RESULTS: Results showed 3%HP with significantly lower counts than LA, VL and control for aerobic and anaerobic bacteria. LA had significantly lower counts than VL and control for both types of bacteria and VIOlight had significantly lower counts than the control for aerobic bacteria. 3%HP and LA were most effective in rapidly killing bacteria when compared to VIOlight. CONCLUSIONS: Results showed that 3% hydrogen peroxide was most effective in reducing the numbers of both aerobic and anaerobic bacteria present on the toothbrush heads. Under the same test conditions, Listerine Antiseptic was shown to be secondarily effective for the same bacteria while the VIOlight unit was the least effective when compared to the other treatment groups.

Partnership for rehabilitation: looking beyond impairments.

Rehabilitation of leprosy-affected persons extends beyond the physical domain of prevention and treatment of impairments. A holistic rehabilitative approach should include addressing those problems that people may have in activities and difficulties that may prevent people from fully participating in social functions, i.e. being fully accepted as integrated members of the societies and communities to which they belong. This article highlights the activities of the Partnership for the Rehabilitation Program (PFR) of the International Nepal Fellowship (INF), Pokhara, Nepal. These activities aim to prevent, reduce or alleviate problems and difficulties that leprosy-affected persons may face in being respected and being contributing members of the communities of which they are a part.

pH modulation of Ca2+ responses and a Ca2+-dependent K+ channel in cultured rat hippocampal neurones.

1. The effects of changes in extra- and intracellular pH (pHo and pHi, respectively) on depolarization-evoked rises in intracellular free Ca2+ concentration ([Ca2+]i) and the activity of a Ca2+-dependent K+ channel were investigated in cultured fetal rat hippocampal neurones. 2. In neurones loaded with 2', 7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (BCECF), changes in pHo evoked changes in pHi. At room temperature, the ratio DeltapHi : DeltapHo (the slope of the regression line relating pHi to pHo) was 0.37 under HCO3-/CO2-buffered conditions and 0.45 under Hepes-buffered conditions; corresponding values at 37 C were 0.71 and 0.79, respectively. The measurements of changes in pHi evoked by changes in pHo were employed in subsequent experiments to correct for the effects of changes in pHi on the Kd of fura-2 for Ca2+. 3. In fura-2-loaded neurones, rises in [Ca2+]i evoked by transient exposure to 50 mM K+ were reduced and enhanced during perfusion with acidic and alkaline media, respectively, compared with control responses at pHo 7.3. Fifty percent inhibition of high-[K+]o-evoked rises in [Ca2+]i corresponded to pHo 7.23. In the presence of 10 microM nifedipine, 50 % inhibition of high-[K+]o-evoked responses corresponded to pHo 7.20, compared with a pHo of 7.31 for 50% inhibition of [Ca2+]i transients evoked by N-methyl-D-aspartate. 4. Changes in pHi at a constant pHo were evoked by exposing neurones to weak acids or bases and quantified in BCECF-loaded cells. Following pH-dependent corrections for the Kd of fura-2 for Ca2+, rises in [Ca2+]i evoked by high-[K+]o in fura-2-loaded cells were found to be affected only marginally by changes in pHi. When changes in pHi similar to those observed during the application of weak acids or bases were elicited by changing pHo, reductions in pH inhibited rises in [Ca2+]i evoked by 50 mM K+ whereas increases in pH enhanced them. 5. The effects of changes in pH on the kinetic properties of a BK-type Ca2+-dependent K+ channel were investigated. In inside-out patches excised from neurones in sister cultures to those used in the microspectrofluorimetric studies, with internal [Ca2+] at 20 microM, channel openings at an internal pH of 6.7 were generally absent whereas at pH 7.3 (or 7.8) the open probability was high. In contrast, channel activity in outside-out patches was not affected by reducing the pH of the bath (external) solution from 7.3 to 6.7. In inside-out patches with internal [Ca2+] at 0.7 microM, a separate protocol was applied to generate transient activation of the channel at a potential of 0 mV following a step from a holding level of -80 mV. In this case open probabilities were 0.81 (at pH 7.8), 0.57 (pH 7.3), 0.19 (pH 7.0) and 0.04 (pH 6.7). Channel conductance was not affected by changes in internal pH. 6. The results indicate that, in fetal rat hippocampal neurones, depolarization-evoked rises in [Ca2+]i mediated by the influx of Ca2+ ions through dihydropyridine-sensitive and -resistant voltage-activated Ca2+ channels are modulated by changes in pHo. The effects of pHo cannot be accounted for by changes in pHi consequent upon changes in pHo. However, changes in pHi affect the unitary properties of a Ca2+-dependent K+ channel. The results support the notion that pHo and/or pHi transients may serve a modulatory role in neuronal function.

Characterization of acid extrusion mechanisms in cultured fetal rat hippocampal neurones.

1. We investigated the mechanisms regulating acid extrusion in cultured fetal rat hippocampal neurones loaded with 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. 2. In the absence of HCO3-, removal of external Na+ by substitution with N-methyl-D-glucamine caused a sustained intracellular acidification that was not observed when Na+ was replaced by Li+, but neither steady-state intracellular pH (pHi) nor the rate of pHi recovery from an imposed acid load were influenced by amiloride analogues or HOE 694, inhibitors of Na(+)-H+ exchange in other cell types. In the presence of HCO3-, removal of external Na+ or Cl- evoked an intracellular acidification and a 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid-sensitive (DIDS-sensitive) intracellular alkalinization, respectively. Applied alone, however, DIDS elicited a fall in steady-state pHi at room temperature but not at 37 degrees C. The DIDS-evoked fall in steady-state pHi and the 0 Cl(-)-evoked intracellular alkalinization observed in the presence of HCO3- at room temperature were dependent on external Na+. 3. At room temperature (18-22 degrees C), but not at 37 degrees C, the transition from HCO3(-)-free to HCO3(-)-containing medium at a constant pHo produced a net alkalinization that was dependent on external Na+ and was inhibited by DIDS or the depletion of internal Cl-. 4. Recovery of pHi from an acid load imposed in the absence of HCO3- was dependent on external Na+. Addition of HCO3- to the perfusion medium increased the rate of pHi recovery from an acid load at room temperature but not at 37 degrees C. In the presence of HCO3-, DIDS slowed the rate of recovery of pHi from an acid load at both room temperature and at 37 degrees C. 5. Recovery of pHi following an imposed intracellular acidification to pH < 6.5 could occur in the absence of external Na+, providing that HCO3- was present in the perfusate. This slow, Na(+)-independent recovery of pHi from very low levels of intracellular pH was sensitive to DIDS. 6. The results indicate that acid extrusion in cultured fetal rat hippocampal neurones involves primarily two Na(+)-dependent mechanisms, one HCO3- dependent (a HCO3(-)-Cl- exchanger) and the other HCO3- independent (possibly a Na(+)-H+ exchanger). Although both mechanisms participate in the maintenance of steady-state pHi at room temperature, only the HCO3(-)-independent mechanism does so at 37 degrees C.