Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study

Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design: RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Results: Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5–7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion: Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required

Alluvial evidence for major climate and flow regime changes during the middle and late Quaternary in eastern central Australia

As a low-gradient arid region spanning the tropics to the temperate zone, the Lake Eyre basin has undergone gentle late Cenozoic crustal warping leading to substantial alluvial deposition, thereby forming repositories of evidence for palaeoclimatic and palaeohydrological changes from the Late Tertiary to the Holocene. Auger holes and bank exposures at 5 locations along the lower 500 km of Cooper Creek, a major contributor to Lake Eyre in the eastern part of the basin, yielded 85 luminescence dates (TL and OSL) that, combined with a further 142 luminescence dates from northeastern Australia, have established a chronology of multiple episodes of enhanced flow regime from about 750 ka to the Holocene. Mean bankfull discharges on Cooper Creek upstream of the Innamincka Dome at 250–230 ka or oxygen isotope stages (OIS) 7–6 are estimated to have been 5 to 7 times larger than those of today, however, substantially less reworking has occurred during and after OIS 5 than before. Lower Cooper Creek appears to have similarly declined. In the Tirari Desert adjacent to Lake Eyre there is evidence of widespread alluvial activity, perhaps during but certainly before the Middle Pleistocene, yet the river became laterally restricted in OIS 7 to 5. While the Quaternary has been characterised by a dramatically oscillating wet–dry climate, since oxygen isotope stage OIS 7 or 6 there has been a general decline in the magnitude of the episodes of wetness to which the eastern part of central Australia has periodically returned. During the last full glacial cycle, Cooper Creek's periods of greatest runoff and sand transport were not during the last interglacial maximum of OIS 5e (132–122 ka) but later in OIS 5 when sea levels and global temperatures were substantially below those of 5e or today. Fluvial activity returned in OIS 4 and 3, but not to the extent of mid and late OIS 5; strongly seasonal but still powerful flows transported sand and fed source-bordering dunes in OIS 5 and 3. This chronology of fluvial activity in the late Quaternary broadly coincides with that for rivers of southeastern Australia and suggests that the wet phases in eastern central Australia have not been governed as much by the northern monsoon as by conditions in the western Pacific close to the east coast both north and south. Flow confinement within the Innamincka Dome has locally amplified Cooper Creek's energy, and here evidence exists for short but high-magnitude episodes of flow during the Last Glacial Maximum and in the early to middle Holocene, conditions that were capable of forming large palaeochannels but that were not long-lived enough to rework the river's extensive floodplains elsewhere along its length