SummaryBackgroundHyperbaric oxygen has been used as a therapy for patients experiencing chronic intestinal syndromes after pelvic radiotherapy for decades, yet the evidence to support the use of this therapy is based almost exclusively on non-randomised studies. We aimed to provide conclusive results for the clinical benefits of hyperbaric oxygen in patients with chronic bowel dysfunction after radiotherapy for pelvic malignancies.MethodsHOT2 was a double-blind, sham-controlled, phase 3 randomised study of patients (≥18 years) with chronic gastrointestinal symptoms for 12 months or more after radiotherapy and which persisted despite at least 3 months of optimal medical therapy and no evidence of cancer recurrence. Participants were stratified by participating hyperbaric centre and randomly assigned (2:1) by a computer-generated list (block size nine or 12) to receive treatment with hyperbaric oxygen therapy or sham. Participants in the active treatment group breathed 100% oxygen at 2·4 atmospheres of absolute pressure (ATA) and the control group breathed 21% oxygen at 1·3 ATA; both treatment groups received 90-min air pressure exposures once daily for 5 days per week for a total of 8 weeks (total of 40 exposures). Staff at the participating hyperbaric medicine facilities knew the allocated treatment, but patients, clinicians, nurse practitioners, and other health-care professionals associated with patients' care were masked to treatment allocation. Primary endpoints were changes in the bowel component of the modified Inflammatory Bowel Disease Questionnaire (IBDQ) score and the IBDQ rectal bleeding score 12 months after start of treatment relative to baseline. The primary outcome was analysed in a modified intention-to-treat population, excluding patients who did not provide IBDQ scores within a predetermined time-frame. All patients have completed 12 months of follow-up and the final analysis is complete. The trial is registered with the ISRCTN registry, number ISRCTN86894066.FindingsBetween Aug 14, 2009, and Oct 23, 2012, 84 participants were randomly assigned: 55 to hyperbaric oxygen and 29 to sham control. 75 (89%) participants received 40 pressure exposures, all participants returned the IBDQ at baseline, 75 (89%) participants returned the IBDQ at 2 weeks post-treatment, and 79 (94%) participants returned the IBDQ at 12 months post-start of treatment. Patients were excluded from analyses of co-primary endpoints if they had missing IBDQ scores for intestinal function or rectal bleeding at baseline or at 12 months. In an analysis of 46 participants in the active treatment group and 23 participants in the control group, we found no significant differences in the change of IBDQ bowel component score (median change from baseline to 12 months of 4 (IQR −3 to 11) in the treatment group vs 4 (−6 to 9) in the sham group; Mann-Whitney U score 0·67, p=0·50). In an analysis of 29 participants in the active treatment group and 11 participants in the sham group with rectal bleeding at baseline, we also found no significan...

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Information on the economic benefits of natural resource improvement is an important, yet often overlooked, consideration in environmental decision-making. In 2010, the Environmental Protection Agency established the Chesapeake Bay Total Maximum Daily Load (TMDL) that set regulatory limits for nitrogen, phosphorus, and sediment needed to restore the Chesapeake Bay. Meanwhile, the Bay jurisdictions developed implementation plans to achieve these limits. Environmental benefits of achieving the TMDL would accrue due to on-the-ground changes in land use and land management that improve the health, and therefore productivity, of land and water in the watershed. These changes occur both due to the outcomes of achieving the TMDL (i.e., cleaner water) and as a result of the measures taken to achieve those outcomes. This study quantified these changes, then translated them into dollar values for various ecosystem services, including water supply, food production, recreation, and aesthetics. We estimate the total economic benefit of implementing the TMDL at $22.5 billion per year (in 2013 dollars), as measured as the improvement over current conditions, or at $28.2 billion per year (in 2013 dollars), as measured as the difference between the TMDL and a business-as-usual scenario. These considerable benefits should be considered alongside the costs of restoring the Chesapeake Bay.

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