Evaluating quality of life tools in North American patients with erythropoietic protoporphyria and X-linked protoporphyria.

BackgroundErythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare photodermatoses presenting with severe phototoxicity. Although anecdotally, providers who treat EPP patients acknowledge their life-altering effects, tools that fully capture their impact on quality of life (QoL) are lacking.MethodsAdult patients with EPP/XLP were given four validated QoL tools: the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), the Hospital Anxiety and Depression Scale (HADS), the Illness Perception Questionnaire Revised (IPQR), and an EPP-Specific tool. All patients received the PROMIS-57 while the HADS, IPQR, and EPP-Specific tools were introduced at a later date. Associations between responses and clinical phenotypes were explored.ResultsTwo hundred and two patients were included; 193 completed PROMIS-57, 104 completed IPQR, 103 completed HADS, and 107 completed the EPP-Specific tool. The IPQR showed that patients strongly believed EPP/XLP had a negative impact on their lives. Mean scores in anxiety and depression domains of both HADS and PROMIS-57 were normal; however, anxiety scores from HADS were borderline/abnormal in 20% of patients. The EPP-Specific tool revealed a decreased QoL in most patients. The PROMIS-57 showed that 21.8% of patients have clinically significant pain interference. Several tool domains correlated with measures of disease severity, most being from the PROMIS-57.ConclusionsImpaired QoL is an important consequence of EPP/XLP. PROMIS-57 was most sensitive in evaluating impaired QoL in EPP/XLP. Further research is needed to compare the effectiveness of it for assessing response to treatment

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial

Background The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. Methods Adult patients (\u3e= 18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1: 1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. Findings Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4.10, exceeding the prespecified stopping boundary value of 2.87). At this point, outcome data were available for 223 patients (mean follow-up 33.3 months [SD 19.7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10.1%) patients in the medical management group compared with 35 (30.7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0.27, 95% CI 0.14-0.54). No harms were identified, other than a higher number of strokes (45 vs 12,

Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as the kidney are largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) and morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using samples and datasets available from 11 spaceflight-exposed mouse and 5 human, 1 simulated microgravity rat and 4 simulated GCR-exposed mouse missions. We found that spaceflight induces: 1) renal transporter dephosphorylation which may indicate astronauts' increased risk of nephrolithiasis is in part a primary renal phenomenon rather than solely a secondary consequence of bone loss; 2) remodelling of the nephron that results in expansion of distal convoluted tubule size but loss of overall tubule density; 3) renal damage and dysfunction when exposed to a Mars roundtrip dose-equivalent of simulated GCR

Residual gas analysis in ISX-A

A computer-controlled mass analyzer was utilized to observe the residual gases in the ISX-A tokamak. This residual gas analysis (RGA) system enabled time resolved measurements of preselected m/e peak heights to be made during and after tokamak discharges. Routine mass scans were also made and displayed in the form of semilogarithmic plots of partial pressure (torr) versus m/e. Wall conditioning of the stainless steel torus consisted of hydrogen discharge cleaning and titanium gettering, which ultimately produced gage pressures on the order of 10/sup -8/ and 10/sup -9/ torr, respectively. The dominant plasma impurities, carbon and oxygen, were observed by the RGA as light hydrocarbons and water vapor. Entrapment of deuterium by the walls was investigated by monitoring the residual D/sub 2/ content after the working gas was changed to H/sub 2/. The effective nuclear charge (Z/sub eff/) was found to be proportional to the residual contaminants measured by the RGA immediately following a discharge

Recovery Efficiency Test Project: Phase 1, Activity report. Volume 1: Site selection, drill plan preparation, drilling, logging, and coring operations

The recovery Efficiency Test well project addressed a number of technical issues. The primary objective was to determine the increased efficiency gas recovery of a long horizontal wellbore over that of a vertical wellbore and, more specifically, what improvements can be expected from inducing multiple hydraulic fractures from such a wellbore. BDM corporation located, planned, and drilled a long radius turn horizontal well in the Devonian shale Lower Huron section in Wayne County, West Virginia, demonstrating that state-of-the-art technology is capable of drilling such wells. BDM successfully tested drilling, coring, and logging in a horizontal well using air as the circulating medium; conducted reservoir modeling studies to protect flow rates and reserves in advance of drilling operations; observed two phase flow conditions in the wellbore not observed previously; cored a fracture zone which produced gas; observed that fractures in the core and the wellbore were not systematically spaced (varied from 5 to 68 feet in different parts of the wellbore); observed that highest gas show rates reported by the mud logger corresponded to zone with lowest fracture spacing (five feet) or high fracture frequency. Four and one-half inch casting was successfully installed in the borehole and was equipped to isolate the horizontal section into eight (8) zones for future testing and stimulation operations. 6 refs., 48 figs., 10 tabs

Erythropoietic protoporphyria: time to prodrome, the warning signal to exit sun exposure without pain—a patient-reported outcome efficacy measure

Purpose: Patients with erythropoietic protoporphyria (EPP), a severe painful photodermatosis, experience prodromal sensations when exposed to sunlight, which are the “warning signals” to exit the sun, as prolonged exposure causes an excruciatingly painful phototoxic attack. The unique prodromal cutaneous sensations are reversible and differ from the severe burning pain attack lasting 2–7 days. Previously, afamelanotide treatment was studied using time to pain or time outside as primary outcome measures. Since patients have an ingrained fear of sunlight, these measures did not capture the full treatment effect. We retrospectively characterized and evaluated time to prodrome (TTP) as a safer, patient-reported outcome (PRO) measure in afamelanotide-treated patients. Methods: Structured interviews recorded TTP before and during afamelanotide treatment in retrospective US and Dutch cohort studies. Results: Thirty-one US and 58 Dutch EPP patients participated. Before afamelanotide treatment, 54.8% US and 39.7% Dutch patients reported TTP onset <10 minutes in direct sunlight. In both studies, patients’ TTP’s were significantly longer during afamelanotide treatment (p < 0.0001). All US patients’ TTP increased; no TTP was <10 minutes. Among Dutch patients 81% improved; only 10.3% reported TTPs < 10 minutes. Conclusion: EPP patients reported substantial improvements in TTP during afamelanotide treatment. TTP could provide a safer, PRO-based efficacy endpoint for assessing future EPP treatments