Pelvic pain and early IUD discontinuation: a prospective cohort study

Background: The aim of the study is to assess if pelvic pain is a risk factor for intrauterine device (IUD) discontinuation within one year of placement.Methods: This is a prospective cohort study of women who had IUDs inserted at a family planning office for the primary intent of contraception. Baseline pelvic pain characteristics were assessed using a validated pelvic pain questionnaire.  Women were contacted at 1 year to assess IUD continuation.Results: From February 1, 2014 to August 11, 2015 authors enrolled a sample of 179 women.  Of the 179 enrolled,163 participants completed the questionnaire, 98 reported a history of baseline pelvic pain and 65 reported no history of baseline pelvic pain. 20 participants were lost to follow-up. 86 women in the pelvic pain and 57 in the no pelvic pain group were included in the final analysis. Discontinuation rates at one year follow up were 25.6% (22) and 35.1% (20) respectively. There was no significant difference in those with and without pelvic pain discontinuing IUDs at one year (p = 0.22).Conclusions: Baseline generalized pelvic pain may not be a risk factor for IUD discontinuation within one year of placement

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

Statistical Issues in Platform Trials with a Shared Control Group

Platform trials evaluating multiple treatment arms against a shared control are an efficient alternative to multiple two-arm trials. Motivated by a randomized clinical trial of the effectiveness of two neuroprotection devices during aortic valve surgery against a control, this dissertation addresses two open questions in the optimal design of these trials. First, to explore whether multiplicity adjustments are necessary in a platform design, simulation studies evaluating the operating characteristics of platform designs relative to independent two-arm trials were conducted. Under the global null hypothesis, relative to a set of two-arm trials, we found that platform trials have slightly lower familywise error; however, conditional error rates for an experimental treatment being declared effective given another was declared effective are above the nominal alpha-level. Adjusting for multiplicity reduces familywise error, but has little impact on conditional error. These studies show that multiplicity adjustments are unnecessary in platform trials of unrelated treatments. Second, to determine the optimal approach for comparing delayed entry arms to the shared control, five methods for incorporating historical controls into two-arm trials were applied to the analyses of simulated open platform trials and compared to pooling all controls. We found that when response rates are constant, pooling yields the lowest error and most precise, unbiased estimates. However, if drift occurs, pooling results in type I error inflation or deflation depending on the direction of drift, as well as biased estimates. Although superior to naive pooling, none of the alternatives explored guarantee error control or unbiased estimates in the presence of drift. Thus, only concurrent controls should be used as comparators in the primary analysis of confirmatory studies. Finally, these findings were applied to assess the design and analysis of the neuroprotection trial

Hysterectomy at the time of risk-reducing surgery in BRCA carriers

In this study, women at risk for BRCA were surveyed to understand their choice of prophylactic surgery and associated risk of uterine cancers. The study was conducted as an anonymous online web-based survey that assessed personal and family histories and choice of prophylactic surgery. Respondents were targeted through social media groups that bring awareness to hereditary breast and ovarian cancer.The study cohort included an international group of 601 respondents. The majority were female (99.3%), in their 40s (34.2%), and had completed college or graduate school (68.8%). 87% of respondents carry BRCA gene mutation. Of 339 respondents who underwent risk-reducing salpingo-oophorectomy (RRSO), 55.8% had a hysterectomy at time of RRSO. Most common reasons for hysterectomy at time of RRSO included: 39% provider recommendation, 27.6% personal desire, 9.7% benign indications, 1.6% cancer in uterus, 1.1% precancerous uterine lesion, and 21.1% other (N = 185). In this cohort, nine were diagnosed with uterine cancer. Three were diagnosed after risk-reducing surgery. Both patients with uterine serous carcinoma were BRCA1 carriers.Two thirds of BRCA carriers surveyed had undergone RRSO. Of these, more than half had hysterectomy at time of RRSO. One third chose to have hysterectomy based on surgeon recommendation. <1% (2 out of 258) of BRCA1 gene mutation carriers reported being diagnosed with uterine serous carcinomas. While this incidence is low, it may be an underestimate based on the limitations of this study. Additional studies are needed to select which patients will benefit from concurrent hysterectomy and RRSO

A pilot study of oral iron therapy in erythropoietic protoporphyria and X-linked protoporphyria

The use of iron supplementation for anemia in erythropoietic protoporphyria (EPP) is controversial with both benefit and deterioration reported in single case reports. There is no systematic study to evaluate the benefits or risks of iron supplementation in these patients. We assessed the potential efficacy of oral iron therapy in decreasing erythrocyte protoporphyrin (ePPIX) levels in patients with EPP or X-linked protoporphyria (XLP) and low ferritin in an open-label, single-arm, interventional study. Sixteen patients (≥18&nbsp;years) with EPP or XLP confirmed by biochemical and/or genetic testing, and serum ferritin ≤30&nbsp;ng/mL were enrolled. Baseline testing included iron studies, normal hepatic function, and elevated plasma porphyrins and ePPIX levels. Oral ferrous sulfate 325&nbsp;mg twice daily was administered for 12&nbsp;months. The primary efficacy outcome was the relative difference in total ePPIX level between baseline and 12&nbsp;months after starting treatment with iron. Secondary measures included improvement in serum ferritin, plasma porphyrins, and clinical symptoms. Thirteen patients had EPP (8 females, 5 males) and 3 had XLP (all females) and the mean age of participants was 38.8&nbsp;years (SD 14.5). Ten patients completed all study visits limiting interpretation of results. In EPP patients, a transient increase in ePPIX levels was observed at 3&nbsp;months in 9 of 12 (75%) patients. Iron was discontinued in 2 of these patients after meeting the protocol stopping rule of a 35% increase in ePPIX. Seven patients withdrew before study end. Ferritin levels increased on iron replacement indicating an improvement in iron status. A decrease in ePPIX was seen in both XLP patients who completed the study (relative difference of 0.67 and 0.5 respectively). No substantial changes in ePPIX were seen in EPP patients at the end of the study (n&nbsp;=&nbsp;8; median relative difference: -0.21 (IQR: -0.44, 0.05). The most common side effects of iron treatment were gastrointestinal symptoms. Hepatic function remained normal throughout the study. Our study showed that oral iron therapy repletes iron stores and transiently increases ePPIX in some EPP patients, perhaps due to a transient increase in erythropoiesis, and may decrease ePPIX in XLP patients. Further studies are needed to better define the role of iron repletion in EPP. Trial registration: NCT02979249