Perioperative risk predictors for gender affirming surgery in the NSQIP database.

INTRODUCTION: Gender affirming surgeries (GAS), such as phalloplasty (PLPs) and vaginoplasty (VGPs), are important aspects of medical care for transgender patients. Here, we aim to better characterize patient demographics and surgical outcomes for PLPs and VGPs using the National Surgical Quality Improvement Program (NSQIP). We hypothesized that frailty indices would be predictive of perioperative PLP and VGP risk and outcomes for PLPs and VGPs. MATERIALS AND METHODS: Primary GAS, specifically PLPs and VGPs performed from 2006-2020 were identified in NSQIP. Baseline frailty was based on NSQIP's modified frailty index (mFI) and preoperative morbidity probability (morbprob) variable. RESULTS: Fifty-eight PLPs and 468 VGPs were identified. The overall 30-day complication rate for PLP was 26%, with 17% of total patients experiencing minor complications and 16% experiencing major complications. The overall, minor, and major complication rates for VGP were 14%, 7%, and 9% respectively. Readmissions and reoperations occurred in 7% PLP and 5% VGP patients. No deaths occurred in either group within 30 days. The mFI scores were not predictive of 30-day complications or LOS. NSQIP morbprob was predictive of 30-day complications for both PLP (OR 4.0, 95% CI 1.08-19.59, p = 0.038) and VGP (OR 2.39, 95% CI 1.46-3.97, p = 0.0005). NSQIP's morbprob was also predictive of extended LOS for PLP patients (6.3 ± 1.3 days, p = 0.03). CONCLUSIONS: This study describes patient characteristics and complication rates of PLPs and VGPs. The NSQIP preoperative morbprob is an effective predictor of surgical complications and is better than the mFI.

Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis.

Various sensors that detect double-stranded RNA, presumably of viral origin, exist in eukaryotic cells and induce IFN-responses. Ongoing IFN-responses have also been documented in a variety of human autoimmune diseases including relapsing-remitting multiple sclerosis (RRMS) but their origins remain obscure. We find increased IFN-responses in leukocytes in relapsing-remitting multiple sclerosis at distinct stages of disease. Moreover, endogenous RNAs isolated from blood cells of these same patients recapitulate this IFN-response if transfected into naïve cells. These endogenous RNAs are double-stranded RNAs, contain Alu and Line elements and are transcribed from leukocyte transcriptional enhancers. Thus, transcribed endogenous retrotransposon elements can co-opt pattern recognition sensors to induce IFN-responses in RRMS.

Assessing the impact of health-care access on the severity of low back pain by country: a case study within the GBD framework.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time. METHODS: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios. FINDINGS: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable. INTERPRETATION: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions. FUNDING: Bill and Melinda Gates Foundation and Queensland Health.

Grading disorder severity and averted burden by access to treatment within the GBD framework: a case study with anxiety disorders.

BACKGROUND: The Global Burden of Disease Study (GBD) estimates burden by cause with major relevance for resource allocators globally. Non-fatal burden estimates are influenced by disorder severity. However, for many disorders, global severity is sourced from a single high-income country survey. We aimed to estimate severity distributions that vary by Healthcare Access Quality Index (HAQI) using anxiety disorders as a case study and present the usefulness of this method in simulating averted and avoidable burden globally. METHODS: In this case study, we estimated treatment use among respondents with anxiety disorder in the 1997 Australian National Survey of Mental Health and Wellbeing (NSMHWB), the source used to estimate severity of anxiety disorders in GBD. Treatment effects were sourced from the Cochrane Database of Systematic Reviews and pooled via network meta-analysis. Severity distribution was established via a meta-regression of their disability weights, derived from 12-item short form survey scores. We simulated the shift in severity across scenarios without access to treatment and with full access to optimal treatment (cognitive behavioural therapy and antidepressants). We interpolated this shift linearly along the HAQI, extrapolated country-specific severity from HAQI scores, and calculated averted and avoidable burden. FINDINGS: The database review sourced 56 reviews, of which eight were eligible for inclusion. These eight reviews reported on 156 randomised controlled trials, with 194 treatment effects. Respondents to the 1997 NSMHWB consisted of 5936 women (55·8%) and 4705 (44·2%) men aged 18 years or older (mean age and ethnicity data not available). The survey-weighted treatment effect size was -0·28 (95% uncertainty interval -0·45 to -0·12). The pooled treatment effect for full coverage optimal treatment was -1·07 (-1·47 to -0·64). The sequela-weighted disability weight among people with anxiety disorder in the NSMHWB was 0·141 (0·042 to 0·275). The estimated disability weight was 0·188 (0·070 to 0·341) after removing the benefits of treatment and 0·056 (0·013 to 0·140) after providing all people with anxiety disorder access to optimal treatment. Globally, 12·5% (4·6 to 21·5) of anxiety disorder burden was averted because of available treatment. However, 71·1% (46·2 to 87·6) of global anxiety disorder burden could be averted if all people with anxiety disorders had access to optimal treatment. INTERPRETATION: Because it is based on guidance from a single survey done in one high-income country, the burden of anxiety disorders in low-income and middle-income countries is probably underestimated by GBD. Despite the availability of effective treatments, low use of these treatments means that most burden is still avoidable. Most of the burden could be averted if all people with anxiety disorders had access to optimal treatment, highlighting the importance of public promotion and referral pathways of treatment for anxiety disorders. Location-specific severity distributions in GBD would greatly increase precision in burden estimates and highlight avertable burden to clinicians, public health practitioners, and policy makers. FUNDING: Queensland Health and Bill & Melinda Gates Foundation.