A common method used by memory scholars to enhance retention is to make materials more challenging to learn—a benefit termed desirable difficulties. Recently, researchers have investigated the efficacy of Sans Forgetica, a perceptually disfluent/distinctive font which may increase processing effort required at study and enhance memory as a result. We examined the effects of Sans Forgetica relative to a standard control font  on both correct memory and associative memory errors using the Deese/Roediger–McDermott (DRM) false memory paradigm, to evaluate Sans Forgetica effects on overall memory accuracy. Across four experiments, which included nearly 300 participants, Sans Forgetica was found to have no impact on correct or false memory of DRM lists relative to a standard Arial control font, regardless of whether font type was manipulated within or between subjects or whether memory was assessed via free recall or recognition testing. Our results indicate that Sans Forgetica is ineffective for improving memory accuracy even when accounting for associative memory errors. Memory researchers are highly invested in discovering techniques that can promote memory accuracy. While dozens of strategies have been identified, including those that affect processes occurring at study and test  with the goal of producing a typeface that would aid memory retention in everyday contexts. This font is characterized by an italicized, back-slanted, and fragmented style that was suggested to encourage additional processing efforts to perceive and encode  and only slightly better 1%) than the fluent font. In a second dataset collected online, the moderate disfluent font was directly compared to a standard Arial font, and a 7% memory benefit was reported  that are directly related to a non-presented critical lure . At test, participants are highly susceptible to falsely remembering the critical lure, a pattern termed the DRM illusion. False recall can eclipse 50% . We assessed the effects of experimental design given that distinctive encoding effects such as pictorial encoding have been shown to be effective at reducing the DRM illusion in between-subject but not within-subject designs, suggesting the use of a global distinctiveness heuristic  or for perfect or near-perfect recall  suggestive of cheating (n = 4). This resulted in 43 participants available for analysis in the final dataset. A sensitivity analysis using G*POWER 3  from Roediger et al.  served aCollector, an open-source program designed to proctor web-based experiments in Psychology , or perfect or near-perfect recall  suggesting cheating (n = 7). After these participants were eliminated, 44 were available in the standard-font group, and 50 in the Sans Forgetica group. A sensitivity analysis again indicated that the sample had adequate statistical power (0.80) to detect medium effect sizes of Cohen’s d = 0.52 or larger, two-tailed. All participants reported normal or corrected-to-normal vision.One-hundred-four University of Southern Mississippi undergraduates were recruited to participate in the study for partial course credit. Participants were recruited online and were randomly assigned to either the standard-font group or the Sans Forgetica font group. Data from 10 participants were eliminated for either failing to complete memory tests for all study lists , which provides an estimate of the probability that the null hypothesis is retained. The pBIC statistic does not require the specification of priors which can be used subjectively to determine the outcome of other Bayesian methods such as Bayes factors. In addition, pBIC does not rely upon cutoffs for “strength of evidence” for the null hypothesis. Moreover, pBIC is highly sensitive to the sample size, in which large samples increase the confidence in a null effect. Because Sans Forgetica font often results in null comparisons relative to a standard/fluent font, we supplement null effects with this Bayesian analysis to increase confidence in the reliability of the results.Proportions of correct recall of list items, false recall of critical lures, and mean number of extra-list intrusions recalled per list as a function of standard and Sans Forgetica fonts are reported in Table  Masson, . In thist < 1, pBIC = 0.86, and when font type was manipulated between subjects in Experiment 1B (0.59 vs. 0.56), t(42) = 1.13, SEM = 0.03, p = 0.26, pBIC = 0.83. This equivalence extended to false recall of critical lures where Arial and Sans Forgetica fonts produced equivalent rates both in Experiment 1A (0.27 vs. 0.32), t(42) = 1.13, SEM = 0.04, p = 0.26, pBIC = 0.77, and in Experiment 1B (0.27 vs. 0.31), t < 1, pBIC = 0.86. Finally, mean numbers of extra-list intrusions per list  were rare, and did not differ between Arial and Sans Forgetica fonts in either Experiment 1A (0.27 vs. 0.26), t < 1, pBIC = 0.86, or Experiment 1B (0.26 vs. 0.22), t < 1, pBIC = 0.88. Thus, Sans Forgetica font type had no effect on correct or false recall in either within- or between-subject contexts.Correct recall was found to be equivalent for lists presented in both a standard Arial font and in the Sans Forgetica font both when font type was manipulated within subjects in Experiment 1A , Experiments 1A and 1B tested the effects of Sans Forgetica font on correct and false recall using the DRM paradigm. In doing so, we tested whether the potentially distinctive nature of Sans Forgetica would (1) improve correct recall for studied items relative to Arial font and (2) would reduce the DRM illusion by lowering false recall of non-presented critical items. Consistent with our predictions, correct recall did not differ between items presented in Sans Forgetica or Arial fonts, regardless of whether font type was manipulated within or between subjects. Similarly, false recall of non-presented critical items did not differ between font types. Thus, Sans Forgetica font was ineffective at reducing the DRM illusion relative to Arial font.Our finding that correct recall did not differ as a function of font type is consistent with previous research showing no correct memory benefit of Sans Forgetica when compared to a more perceptually fluent font  which refers to the standardized mean distance between the hit rate and false alarm distributions. We interpret d′ as an index of the amount of memory information encoded for a particular item type. This parameter can also be extended to DRM critical lures in which false alarms to critical lures are treated as hits and are compared to false alarms to critical lure controls . This analysis can therefore provide an estimate of the amount of memory information encoded for studied list items and DRM critical lures. The second parameter is a bias measure termed lambda (λ), which is computed as the z-score of 1 minus the false alarm rate to control items. Higher lambda estimates suggest a more conservative response bias, which we interpret as evidence for more (vs. less) test-based monitoring. To provide a more comprehensive assessment of Sans Forgetica effects on recognition, we provide signal detection estimates to accompany standard hit and false alarm recognition analyses.Our adoption of recognition tests also allowed for the application of a signal detection analysis to provide estimates of both encoding and monitoring processes , indicating that participants were repeatedly pressing the “old” key and were not following directions. Forty-five participants were available for analysis. A sensitivity analysis again indicated that the sample had adequate statistical power (0.80) to detect small-to-medium effect sizes of Cohen’s All study materials and procedures were the same as those used in Experiment 1A with the following exceptions. First, the recall test was replaced with an 80-item old/new recognition test in which all items were presented in the standard 32-pt. Arial font. The test was composed of 30 list items  taken from presented study lists , 10 critical lures from studied lists (5 from standard and Sans Forgetica list types), 30 list item controls taken from the counterbalanced set that was not studied (from the same positions as the list items), and 10 critical lure controls taken from the non-studied set. Participants studied all 10 lists back-to-back with an instruction screen in between indicating that a new list would be presented. Participants did not complete a filler task between lists. After the final list was presented, participants were informed that they would complete an old/new recognition test in which a test item would be presented on the center of the screen and they were to use their mouse to click on the “old” button if the word was studied, and the “new” button if the word was not studied. Participants were encouraged to respond as quickly as possible but not to compromise accuracy. Following the recognition test, participants completed the same brief demographics questionnaire and debriefing as Experiment 1A.Experiment 2B tested whether Sans Forgetica font would reduce the DRM illusion for recognition testing when font-type was manipulated between subjects. Like Experiment 2A, we again expected that correct recognition of list items would not differ between items presented in Sans Forgetica and Arial fonts. Furthermore, false recognition of critical items was expected to be reduced for lists presented in Sans Forgetica font. Thus, we expected that Sans Forgetica would not be an effective means of increasing correct recognition, but would reduce DRM false recognition in both within- and between-subject contexts.n = 5), or due to excessive misses on studied list items (hit rates < 10%), the latter of which suggests that participants were repetitively pressing the “new” button. In both cases, participants likely did not follow study instructions.d = 0.46 or larger, two-tailed. Again, all participants had normal or corrected-to-normal vision.An additional 124 University of Southern Mississippi undergraduates completed the study for partial course credit. Participants were randomly assigned to either the standard-font group, or the Sans Forgetica font group. Data from 8 participants were eliminated due to either excessive false alarms to non-studied control items .p < 0.05 level of significance was adopted for all reported analyses. For the signal detection analyses, false alarm rates of 0 and hit rates of 1 were adjusted using Macmillan and Creelman’s  was computed by taking the z-score of the hit rate for studied items minus the z-score of the false alarm rate for list item controls. For false recognition, d′ was similarly computed, but false alarms to critical lures were treated as hits and false alarms to critical lure controls were subtracted. Memory monitoring was also computed (λ), which was calculated by taking the z-score of 1 minus the false alarm rate to list item controls to estimate correct recognition monitoring, and the z-score of 1 minus the false alarm rate to critical lure controls to estimate false recognition monitoring , t < 1, pBIC = 0.87. A similar pattern was found in between-subject groups in Experiment 2B where again, hit rates were equivalent between Arial and Sans Forgetica font types (0.70 vs. 0.66), t(114) = 1.28, SEM = 0.03, p = 0.20, pBIC = 0.83, and in d′ (1.57 vs. 1.42), t(114) = 1.03, SEM = 0.14, p = 0.31, pBIC = 0.86. Given the between-subject design in Experiment 2B, estimates of memory monitoring (λ) were computed for correct recognition in both font types.t < 1, pBIC = 0.91.Starting with correct recognition of studied list items in Experiment 2A (within subjects), Arial and Sans Forgetica fonts were found to be similar in both in raw hit rates (0.70 vs. 0.70), t < 1, pBIC = 0.87, and equivalent d′ rates (1.19 vs. 1.16), t < 1, pBIC = 0.86. In Experiment 2B, false recognition of critical lures was similar between Arial and Sans Forgetica fonts (0.70 vs. 0.66), t(114) = 1.09, SEM = 0.04, p = 0.28, pBIC = 0.86, as was d′ (1.27 vs. 0.99), t(114) = 1.84, SEM = 0.15, p = 0.07, pBIC = 0.66, though this latter comparison was marginally significant, the pattern is in the direction of a Sans Forgetica advantage. Finally, standard and Sans Forgetica fonts also yielded equivalent memory monitoring for critical lures (0.65 vs. 0.54), t < 1, pBIC = 0.88.Turning to false recognition of critical lures, in Experiment 2A, standard and Sans Forgetica fonts again produced equivalent false recognition (0.66 vs. 0.65), The results of Experiments 2A and 2B are quite clear. First, consistent with our findings in Experiment 1 as well as other studies showing Sans Forgetica to be ineffective at promoting correct memory  and test-based memory monitoring (λ) were similarly equivalent between the two fonts, indicating that underlying memory processes in recognition are also not sensitive to font differences. Thus, the present study replicated previous research showing no benefit of Sans Forgetica on correct memory while subsequently extending this finding to include false memories within the DRM paradigm.Overall, Sans Forgetica consistently failed to improve correct memory for studied items, as proportions of correctly remembered list items did not differ between Sans Forgetica and Arial lists, regardless of whether participants were tested via free-recall (Experiments 1A and 1B) or recognition testing (Experiments 2A and 2B). Our experiments therefore replicate previous work showing Sans Forgetica does not produce a memorial benefit compared to an Arial control font while extending these findings to include associative word lists as opposed to cue-target pairs  for material encoded using Sans Forgetica relative to standard fonts such as Arial. For example, Taylor et al.  recentlyWhile our findings are consistent with previous research showing no benefit of Sans Forgetica on retention of studied items, a novel finding from the present study is that this font is similarly ineffective at reducing false memories in the DRM paradigm. As previous research has shown that a variety of distinctive encoding measures including generation . Further, Sans Forgetica benefits might be moderated by test expectancy processes. Geller and Peterson . Perhaps if participants could adjust the font style of Sans Forgetica items to a more readable/fluent font , a memory benefit would emerge compared to items in which participants adjust from a fluent font to another fluent font. While a disfluency resolution process is merely speculative, determining why disfluency can aid memory under generation-type conditions but not when reading specific typefaces could be important for understanding fluency effects on memory.Given that Sans Forgetica font does not appear to facilitate learning broadly , an interesting question is An additional possibility, suggested by an anonymous reviewer, is that increasing the delay between study and test might increase the effort needed to encode study materials, which in turn, may increase the likelihood of producing a desirable difficulty. In the current experiments, we used a short delay of 60 s to ensure that participants were not relying upon active information in short-term memory when making their retrievals. Increasing the delay between study and test, which would make retrieval more challenging, might increase the likelihood of a Sans Forgetica benefit on memory. While we did not make use of a delay in our study, we note that under recall testing conditions, which are recollection heavy and thus objectively more challenging than recognition testing, we did not find a Sans Forgetica pattern. It is therefore possible that increasing the delay, which may make retrieval more difficult, might not be a factor of when a Sans Forgetica benefit is found. Regardless, our experiments provide a strong test of when Sans Forgetica may affect memory accuracy using different experimental designs, different test types, and correct and false memory. The consistency of our experiments largely replicates patterns found by other researchers by showing no benefits of Sans Forgetica on correct memory, and further, we show that design and test type conditions are not boundaries for when Sans Forgetica effects emerge.In sum, the present study tested the effects of Sans Forgetica on correct memory while also assessing whether this font would be used to improve memory accuracy in the DRM paradigm by reducing false recall and recognition. Across four experiments, we replicated existing research showing that Sans Forgetica produced no benefit on correct recall/recognition of list items compared to Arial font, regardless of whether font-type was manipulated between or within subjects (e.g., Geller et al.,


Suicide rates have increased among women Veterans, with increased use of firearms as the method. Addressing suicide risk in this population requires understanding the prevalence and correlates of firearm access in healthcare settings frequented by women Veterans.Characterize the prevalence and correlates of firearm ownership and storage practices among women Veterans using Department of Veterans Affairs (VA) reproductive healthcare (RHC) services.Cross-sectional national survey conducted in 2018–2019 (17.9% response rate).n=350).Post-9/11 women Veterans using RHC  of participants reported personally owning firearms, and 38.9%  reported other household members owned firearms. Among those with firearms in or around their homes, 17.8%  and 21.9%  reported all were unsafely stored . Women who experienced recent intimate partner violence were less likely to report personally owning firearms . Those who experienced military sexual harassment , were married , or lived with other adult(s)  were more likely to report having household firearms owned by someone else. Storing firearms loaded was more prevalent among women with lifetime  or past-month  suicidal ideation and less likely among those with other adult(s) in the home . Those with parenting responsibilities  were less likely to store firearms unlocked.Firearm access is prevalent among post-9/11 women Veterans using VA RHC. Interpersonal factors may be important determinants of firearm access in this population. Safe firearm storage initiatives are needed among women Veterans using RHC, particularly for those with suicidal ideation.The online version contains supplementary material available at 10.1007/s11606-022-07587-1. Thus, there is a particular need to prevent suicide among younger post-9/11 women Veterans.From 2005 to 2018, female Veterans experienced an increase in their age-adjusted suicide rate (55.6%) that exceeded that of male Veterans (43.5%) and female non-Veterans (34.5%).3 and considering that reproductive health conditions are top health concerns reported by women Veterans under age 45.4 In particular, 43% of women Veterans in VHA care have a reproductive health diagnosis.5 Moreover, reproductive health concerns are often comorbid with mental health diagnoses,5 which can exacerbate suicide risk. Finally, given the intimate nature of RHC, women often develop sustained relationships with their RHC providers built upon trust,6 which is paramount to suicide risk assessment and prevention.7One promising approach to addressing this is implementing upstream suicide prevention initiatives within settings where women Veterans frequently receive services. While such strategies are effective in reducing suicide, less is known regarding how and where to tailor these approaches. Settings providing reproductive healthcare (RHC) may be applicable given how frequently women Veterans seek RHC from the Veterans Health Administration (VHA)2 better understanding of firearm access among women Veterans using VHA RHC would ensure upstream prevention services integrated into RHC settings are tailored to the needs of women Veterans reached by such services. Addressing firearm access in RHC settings has precedence; the American College of Obstetricians and Gynecologists recommends “periodic injury prevention evaluation and counseling regarding firearms.”8 This recommendation stems from the fact that firearm access, which can occur through personal or household ownership or unsafe storage , is associated with increased risk for suicide,11 as well as numerous other exposures and negative health outcomes that can and should be addressed in RHC settings .8An essential component to beginning to integrate suicide prevention initiatives into VHA RHC settings is understanding lethal means access among women Veterans accessing VHA RHC. As firearms are the leading means of suicide among women Veterans,12 found that military sexual trauma [MST] was a prominent theme driving firearm ownership and unsafe storage among women Veterans. Sexual assault, intimate partner violence (IPV), and post-traumatic stress disorder (PTSD) were also associated with keeping a firearm or other weapon nearby to feel safe in a larger sample of active component and Reserve/National Guard women.13Interpersonal violence, which is highly prevalent among women Veterans, may influence firearm access in this population. Monteith and colleagues14 and this association is particularly strong among women.15 Women who are the primary caregivers of children have also reported being less likely to keep a weapon nearby to feel safe.13 RHC providers are well-poised to leverage the importance of safety for all family members, including children, in the home when addressing firearm safety with their patients.Interpersonal factors, such as marital status and parenting responsibilities, are relevant to the healthcare provided in RHC settings and appear salient to women Veterans’ firearm storage practices. For example, individuals with children in the home report safer storage ,n=38) reported owning firearms and 14.4% reported residing in a household with firearm(s).16 Additionally, 13.2% of women Veteran firearm owners reported storing firearms both loaded and unlocked, and 45.4% reported either storing firearms loaded and locked or unloaded and unlocked.14 In other samples that included women Veterans, rates of household firearm access ranged from 30.7 to 39.2%.17 However, to date, no studies have examined the extent to which women Veterans using RHC own and safely store firearms, which is critical to informing upstream suicide prevention for women Veterans in RHC.Nonetheless, firearm studies have generally taken a gender-neutral approach, rarely reporting on firearm access by gender or sex. Prior studies reporting on rates of firearm access among women Veterans have yielded informative findings, but have been sparse. For example, in a nationally representative study of US adults, 24.4% of women Veterans . We also aimed to identify factors associated with women Veterans’ personal and household firearm ownership and storage, examining interpersonal factors , trauma exposure and sequelae , and suicidal ideation (SI) and attempt.This analysis was part of a larger mixed-methods study aimed at understanding suicide risk and prevention in VHA RHC settings. We used data from the Department of Veterans Affairs (VA) Corporate Data Warehouse (CDW) and VA-Department of Defense (DoD) Identity Repository to construct a random sample of 2250 post-9/11 women Veterans stratified by age and region. Inclusion criteria included being of reproductive age (18–44 years) when separating from military service and using RHC that VA provided and/or paid for in the Fiscal Year 2018. All participants separated between 10/1/2009 and 9/30/2018; thus, as some women were age 44 when separating from service in 2009, the survey sample included women with ages up to 53. RHC use was defined as having documented gynecology or women’s surgeries encounters, medical encounters outside of these settings associated with ICD-10 code(s) for qualifying reproductive health conditions or procedures and/or CPT codes for common gynecological procedures, or pharmacy fills for medications indicated solely for reproductive health conditions or contraception  with missing firearm data, the final sample included 350 women Veterans.Mailings were returned undeliverable for 129 individuals (5.7%). Of 381 who initiated the survey, 10 were ineligible, 1 opted out, and 18 did not complete the survey, resulting in 352 eligible individuals who completed the survey (response rate of 17.9%).A brief overview regarding measures is included below, with more details in Supplemental Table 19 with minor wording modifications.The survey assessed current personal and household firearm ownership. Those who endorsed either were asked if firearms were stored in or around their homes. Participants who answered affirmatively were asked if firearms in or around their homes were stored loaded and locked. Response options were dichotomized to reflect having household firearms loaded  or unlocked . Items were based on questions administered previously,20 assessed the most severe MST experienced . This approach is consistent with studies finding differential health impacts based on MST severity.22The standard VA MST screen, used extensively within VA and which has demonstrated construct validity,23 score ≥6 was used to screen for lifetime and past 12-months IPV, which has demonstrated good sensitivity and specificity with women Veterans.25A Hurt/Insult/Threaten/Scream (HITS)26 was administered to determine current provisional PTSD diagnosis and has strong test-retest reliability, internal consistency, and convergent and divergent validity.27The PTSD Checklist for DSM-5 (PCL-5)28 self-report screener assessed past-month and lifetime SI and lifetime suicide attempt.The Columbia-Suicide Severity Rating Scale (C-SSRS)Additional questions assessed race, ethnicity, age, sexual orientation, branch, deployment, combat zone, pre-9/11 military service, marital status, adult household composition, and parenting responsibilities for children under age 18. Rurality was assessed based on the urban, rural, and highly rural designations attributed to the geocoded CDW address. Region was assessed based on state of mailing address.Analyses were conducted in SAS, v9.4, and R, v3.6.0. For our first aim, we computed frequencies with 95% confidence intervals (CIs) for our four outcomes of interest: personal firearm ownership; household firearm ownership; and, in the subsample with firearms stored in or around their homes, firearm(s) stored loaded or unlocked (excluding responses of “unsure”).31 the following significantly differed between groups (p<.05) and were included as covariates in adjusted models: age and rurality ; rurality and sexual orientation (household ownership); age and combat zone service (unlocked firearms). No potential covariates were significant for models examining loaded firearms.To determine covariates, chi-square or Fisher’s exact tests were used to determine if there were significant differences based on study outcomes regarding age, race, ethnicity, sexual orientation, branch, deployment, combat zone, post-Vietnam/Peacetime service, Desert Storm/Shield service, region, and rurality. Consistent with other studies on firearm access,p-values alongside effect estimates, in accordance with guidance by Perneger32 and Rothman33, to allow readers to judge clinical and statistical significance.Log-binomial models were fit to examine unadjusted and adjusted associations between correlates of interest and firearm variables. For all models, we present Sensitivity analyses were conducted in which household firearm ownership was included as an additional covariate in the model with personal firearm ownership as the outcome, and personal firearm ownership as an additional covariate in adjusted analyses when examining household firearms as the outcome. Furthermore, for firearm storage analyses, a sensitivity analysis was conducted with the subgroup reporting personal firearm ownership.n=190) of participants reported any firearm access . Specifically, 38.00%  reported personally owning firearm(s), and 38.85%  reported that someone else in their household owned firearm(s). Among those reporting firearm access, this most frequently occurred through both personal and household firearms , rather than exclusively through personal  or household  ownership.Table n=169) indicated firearms were stored in or around their homes. Of those, 17.75%  reported all firearms were stored loaded, 22.49%  reported some were stored loaded, 52.66%  reported none were stored loaded, and 7.10%  reported being unsure. Additionally, 21.89%  reported all were stored unlocked, 14.79%  reported some were stored unlocked, 59.76%  reported none were stored unlocked, and 3.55%  were unsure.Among those with firearm access, 88.95%  and rurality : those owning firearms tended to be older and live in urban settings. There were significant differences in household firearm ownership by rurality , sexual orientation , marital status , adult household composition , parenting responsibilities , and MST , with household firearm ownership more common among those who were in urban settings, heterosexual, married, had other adult(s) residing in the home, had parental responsibilities, and had experienced military sexual harassment.There were significant between-group differences in personal firearm ownership by age  lifetime SI , and past-month SI ; those living in a household with other adult(s) were less likely to store firearms loaded, whereas those experiencing SI were more likely to store firearms loaded. For storing firearms unlocked, there were significant differences in age , combat zone service , and parenting responsibilities ; those younger, without combat zone service, and without parenting responsibilities were more likely to report storing firearms unlocked.Significant between-group differences occurred in storing firearms loaded based on adult household composition =0.75 . In the sensitivity analysis adjusting for household firearms, recent IPV was no longer associated with personal ownership: APR=0.83 .In both unadjusted and adjusted analyses, being married  and having other adult(s) residing in the home  were associated with increased prevalence of another household member owning firearms. Those with parenting responsibilities were also more likely to report household firearm ownership: PR=1.46 , but this was not significant when adjusting for rurality and sexual orientation. Although military sexual harassment was not associated with household firearms in unadjusted analyses, women who experienced military sexual harassment were more likely to report having household firearms after accounting for rurality and sexual orientation: APR=1.46 . Results were similar in sensitivity analyses adjusting for personal firearm ownership.Participants with lifetime SI, PR=1.47 , or past-month SI, PR=1.69 , were more likely to report storing firearms loaded. These associations were not significant in the sensitivity analysis limited to personal firearm owners. Those with other adult(s) living in the home were less likely to store firearms loaded .Participants with parenting responsibilities were less likely to report storing firearms unlocked in unadjusted and adjusted analyses . Results were similar in the sensitivity analysis limited to those who personally owned firearms. Those with other adult(s) living in the home were less likely to report storing firearms unlocked, but only in unadjusted analyses .and other household member(s) owning firearm(s). Considering the high prevalence of personal and household firearms in our sample, relative to other samples of women Veterans,16 it is important that providers ask about access to both personal and household firearms when assessing suicide risk with women Veterans receiving RHC. Additionally, the prevalence of unsafe firearm storage in our sample underscores the need to determine optimal ways to increase safe firearm storage  among women Veterans in RHC.To our knowledge, this study is the first to examine the prevalence and correlates of firearm access among women Veterans using VHA RHC. Findings underscore the high prevalence of firearm access in this population, which most commonly entailed personally owning firearms Women Veterans who were married or residing with other adult(s) were more likely to report living in households with firearms that other household members owned. However, those with other adult(s) living in the home were less likely to report storing firearms loaded or unlocked . Thus, including other household members in lethal means safety efforts may bolster the prevention of suicide among women Veterans.14 One possible explanation is that women Veterans with parenting responsibilities lock firearms to protect their children from firearm injuries. An important point of intervention may entail discussing risks posed to self and youths of storing household firearms unsafely.35 In other studies, adults with children at home were more likely to report believing it is at least sometimes appropriate for providers to discuss firearms with their patients;36 if supported in future research with women Veterans, this would bode well for RHC providers having such conversations with women Veterans.Parenting responsibilities also related to firearm storage. Women Veterans with parenting responsibilities were less likely to report storing firearms unlocked, consistent with other research.37 However, unexpectedly, neither MST nor probable PTSD was associated with personal firearm ownership or storage. Thus, specific trauma characteristics  or sequelae 38 may be more influential.Interpersonal violence was another salient factor associated with firearm behaviors. Women Veterans who experienced military sexual harassment were more likely to report having household firearms owned by others. One potential explanation is that, for women Veterans sexually harassed during military service, firearm access through another household member increases perceived safety.lower likelihood of personal firearm ownership before adjusting for household firearms. This is counter to a prior study in which women who experienced lifetime IPV  were twice as likely to report keeping a weapon nearby to feel safe.13 One potential explanation for our finding is that women who recently experienced IPV feel unsafe owning firearms given the ongoing threat that such firearms could be used against them.39 Additional research is warranted to further elucidate the role of IPV in women Veterans’ firearm ownership.Notably, recent IPV was associated with a 40 This suggests that, despite efforts to bolster safe firearm storage among Veterans,41 enhanced initiatives are necessary within VHA RHC settings. Recent articles have noted the import of accounting for the function of firearm access during lethal means safety discussions13 and collaboratively identifying methods to enhance safety.42 Nonetheless, as the association between SI and loaded firearms was not significant in the sensitivity analysis, additional research is warranted.Women with past-month or lifetime SI were more likely to report having loaded firearms. This finding is disconcerting as both SI and unsafe storage are risk factors for suicide.18, the overall response rate was low, with low base rates for many constructs . The focus on younger women Veterans accessing VHA RHC also limits generalizability. Our analysis of IPV, probable PTSD, and MST as categorical variables precludes examining if the severity of these factors relates to firearm access. Additionally, although we presented p-values alongside effect estimates to allow readers to judge clinical and statistical significance,33 multiple comparisons can inflate Type I error. The cross-sectional design precludes drawing conclusions regarding the directionality of observed associations. Finally, the firearm items have not been psychometrically validated.Despite minimal non-response biasThis study provides knowledge regarding firearm access among women Veterans using VHA RHC. As a substantial portion of women Veterans reported personal and/or household firearms and unsafe storage, this suggests a need to assess for firearm access and storage in this population, particularly when suicide risk is elevated. Interpersonal factors , trauma , and SI appear relevant to women Veterans’ firearm access. Incorporating these findings into suicide prevention initiatives  within VHA RHC settings is essential. In doing so, suicide prevention efforts can be tailored and delivered within a healthcare setting commonly accessed by women Veterans.ESM 1(DOCX 18 kb)ESM 2(DOCX 19 kb)


Dear Editor in Chief,Methylene blue staining: A novel application to identify the damaged tissues on the surface of pressure ulcers in detail and realised that methylene blue could be used to identify dead or damaged tissue on pressure ulcers, but we also found that there were few questions to be solved.We read the article Firstly, the number of cases in this study was relatively small, which could reduce the credibility of the article. It is expected that the authors could increase the sample size in future studies.Secondly, the article introduced the application of methylene blue to the wounds of pressure ulcers, but there was no classification to explain the clinical situations in which methylene blue was applied to the wounds. For example, whether it can be applied to all wounds, especially the identification of necrotic tissue in acute wounds. If possible, the precautions given in the application of methylene blue in acute wounds will be of key help to our clinical practice.Thirdly, if we want to determine whether it is necrotic or damaged tissue, then methylene blue needs to be applied to all tissues, so it is very necessary to propose the recommended method of methylene blue in the article. In addition, we also hope to explain the commonly used methods in the recommended methods. The description should also include the concentration of methylene blue that can accurately infiltrate the tissue and the method to ensure the infiltration of methylene blue in place.The last one is follow‐up treatment, that is to say, after using methylene blue for 24 hours, we hope that the author can explain different wound closure methods applicable to the wound.If the author can answer the above questions, it will undoubtedly improve the overall quality of the article and attract more readers.


To clarify this, we used scRNA data and viral tracking methods in order to identify HPV+ and HPV- cells in the tumour tissues of patients infected with HPV. By comparing HPV+ and HPV- malignant cells, we found a higher level of tumour stemness in HPV- tumour cells. Using tumour stemness-related genes, we established a six-gene prognostic signature that was used to divide the patients into low- and high-risk groups. It was found that HPV patients who were at low-risk of contracting HNSCC had a higher number of CD8+ T-cells as well as a higher expression of immune checkpoint molecules. Correspondingly, we found that HPV+ tumour cells expressed higher levels of CCL4, and these were highly correlated with CD8+ T cells infiltration and immune checkpoint molecules. These data suggest that the stemness features of tumour cells are not only associated with the prognostic risk, but that it could also affect the immune cell interactions and associated signalling pathways.Head and neck squamous cell carcinoma (HNSCC) usually has a poor prognosis and is associated with a high mortality rate. Its etiology is mainly the result from long-term exposure to either alcohol, tobacco or human papillomavirus (HPV) infection or a combination of these insults. However, HNSCC patients with HPV have been found to show a survival advantage over those without the virus, but the mechanism that confers this advantage is unclear. Due to the large number of HPV-independent HNSCC cases, there is a possibility that the difference in prognosis between HPV-positive (HPV HNSCC arises mainly as a result of exposure to carcinogens  or through malignant transformation due to human papillomavirus (HPV) infection. As most cases are locally advanced disease, HNSCC is associated with a poor prognosis, leading to high mortality rates. However, HPV-associated HNSCC appears to exhibit several unique biologically and clinically relevant features, with the presence of HPV conferring a survival advantage compared to its absence. A specific tumour-infiltrating immune population of CD8al cells .+ patients also appear to have a higher response rate to the programmed death 1 (PD-1) receptor and PD-1 ligand (PD-L1) ratio when compared to HPV- patients  is an emerging technology that allows judgements to be made about individual cells and facilitates the study of highly heterogeneous cell populations . In viro+ HNSCC patients and their scRNA-seq profiles. This allowed the comparison of HPV+ tumour cells with bystander tumour cells in order to investigate the relationships of HPV and the progression of HNSCC. We found that HPV- tumour cells had a higher level of tumour stemness, which was closely associated with the poor prognosis of patients with HPV- HNSCC. More importantly, we found that the enhanced tumour stemness scoring was correlated with a reduced number of infiltrated CD8 T cells in these HPV- HNSCC patients. Our data also showed a significantly decreased CCL4 directed interaction of the immune cells in HPV– HNSCC patients compared to those who were HPV+. This might account for the degree of immune infiltration of cells and the efficiency of checkpoint therapy in HPV+ HNSCC patients.In this study, we analysed the clinical data of HPV+  and HPV- HNSCC  cell lines were purchased from Sigma. UPCI : SCC090 were from ATCC. Cells were incubated in DMEM medium supplemented with 1% L−glutamine, 10% FBS and 100 U/mL penicillin/streptomycin for 24h in an atmosphere of 5% CO2:95% air. The glioma cells in the co-culture system were collected and RNA was extracted by using Trizol. Transcriptome sequencing was performed by Novogene and differential gene expression analyses were performed by using the R software package, DESeq2, according to the manufacturer’s instructions.HPVhttps://portal.gdc.carcinoma.gov/). Each probe ID received an annotation with respect to the gene from the corresponding platform annotation profile of the GDC website and the raw matrix data received the quantile normalization and log2 conversion. As smoking is the independent risk factor for HNSCC, we excluded the patients who smoked. HPV groupings for HNSCC patients were based on the HPV condition which provided by the Pan-Cancer Microbiome . 72 of the 249 remaining patients were HPV+ and 177 were HPV-. The raw gene expression datasets were processed. Samples with missing data were excluded from this study.The bulk RNA sequencing and the clinical data were obtained from the HNSCC dataset of TCGA database, which consisted of 487 samples  . The dathttps://github.com/CGATOxford/UMI-tools).Virus infected cells were defined with the Viral-Track approach  using one-class logistic regression machine-learning algorithm (OCLR). For the scRNA data, we employed the trajectory analysis using Monocle 2 package.GO ontology and KEGG pathway analyses were performed using the WebGestalt webserver. Cell- communication analyses was performed using the CellphoneDB R package . The Mon+ refers to the mean fluorescence intensity values above 1.5-fold negative control tissues.Primers were used to amplify the HPV 16 E6 region as follows: E6 forward primer, 5’-TCAGGACCCACAGGAGCG-3′, reverse primer, 5’-CCTCTCACGTCGCAGTAACTGTTG-3′. β-actin, which was used as housekeeping gene, was amplified by using forward primer 5’-TCACCCACACTGTGCCCATCTACGA-3′, reverse primer, 5’-CAGCGGAACCGCTCATTGCCAATGG-3′. HPVImmunofluorescence staining was performed as described previously . In brieAntibodies used for staining included: Mouse-anti-human CD3 monoclonal antibody , Rabbit-anti-human CTLA4 polyclonal antibody , Rabbit-anti-human PD1 polyclonal antibody , Rabbit-anti-human CCL4 polyclonal antibody , Rabbit-anti-human FGFR2 polyclonal antibody , A594 goat-anti-rabbit IgG , A488 donkey-anti-mouse IgG  and DAPI .Statistical studies were performed with the R software. Kaplan-Meier (KM) and receiver operating characteristic (ROC) tests were carried out as previously described –14, whic- patients when compared to those who were HPV+ . Kaplan-Meier curves showed shorter survival times for the HPV+ and HPV- tumour cells and GSEA functional analysis of these genes clearly indicated that HPV- tumour cells upregulated the genes associated with the IL17 signalling pathway  in HPV- tumour cells, despite the lack of significance in the data due to the small sample size  compared to HPV+ cells  showed a reduction in cytokine and chemokine signalling pathways  or as a result of HPV infection. HPV-associated HNSCC has been found to exhibit unique biologically and clinically relevant features, and patients with the virus show a survival advantage when compared to those without. However, due to the large number of HPV-independent HNSCC, there is the possibility that the prognostic differences seen between HPVstemness Figure 7+ tumours have a better prognosis compared to HPV- patients. The association of HPV with a better prognosis does not necessarily mean that HPV is not involved in the development of cancer. It is possible that negative cases were infected at an earlier time point before cancer diagnosis, and the fact that HPV negativity is usually associated with advanced tumours, suggests that these viruses may become undetectable at a later stage of the carcinogenic process , Guangxi Natural Science Foundation (#2020GXNSFAA259050) and Youjiang Medical University for Nationalities (#yy2019bsky001) and Research Program of The Affiliated Hospital of Youjiang Medical University for Nationalities (#R20212601).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The primary endpoint was the diagnosis of ED. Chi-square tests were used to analyze the distribution of demographic characteristics. The Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of ED in both groups, after adjusting for sex, age, relevant comorbidities, co-medication, and surgery. Results: ED developed in 181 patients of the study group. The incidence density of ED was 2.53 per 1000 person-years for the HPV group and 1.51 per 1000 person-years for the non-HPV group, with an adjusted HR (95% CI) of 1.63 (1.37–1.94). In stratification analysis, adjusted HR of diabetes-, chronic obstructive pulmonary disease (COPD-), and stroke-subgroup were 2.39, 2.51, and 4.82, with significant p values for interaction, respectively. Sensitivity analysis yields consistent findings. Conclusions: The patients with HPV infection had a higher risk of subsequent ED in comparison to the non-HPV controls. The mechanism behind such association and its possible role in ED prevention deserves further study in the future.Background: Male patients with genital warts are known for higher rates of sexual dysfunction. This study was conducted to investigate whether human papillomaviruses (HPV) infection is associated with an increased risk of erectile dysfunction (ED). Methods: Patients aged over 18 with HPV infection ( Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that infect the cutaneous and mucosa epithelium and are the most common sexually transmitted disease in women ,2. ThereEvidence suggests that males with genital warts have higher rates of sexual dysfunction . Among sChlamydia pneumoniae, cytomegalovirus, and hepatitis A virus infection can increase the risk of CAD, myocardial infarction, and even cardiovascular death [Previous studies propose that inflammation caused by viral ,38 or baar death ,47,48,49ar death . In addiar death , which mar death . The etiar death ,53,54.Given the fact that genital warts negatively affect male sexual function , the manThis study was constructed using longitudinal data from the National Health Insurance Research Database (NHIRD) in Taiwan. The NHIRD contains registry and original claimed data, such as the diagnoses coding, out-patient visits, hospitalization records, medication, and personal information of over 99% of Taiwan’s population. Quarterly expert reviews on randomly sampled claimed data, with a sampling rate of 1/50–100, were performed by the Bureau of National Health Insurance (BNHI). The BNHI also randomly reviews the medical charts of 1/100 ambulatory and 1/20 inpatient claims. This study was approved by the Institutional Review Board of the China Medical University Hospital Research Ethics Committee (CMUH104-REC2-115(AR-4)).2) laser operation, or chemosurgery for condyloma, as well as simple or complicated electrocauterization, liquid nitrogen cryosurgery, or cryotherapy using CO2 freezing or liquid nitrogen. All participants were followed up until the first medical record of ED or censored on the date of death, or the end of the study (31 December 2013). Finally, 13,296 subjects were included in the HPV group and 53,184 non-HPV subjects served as the control group.Participants with medical records of HPV infection  between 2000 and 2012 constituted the HPV group . The indThe primary endpoint of this study was set to be the diagnosis of ED (ICD-9-CM code 607.84 and 302.72) that recorded at least one inpatient or three outpatients , withdraTo eliminate potential bias, we adjusted for demographic variables, pre-existing co-morbidities and baseline co-medication, including hypertension (ICD-9-CM codes 401–405), diabetes mellitus (ICD-9-CM code 250), hyperlipidemia (ICD-9-CM code 272), stroke (ICD-9-CM code 430–438), coronary artery disease (ICD-9-CM code 410–414), chronic kidney disease (CKD) (ICD-9-CM code 585), chronic obstructive pulmonary disease (COPD) , alcohol-related illness , human immunodeficiency virus (HIV) infection , autoimmune disease (AID) including systemic lupus erythematosus (SLE) (ICD-9-CM code 710.0), rheumatoid arthritis (ICD-9-CM code 714.0), Sjögren’s syndrome (ICD-9-CM code 710.2), and multiple sclerosis (ICD-9-CM code 340). Other metrics that can affect ED were also adjusted in the analysis, including spinal cord injury pelvic fracture, burn of genitalia, foreign body entering through an orifice, injury to nerves and spinal cord, and poisoning. Information on comorbidities was obtained by tracing back 2 years before the index date about records of inpatients and ambulatory medical care in the database.The medication confounders analyzed in this study consist of alpha-blockers, beta-blockers, diuretics, and calcium channel blockers (CCBs). Drug use was defined as the use of a drug for more than three prescriptions (with each prescription for 28 days) from outpatient visits prior to the index date.Salmonella infection (NTS) was selected as the negative control exposure for its potential association with ischemic events [A negative control exposure was designated to examine potential external confounders ,58. One c events ,60. Howet-test. The incidence density of ED per 1000 person-years was calculated in both groups. Multivariable Cox proportional hazards regression models were utilized to estimate the crude hazard ratios (cHRs), adjusted HRs (aHRs), and 95% confidence intervals (CIs) of ED for the HPV group versus the non-HPV group. The covariates adopted in the multivariate models encompassed sex, age, co-morbidities, and co-medications listed in p-value of <0.05.Chi-squared tests were applied to compare the distribution of age, sex, and baseline co-morbidities between the HPV and non-HPV groups. The age mean was compared using Student’s We performed a sensitivity analysis excluding patients with cancer and stroke at the index date to examine whether our findings remain constant under different assumptions.We enrolled 13,296 patients newly diagnosed with an HPV infection from 2000 to 2012 and 53,184 non-HPV controls in this study. The baseline characteristics of patients with and without an HPV infection were not significantly different, as all standard mean differences between the groups were <0.1 . The meap < 0.001). p < 0.001; details in In Negative control analysis showed that there was no association between NTS and subsequent ED with aHR, 0.69; 95% CI 0.31–1.53 (detail in p < 0.001)  .p-value for the interaction of age was not significant (p = 0.4). In comorbidities-subgroup analysis, among participants with diabetes, there was a positive association between HPV infection with ED . Such positive association was also found among patients with stroke , and COPD  with p values for interaction 0.001 and 0.03, respectively.In In this large-scale population-based cohort study with up to 14 years of follow-up, we reported that individuals with HPV infection had a higher risk of developing ED. We selected symptomatic HPV patients as the study population because both inpatients and outpatients with symptoms are rarely studied. The subgroup analyses indicated that HPV-infected patients had a significantly higher risk of ED if they had a stroke or COPD. That is, COPD and stroke acted as modifiers for the relationship between HPV infection and ED. COPD is a consequence of tobacco use which is a well-known risk for ED. A time-to-event analysis indicated a positive association between HPV infection and ED in all the follow-up periods, which may be due to the characteristic of recurrent HPV infection . HoweverPrevious studies on HPV infection have reported that women of reproductive age with positive HPV tests for cervical screening have poorer sexual function . On the In this cohort study, we employed a nationwide population-based registry to provide epidemiological evidence on the risks of new-onset ED in patients with HPV infection. The effect of measurable confounders was minimized by PS matching ,73,74,75However, there are several limitations to this study. First, the evaluation of HPV infection is challenging, as many infections might not be clinically recognized ,77,78. TFindings of this cohort study suggest that ED is an overlooked long-term complication of HPV infections in males. Future studies on HPV infections in males are warranted to facilitate the diagnosis and management of HPV infections.


Single-dose HPV vaccination, if efficacious, would be tremendouslyadvantageous; simplifying implementation and decreasing costs.We performed a randomized, multi-center, double-blind, controlledtrial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) or bivalent(HPV 16/18) HPV vaccination compared to meningococcal vaccination amongKenyan women aged 15-20 years. Enrollment and six monthly cervical swabs anda month three vaginal swab were tested for HPV DNA. Enrollment sera weretested for HPV antibodies. The modified intent-to-treat (mITT) cohortcomprised participants who tested HPV antibody negative at enrollment andHPV DNA negative at enrollment and month three. The primary outcome wasincident persistent vaccine-type HPV infection by month 18.Between December 2018 and June 2021, 2,275 women were randomlyassigned and followed; 758 received the nonavalent HPV vaccine, 760 thebivalent HPV vaccine, and 757 the meningococcal vaccine; retention was 98%.Thirty-eight incident persistent infections were detected in the HPV 16/18mITT cohort: one each among participants assigned to the bivalent andnonavalent groups and 36 among those assigned to the meningococcal group;nonavalent Vaccine Efficacy (VE) was 97.5% , and bivalent VE was 97.5% . Thirty-three incident persistent infections were detectedin the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent groupand 29 in the meningococcal group; nonavalent VE for HPV16/18/31/33/45/52/58 was 88.9% . The rateof SAEs was 4.5-5.2% by group.Over the 18 month time-frame we studied, single-dose bivalent andnonavalent HPV vaccines were each highly effective in preventing incidentpersistent oncogenic HPV infection, similar to multidose regimens. Currently, four HPV vaccines arelicensed, all targeting high-risk (oncogenic) HPV types that cause 70% of cancers(HPV 16/18) and two also targeting low-risk HPV types that cause genital warts (HPV6/11); the bivalent vaccine (Cervarix® and Cecolin®) prevents HPV16/18 infection, the quadrivalent vaccine (Gardasil®) prevents HPV16/18/6/11, and the nonavalent vaccine (Gardasil-9®) prevents HPV16/18/31/33/45/52/58/6/11 infection .14 In Kenya, multidose HPV vaccination isoffered to 9-14-year-old girls through the national immunization program fromOctober 2019; however, due to supply constraints, HPV vaccination was offered to10-year-old girls only. To date, an estimated 10% of 10 year old girls have receivedtheir first HPV vaccine dose and 3% have received the second dose.15 Catch-up vaccination foradolescent girls and young women 15 years of age and older is not provided, withcervical cancer screening offered to older women. Testing the efficacy ofsingle-dose HPV vaccination among young women age 15 years and older, within thecontext of cytological screening for dysplastic lesions in a clinical trial, wasdetermined to be ethical as vaccination for this age group in Kenya and many LMICsis not currently supported through national programs or global immunization bodies.Specifically, we evaluated zero versus single-dose HPV vaccination against thebackdrop of substantial disparities in cervical cancer incidence.16 Also, a superiority design waschosen, compared to a non-inferiority design, as the smaller sample size and shortertime line would support robust, feasible, and timely evidence. Here we report thefindings of an efficacy trial of single-dose bivalent and nonavalent HPV vaccinationamong young women in Kenya.Observational studies suggest that single-dose HPV vaccine effectiveness isequivalent to a two- or three-dose regimen: however, vaccination guidelinesrecommend multidose strategies and questions persist regarding single-doseefficacy.17 Kenya’s HPV National ImmunizationProgram, launched in October 2019, offers two doses of the quadrivalent HPVvaccine to 9-10-year-old girls and is not provided through the NationalImmunization Program for persons aged 15 years and older; meningococcalvaccination is used during outbreaks.18 Meningococcal vaccination was chosen as the comparatorbecause meningococcal antibodies offer potential clinical benefits and do notimpact HPV outcomes. Participants were randomized to 1) immediate nonavalent HPVvaccination and delayed (36 months after enrollment) meningococcal vaccination,2) immediate bivalent HPV vaccination and delayed meningococcal vaccination, or3) immediate meningococcal vaccination and delayed HPV vaccination. The primaryanalysis was planned for month 18, with the final analysis at month 36evaluating durability (not reported herein). At this time the trial is ongoing.After the 18 month results presented herein, we are continuing follow-up in ablinded cross-over design to evaluate vaccine durability.This randomized, multi-center, double-blind, parallel, three-armcontrolled, superiority trial tested the efficacy of single-dose bivalent (HPV16/18) and single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPVvaccination, as described in the published protocol paper.ClinicalTrials.gov (NCT03675256).The Kenya Medical Research Institute (KEMRI) Scientific and Ethics ReviewUnit (SERU) and the University of Washington (UW) Institutional Review Board(IRB) approved the study. The study was registered with Participants were recruited through community outreach. Participantswere eligible for randomization if they were able to provide informed consent,age 15 to 20 years old, female sex assigned at birth, sexually active reportingone to five lifetime partners, and resident within the study area. Studyexclusion criteria were a positive HIV diagnostic test, history of HPVvaccination, allergies to vaccine components or latex, current pregnancy,hysterectomy, or history of immunosuppressive conditions.The study was conducted at three KEMRI clinical sites in Thika, Nairobi,and Kisumu. All participants, and their parents/guardians in the case of minors,provided informed consent, which included counseling about randomization, risksand benefits of participation, study procedures, and their rights as researchparticipants.Potential participants completed eligibility screening with a providerincluding a detailed medical history, collection of external genital and cervical swabs for HPV deoxyribonucleic acid (DNA)testing, and serum for HPV antibody testing. Participants received cytologicalcervical cancer screening at enrollment. Sexual and reproductive health services were offered at enrollment and every visit. Allquestionnaires were conducted using electronic case report forms .http://www.randomize.net . An unblinded pharmacist entered the participant identification numberon randomize.net, obtained the next sequentialintervention assignment, recorded the participant identification number andrandomization identifier on an electronic case report form, drew up the vaccinein a masked syringe, and administered the vaccination.Randomization was stratified by site, using a fixed block size of 15,and a 1:1:1 allocation. Study staff, participants, investigators, clinic staff,lab technicians, and other study team members did not have access to therandomization codes, except for the unblinded statistical analysts and unblindedpharmacists at each site. Blinded study assignment was implemented via 19 wereavailable at subsequent follow-up visits by participant choice or to comply withCOVID-19 research restrictions.Participants were seen at months three, six, and then every six monthsfor 18 months after enrollment. Providers administered clinical questionnairesand collected a cervical swab at each six-month visit. Participantsself-collected vaginal swabs using validated instructions at month three;self-collected swabs, which have similar accuracy compared to provider collectedcervical swabs,21 at the UWEast Africa STI Laboratory, Mombasa, Kenya with standard proficiencytesting.22 ForHPV-positive samples, a low (+), intermediate (++), or high (+++) positivity wasindicated; + or greater were considered positive. All runs included negative andpositive controls, and the housekeeping human gene, β-globin, as aninternal control. Runs were performed with CFX96 Real-time PCR System .HPV DNA genotyping was conducted using the Anyplex II HPV28 assay, a multiplexed type-specific real-time polymerasechain reaction (PCR) based assay24 The mean pre-established fluorescent intensity (MFI)seropositivity cutoffs for HPV 16/18/31/33/45/52/58 were used were assessed by nucleic acid amplification testing  at the University of Washington-University of Nairobi East AfricaSTI Laboratory; HSV-2 was evaluated by the Focus ELISA and bacterial vaginosiswas evaluated using the Nugent Score.Sexually transmitted infections  to match the analysis cohort for HPV vaccine licensure trials. Theextended sensitivity cohort analysis used all available data, including visitsafter the pre-specified month 18 data cut. Safety was assessed through adverseevent reporting following the United States National Institute of Allergy andInfectious Diseases guidelines.25The primary trial endpoint was incident persistent cervical HPVinfection among participants who tested HPV DNA negative  at enrollment and month three  andHPV antibody negative at enrollment (the modified intent-to-treat (mITT)cohort). For inclusion in the HPV 16/18 mITT cohort, participants were HPV 16/18naïve. Similarly, for the HPV 16/18/31/33/45/52/58 mITT cohort,participants were HPV 16/18/31/33/45/52/58 naïve. Persistent HPV, asurrogate marker for cervical dysplasia/precancer, was defined as high-riskvaccine type specific HPV  detected at two consecutivetime points no less than four months apart after month three and up to andincluding month 18 (same HPV type at both time points) for the primaryanalysis.26 The sample size calculations also assumed a combinedpersistent HPV 16/18/31/33/45/52/58 annual incidence of 5%, single-dose vaccineefficacy of 75%, and loss-to-follow-up of 10% with a fixed follow-up time of 12months. Assuming a proportional hazards model (seqDesign in R) with 80% power todetect 75% efficacy, a sample size of 2250 participants was planned.Sample size calculations assumed that 52% of participants would meetrequirements for inclusion in the mITT cohort based on the observed prevalenceof HPV infection in similar settings.We used Cox proportional hazards (PH) models stratified by site toestimate the hazard ratios (HRs) of the interventions versus control for theprimary and sensitivity analyses. Models for the sensitivity analyses used crudeincidence rate ratios instead of Cox when no events were observed in a group.Follow-up was calculated as days since the month three visit for the primaryanalysis, and days since month six for the extended sensitivity analysis.Participants who did not reach the efficacy endpoints were censored at the timeof the last negative test at or before the month 18 visit. Vaccine efficacy wasexpressed as a 1 minus the hazard ratio (or relative risk). The log-rank teststratified by site was used to calculate the p-value. Cumulative incidenceKaplan-Meier curves of time to infection were calculated by intervention group.Efficacy analyses were performed on the month 18 mITT cohorts. In post-hocanalysis, we evaluated the absolute difference in cumulative incidence of HPVfrom the Kaplan-Meier curves at month 18. We calculated the cumulative incidenceof chlamydia and gonorrhea during follow-up by assigned group.Safety was assessed among all participants; the three groups werecompared using Fisher’s exact test. We performed all analyses using SASsoftware, version 9.2  and double coded in R(version 4.1).An independent Data Safety and Monitoring Board (DSMB) was constitutedto review study progress, participant safety, and the primary outcome; the DSMBmet annually.th, 2018, and November 15th,2019, 3,090 participants were screened for study eligibility and 2,275 (74%)were enrolled. Of those ineligible, 132 (16%) had a positive pregnancy test, 51(6%) declined study procedures, 34 (4%) had a positive rapid HIV test, and 172(21%) met other exclusion criteria. Enrolled participants were randomized , or hadmissing antibody results (n=1) or a missing month three swab (n=155) wereexcluded. Among the 1,458 participants meeting criteria for the primary HPV16/18 mITT analysis, 496 were in the nonavalent, 489 in the bivalent, and 473 inthe meningococcal group. For HPV 16/18/31/33/45/52/58, participants who testedHPV 16/18/31/33/45/52/58 antibody or HPV 16/18/31/33/45/52/58 DNA positive atenrollment or HPV DNA positive at month three (n=792) or had missing antibodyresults (n=1) or a missing month three swab (n=106) were excluded. Of the 615participants eligible for the primary HPV 16/18/31/33/45/52/58 analysis, 325were in the nonavalent and 290 in the meningococcal vaccine group. Oneparticipant in the meningococcal vaccine group did not have at least onepost-month three endpoint swab. The median age was 17 years for the HPV 16/18and HPV 16/18/31/33/45/52/58 mITT cohorts ; and, overall, the baselinecharacteristics by study groups were comparable  and S27.One hundred percent of participants received their assigned vaccine,without administration error. By the month 18 visit, retention for assessment ofthe primary endpoints was 98% for two swabs and 94% for three swabs; 94% ofswabs were cervical swabs and 6% of swabs were self-collected vaginal swabs-8, S13. A total of 38 incident persistent infections were detected in the HPV16/18 mITT cohort: one each among participants assigned to the bivalent andnonavalent vaccine groups and 36 among those assigned to the meningococcalvaccine group . The incIn the extended sensitivity analysis, there were a total of 16 incidentpersistent infections in the HPV 16/18 mITT cohort: 0 each among participantsassigned to the bivalent and nonavalent vaccine groups and 16 among thoseassigned to the meningococcal vaccine group . HPV 16/post-hoc analysis, using only provider collectedendpoint cervical swabs and excluding self-collected vaginal swabs, the resultsfor the primary analysis were not different: the VE was 97.3% (95% CI 80.0-99.6%) for each of the bivalent and nonavalent vaccines in the HPV 16/18 mITTcohort. Nonavalent vaccine efficacy was 91.4% (95% CI 71.8-97.4%) in the HPV16/18/31/33/45/52/58 mITT cohort  for both the bivalentand nonavalent vaccines; an absolute incidence of 0.2% (95% CI 0.0 –0.6%) in the bivalent and nonavalent vaccine groups compared to 7.9% (95% CI 5.4– 10.4%) in the meningococcal group. For the HPV 16/18/31/33/45/52/58mITT cohort, the absolute reduction in persistent HPV 16/18/31/33/45/52/58infection was −9.3% (95% CI −13.6 – −5.1%) for thenonavalent vaccine; an absolute incidence of 1.3% (95% CI 0.0 – 2.5%) inthe nonavalent vaccine group compared to 10.6% (95% CI 6.9 – 14.2%) inthe meningococcal group.In There were 112 participants who experienced serious adverse events(SAEs), which included 57 participants with pregnancy-related SAEs, 46 withinfections or inflammatory conditions , seveninjuries, and five mental health illnesses. Overall, the frequency was similarbetween groups . There w27 The high level ofefficacy builds on observational data12 and provides,should the effect be sustained, evidence for single-dose HPV vaccination to preventpersistent HPV infections, which could increase vaccine access and coverage,offering a cost-effective strategy for cervical cancer prevention.28Over the 18 months of this trial, the efficacy of single-dose bivalent ornonavalent HPV vaccine was very high among Kenyan adolescent girls and young women,demonstrating high levels of protection against vaccine-specific oncogenic HPVinfection. Protection against HPV 16/18 infection was 97.5% for both vaccines;together with observed high reductions in the absolute cumulative incidence thissuggests, should the protection have a durable effect, the potential for publichealth impact in the context of disparities in outcomes for cervical cancer casesand deaths .SalientStrengths of the study include the randomized, double-blind, controlleddesign, high retention, measurement of cervical HPV DNA as the outcome,determination of persistent HPV DNA, and the head-to-head comparison of the licensedbivalent and nonavalent HPV vaccines in protection against persistent infection withoncogenic HPV types included in the vaccines. In addition, the trial successfullyenrolled persons exposed to HPV infection who were successfully retained in allrandomized groups, allowing rapid assessment of single-dose efficacy.11Following these results, participants will receive blinded cross-over29 vaccination, ensuring all receiveHPV vaccination, with an additional 18 months follow-up to evaluate single-dosedurability, and access to the second dose following guidelines. The blindedcross-over design will allow us to calculate the durability of the vaccine efficacydemonstrated to date. Second, the proportion of randomized participants who werenaive to HPV 16/18/31/33/45/52/58 was lower than expected (~40%) potentiallydecreasing the study power; however, incidence was higher than assumed and theefficacy result is statistically significant. Third, 6% of primary endpoint swabswere self-collected, and 94% were provider collected. Ideally, collection would beidentical; however, the correlation between self-collected vaginal and providercollected cervical swabs is high19and there was no difference in the results when self-collected swabs were excluded.An additional concern is whether antibody levels were declining over the observationperiod such that the high efficacy initially observed would be sustained. However,in a study conducted in India over ten years duration, antibody levels at plateauwere such that vaccine efficacy is high (>95%)11 suggesting that even higher antibody levelscould only demonstrate a small further increase in vaccine efficacy. In addition,the plateau level for single-dose HPV vaccination is reached by month 12.30 Lastly, while the GST-ELISAmultiplex assay used to exclude participants with HPV antibodies at enrollmentdemonstrated overall agreement of 89% with the gold standard secreted alkalinephosphatase pseudovirion based neutralization assay,31 misclassification of participants asantibody naïve would not be different by study group. Further in sensitivityanalysis including participants with HPV antibodies at baseline, overall vaccineefficacy was in keeping with the primary findings (We acknowledge that the study has limitations. First, the duration offollow-up is 18 months and the durability of single-dose vaccine efficacy remains tobe demonstrated. However, observational data for single-dose HPV vaccinationsupports efficacy over a decade.findings  and S24.33 Cervical cancer is almost entirelypreventable through HPV vaccination. If the effects of single-dose HPV vaccinationare durable, as we have reason to believe they will be, this approach could serve toclose the gap between the WHO’s goal of 90% HPV vaccination coverage by 2030and the 15% of girls globally currently vaccinated,34alleviate vaccine supply constraints,35 and provide global policy makers with options to allocateexisting HPV vaccine supply.Cervical cancer is the fourth most common cancer among women globally, thesecond most frequent in sub-Saharan Africa and primarily affects women between ages30-49 years and is the leading cause of cancer deaths in sub-SaharanAfrica.Supplement


To undertake a content analysis of human papillomavirus (HPV) vaccine communication materials available to young people.Content analysis.Majority English-speaking countries.Between March and April 2020, a web engine was utilised to search for and retrieve relevant communication materials. Content analysis was used to describe how the following key issues were covered: (1) side effects, (2) safety, (3) practicalities related to receiving the HPV vaccine and (4) gender-specific information.A total of 44 separate communication materials were retrieved, predominantly videos, webpages and leaflets. There was a focus on mild side effects of the vaccine (43.2%), with less frequent reference being made to moderate or serious side effects (22.7%). Reassurance concerning the safety profile of vaccine was communicated by referencing the widespread use of the HPV vaccine (31.8%). Information regarding formal criteria for entry into the vaccination programme emphasised country-specific eligibility criteria (59.1%), the setting in which vaccination was offered (38.6%) and the number of doses required (38.6%). Content intended to improve young people’s experiences of receiving the HPV vaccine was less often provided (22.7%). Gender-specific content usually related to specific HPV-related diseases (52.3%) and/or the availability of cervical cancer screening programmes (52.3%).A variety of different communication tools were retrieved encompassing a wide variety of formats and content, reflective of different vaccination programmes and the varied priorities of organisations producing the materials. Findings will inform the co-production of a tailored educational package to improve access to information by populations of young people identified as having lower HPV vaccine uptake. Three human papillomavirus (HPV) vaccines have been licenced globally around the world – bivalent, quadrivalent and nonvalent vaccines. If administered before sexual debut, these vaccines offer protection against high-risk HPV types 16 and 18, which are responsible for approximately 70% of cases of cervical cancer, and other cancers affecting the vulva, vagina, penis, anus and oral cavity .The Communication about the English HPV vaccination programme usually comprises information leaflets, together with paper-based or electronic forms requesting parental consent, which are distributed through the school to parents or carers. Immunisation teams may also deliver educational sessions to parents and young people in the school setting, although this is not consistently implemented across all areas. Paper-based information leaflets and parental consent forms may be taken home by the vaccine-eligible students for discussion with their parents , 2020b. HPV vaccination programmes are increasingly being delivered to young men and in 2019, the English HPV vaccination programme was expanded to be offered to young men aged 12–13 years old following recommendations from the Globally, there is increasing recognition that vaccine hesitancy, delays in accepting vaccination or refusal of vaccines despite the availability of vaccination services contribute to lower uptake . Lower vExisting measures, including the 5C scale , the VacImproving the communication of evidence-based vaccine messages and responding to misinformation circulating in social media and anti-vaccination activities have been proposed as strategies to address vaccine hesitancy and improve vaccine confidence .An effective communication strategy may change how young people and their parents think and feel about the HPV vaccine, leading to higher and more equitable uptake. While knowledge is recognised as important, information provision alone may not change health behaviour. Information materials, be these paper-based or digital, need to be tailored to target populations if uptake is to be improved . As partA systematic review concluded there was no strong evidence to recommend any specific educational intervention for wide-spread implementation to increase HPV vaccination acceptance . HoweverThe EDUCATE study aims to co-produce an educational package about the HPV vaccine with young people for delivery in schools . The pacThe overall aim of the content analysis was to examine and summarise available HPV vaccine communication materials  for young people in majority English-speaking countries. The specific objectives were to(i) Undertake searches using a Web search engine to locate online HPV vaccine communication materials targeted at young people in English-speaking countries;(ii) Describe the characteristics, format and content of the communication materials; and(iii) Inform the development of an HPV vaccine communication tool as part of the EDUCATE co-production study with young people.HPV vaccine communication materials were eligible for inclusion if they met the following criteria: (1) available in a majority English-speaking country according to the Searches and retrieval of HPV vaccine communication materials were undertaken between 20 March and 16 April 2020 by entering a combination of the following text words into the Google search engine, alongside the name of each majority English-speaking country: ‘HPV vaccine’, ‘information’ and ‘young people’. The search was not intended to be exhaustive but aimed to identify information easily accessible to the target audience of young people. Further searches were undertaken to identify information not available through the initial searches, by accessing websites of international organisations known to the lead researcher.Descriptive information  about the communication materials, and the HPV vaccination programmes they related to, were collated in an Excel spreadsheet.Content analysis is a research tool used to quantify and analyse the presence of key words, themes or concepts within qualitative data. The lead author (H.F.) independently coded the communication materials using both deductive (pre-defined criteria) and inductive (arising from the data) methods to code the content of the communication materials. Coding by one researcher was considered sufficient as the purpose of this analysis was simply to flag the presence or absence of content which required minimal interpretation of the data.The content of the communication materials was initially coded using pre-defined deductive criteria relating to (1) side effects, (2) safety and (3) formal criteria for the vaccination programme. These criteria were guided by the findings from previous research related to this study which documented written reasons for refusal of the HPV vaccine by parents, including concerns related to safety and side effects (data available from first author on request). As coding progressed, a further category ‘gender-specific’ was inductively developed for text that was not universal to both genders . A brief description of the format and imagery used in the communication materials was also recorded.Once coding had been completed, the process was shared with co-author (T.C.) to provide feedback and analytical rigour. The findings were discussed during research team meetings with any disagreements in coding reconciled verbally. The frequency with which content occurred, assessed by the number of communication materials from which the content had been extracted, was calculated with the aid of NVivo software (v.12).A summary of the characteristics of the 44 HPV vaccine communication materials retrieved is provided .Of the 22 countries defined as majority English-speaking, communication materials relating to HPV vaccination programmes were retrieved for 8 (36.4%) countries. These were Australia, Canada, New Zealand, USA and the four countries within the UK: England, Northern Ireland, Scotland and Wales.Notably, no communication materials were retrieved for English-speaking countries in the Caribbean, where HPV vaccination programmes have been introduced in recent years.n = 18, 40.9%). Within this category, there were communication materials specific to the English , Welsh  and Scottish  programmes, but none for the programme in Northern Ireland. Other communication materials were specific to Australia , Canada , New Zealand  and the USA . The remaining communication materials were more broadly targeting international audiences .A large proportion of the communication materials retrieved were in relation to HPV vaccination programmes delivered in the UK (Fifteen (34.1%) of the 44 communication materials were also available in languages other than English. One international website provided 11 different communication materials  translated into French, Hindi, Malay, Spanish and Chinese. A video was provided in Te Reo, spoken by the Māori people, for the New Zealand HPV vaccination programme. For the Scottish HPV vaccination programme, an information leaflet was provided in Polish, Arabic and simplified Chinese. A poster to advertise the Welsh vaccination programme was produced as a bilingual document in English and Welsh. Finally, a webpage for the US HPV vaccination programme was available in Spanish.n = 18, 40.9%), webpages , leaflets , factsheets , posters , PowerPoint presentations for lessons in school  and a booklet .The communication materials were available in the following formats: video , cartoon images , clip art , photos  and videos  (Thirty-one of the 44 (70.5%) communication materials used at least one type of imagery to support the communication of HPV vaccine messages. Types of media included animation  .n = 10, 22.7%), community settings  and immunisation sessions . Health care settings were not shown. Over one-quarter of images of young people showed mixed sex groups , and the same proportion included images of young people from different ethnic groups . Two (4.5%) communication materials were illustrated with single-sex participants. Some showed young people wearing school uniform . Immunisation nurses were represented less frequently within communication materials   .n = 43, 97.7%), followed by gender-specific content , safety  and side effects   . Furthern = 26, 59.1%), vaccination schedule (e.g. number of doses and timing) , setting of vaccination , information about decision-making and consent , whether the vaccine was provided free of charge  and procedures to access missed doses .Country-specific information about the HPV vaccination programmes included eligibility criteria (e.g. age) , describing the site of vaccination (e.g. upper arm), the sensation related to having the vaccine and who would administer the vaccine. Suggestions were also provided to improve young people’s experiences . Advice included distraction methods while receiving the vaccine, avoiding heavy exercise and ensuring adequate nutrition. Infrequently, communication materials included young people discussing their own experience of having the vaccine .Some communication materials provided information intended to prepare young people for receiving the vaccination . Some materials provided information related to the frequency of HPV-related disease within a particular country . The availability of, and requirement for, cervical cancer screening and HPV testing for women was also referenced .The most common content specific to gender related to HPV-related diseases that affect men and women . Only three (6.8%) communication materials presented content related to sexual orientation and gender identity, such as higher risk of HPV acquisition among men who have sex with men , and eligibility for the vaccine among transgender populations or men who have sex with men.Reflecting recent policy changes to expand the programme to include young men, some communication materials emphasised the HPV vaccine was provided to both sexes . Some materials also referenced evidence from pre-vaccine licensure trials  and gave details on the role of national and international committees in monitoring vaccine safety data .Evidence of vaccine safety was communicated most frequently by referencing the wide use of the vaccine (e.g. the cumulative number of doses provided worldwide or within a specific country) . Signposting to websites with further information related to vaccine safety was less common . Reference to regulatory procedures for the introduction of medical devices was less frequently used to support vaccine safety . Five communication materials (11.4%) simply referred to the HPV vaccine as being safe, without providing evidence to support the statement.Some communication materials provided content which specifically refuted associations with the development of long-term health conditions (e.g. chronic fatigue syndrome)  emphasised the likelihood of experiencing mild side effects . Information relating to the occurrence of moderate to severe side effects  was provided less frequently . Two communication materials (4.5%) provided specific data related to the anticipated frequency of side effects .All communication materials that reported on side effects . Some communication materials directed the target audience to websites containing further information about side effects .Other content which aimed to reassure the target audience about safety included describing procedures for responding to side effects  (This study provides an overview of the characteristics of communication materials for young people, comprising a variety of formats and content, reflective of different priorities of organisations producing the materials and vaccination programmes which they referred to.The content analysis was undertaken to inform the co-production of an educational package relevant to young people that aims to address their information needs about the HPV vaccine. This included developing the topic guides to be used in the EDUCATE study to gather information from young people and professionals during preliminary interviews about their preferences for content in relation to the risk of HPV acquisition, HPV-related disease, the benefits of vaccination, vaccine safety and side effects, and the vaccination process. At a later stage of the study, young people’s opinions on the form and content of a selection of the communication materials will be obtained during workshops. Together, these findings will be used to inform the co-production of communication materials with young people as part of the EDUCATE study .Lack of knowledge about the HPV vaccine has been demonstrated especially among some male populations , reflectMen who have sex with men are at heightened risk of developing HPV-related disease and, in some countries, the national HPV vaccination programme has been extended to men who have sex with men for older ages. For example, since 2018 in England, the HPV vaccine has been available through sexual health services or HIV clinics for men who have sex with men for any age up 45 years . HoweverAs is common practice for other drugs and medical procedures, information was given about the safety of vaccination and possible side effects. This is relevant to previous research which has shown that families are concerned about, and value the provision of information about, the safety and side effects of the HPV vaccine . HoweverSchool-based educational interventions have been shown to be effective at increasing uptake of, and knowledge about, the HPV vaccine . Uptake There is emerging evidence to support the value of social media campaigns to address misinformation among parents and adult women . HoweverIn order to improve communication about the HPV vaccine, interventions should be developed with, and tailored by, the target populations with lower uptake. This is important to ensure messages are framed in a way that is most likely to address vaccine hesitancy and enable positive decision-making. Calls have been made for the provision of evidence-based education that is comprehensive and resonates with what young people want . ThroughLower knowledge  and uptaOur search strategy was not exhaustive, and we focussed only on countries where English is defined as the majority language. We relied on Internet searching to uncover HPV vaccination materials meeting the study criteria, and did not contact official bodies to identify whether additional communication materials were available as we wanted to ensure the documents included were easily accessible by young people while undertaking the research. Therefore, our findings are unlikely to be representative of countries where the Internet is not a major way in which health-related information is communicated or where English is not widely spoken.We had originally intended to collect information related to literacy proofing or evidence of use of straightforward, easy to understand language appropriate for the target population. However, this was not reported or not possible to ascertain for this study. Therefore, it is unknown whether any of the communication materials included in this study had been developed specifically for populations with lower levels of literacy.Providing young people with opportunities to develop health care decision-making skills and improve their health literacy is a key part of the transition from adolescence to adulthood. We found that a variety of communication materials were available for young people. These encompassed different formats and content, reflective of the HPV vaccination programmes and priorities of organisations producing the materials. More needs to be done however to tailor communication materials to address the specific information needs, improve health literacy and address vaccine hesitancy among populations identified as having a lower uptake of HPV vaccination programmes. Findings from this content analysis are being used to inform the EDUCATE study, which will test the most appropriate ways of developing and communicating key information about the HPV vaccine to young people in a way that is accessible and relevant.