bluuebunny/crossref_metadata_2025 huggingface dataset:
P327 Comparison of adalimumab drug levels and drug survival in proactive vs reactive therapeutic drug monitoring
Authors: Shields S , Dunlop A , Barry S , Galloway P , Seenan J P , Macdonald J
Published: January 2022

Background

The therapeutic landscape for inflammatory bowel disease (IBD) has expanded in recent years. The anti-TNF drug adalimumab remains one of the most commonly prescribed treatments. However, rates of loss of response to adalimumab are significant. Therapeutic Drug Monitoring (TDM) has emerged as a tool to prevent loss of response to treatment but there is no consensus on the optimum TDM testing strategy., 2 testing strategies are commonly used - proactive TDM (pTDM), performed during sustained clinical response and reactive TDM (rTDM), performed following loss of response. The aim of this work was to compare adalimumab drug levels (DL) and drug survival (DS) for patients exposed to pTDM compared to rTDM testing strategies.

Methods

Data for patients with IBD, treated with adalimumab, and exposed to TDM, was extracted from the Scottish Biologic TDM database. Patients were assigned to pTDM or rTDM groups based on the indication of their first TDM test. Prescribing information was extracted from the NHS Scotland Safe Haven homecare prescribing database. Homecare delivery dates were used to infer start and end dates of adalimumab treatment. Where adalimumab start date was before, 2017, a start date of, 1/1/2017 was used to coincide with the introduction of the Scottish TDM service. The study period was, 1/1/2017 to, 1/3/2020 giving a maximum duration of drug exposure of, 38 months. The most recent drug level was used for each patient to reflect the impact of the TDM strategy employed. SPSS was used to perform statistical analysis.

Results

367 patients were included for analysis, 190 males and, 177 females, 262 with Crohn’s disease and, 105 with Ulcerative Colitis., 314 patients were assigned to the pTDM group, and, 53 to the rTDM group. The mean DL across both groups was, 9.5 mcg/ml, with no significant difference seen between pTDM and rTDM groups (p=0.642). Median DS in the pTDM group was, 21 months versus, 15.6 months in the rTDM group. 277 patients (75.5%) remained on treatment at the end of the study, 244 (77.7%) in the pTDM group, versus, 33 (62.3%) in the rTDM group. DS was significantly higher in the pTDM group compared to the rTDM (p=0.004) group (Fig., 1), with divergence of the survival curve seen after, 6 months.

Conclusion

pTDM has been clearly favoured by clinicians from the outset of the TDM service. Whilst our data shows that DLs do not vary significantly between TDM groups, importantly, the DS with adalimumab is longer with pTDM as part of routine clinical care, when compared to rTDM. Further evaluation of clinical outcomes including steroid prescription, hospital admissions and surgery rates in the context of pTDM and rTDM strategies is therefore warranted, and in progress.
P369 Dual Biologic in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series
Authors: Wlazło M , Jarzębicka D , Meglicka M , Kierkuś J
Published: January 2022

Background

Inflammatory bowel diseases (IBD) patients equipped in biological therapy embody a group with significant disease burden who have never succeeded conventional medication such as corticosteroids and thiopurines. Biologic agents are frequently used in the disease course, however they only result in, 1-year remission rates of approximately, 40% in given IBD populations. We aim to assess the efficacy and safety of concomitant use of, 2 biologic therapies including: anti-TNF (infliksimab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort.

Methods

Eight children (5 ulcerative colitis, 1 ulcerative colitis/IBD-unspecified, 2 Crohn’s disease) with a disease duration of, 3,2 (8mth-9 years), initiated dual therapy at an age of, 10,8 (3–17) years after failing ≥2 biologic therapies. Three (37,5%) were treated with ustekinumab/adalimumab, 3 (37,5%) with vedolizumab/adalimumab and, 2 (25%) with infliksimab/vedolizumab. Primary outcome was clinical response after minimum, 3 dose of a second biological drug. It was defined as a decrease in PCDAI of at least, 12.5 points between baseline and, 3th dose of a second biological drug for CD, and a decrease in PUCAI of at least, 20 points between baseline and this time for UC.

Results

A clinical improvement was obtained in seven children (87,5%;, 4 UC, 1 UC/IBD-unspecified, 2 CD) in PCDAI/PUCAI scale after minimum, 3 dose of a second biological drug. Clinical response in patients: mean baseline PCDAI score was, 58,5 ±, 9 and, 21 ±, 19 after induction therapy with second biological drug, while PUCAI score was, 62 ±, 17 vs., 29 ±, 15, respectively. We reported one adverse event during treatment in the form of an anal abscess (UC, vedolizumab/adalimumab).

Conclusion

In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The application of dual biological therapy seems to be an appealing therapeutic option and may bring a possibility to better tailor and customize the therapies for patients. In a few publications the comparative efficacy and safety endpoints of dual therapies have been provided. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies such as randomized control trials are needed.
P380 Early improvement of endoscopic outcomes with risankizumab is associated with reduced hospitalisation and surgery rates in patients with Crohn’s disease
Authors: Feagan B G , Colombel J F , Panaccione R , Schreiber S , Ferrante M , Kamikozuru K , Lee W J , Griffith J , Kligys K , Kalabic J , Chen N , Dubinsky M
Published: January 2022

Background

Control of endoscopic inflammation like endoscopic remission is an important treatment target in Crohn’s disease (CD), as suggested in the STRIDE II guidelines. This study evaluated the relationship of early improvement in endoscopic outcomes on hospitalisation and surgery rates at, 52 wks in patients with CD treated with risankizumab (RZB).

Methods

This post-hoc analysis uses data from three double-blind, randomised Phase, 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials evaluating the efficacy and safety of RZB in patients with moderate to severe CD. Patients who responded to, 12-wk induction therapy with RZB IV (600 mg or, 1200mg) in ADVANCE or MOTIVATE and received up to, 52 wks of maintenance therapy with RZB SC (180 mg or, 360 mg) in FORTIFY were analysed. Incidence rates (events/100 person-years) of CD-related hospitalisation, CD-related surgery (surgical procedures due to adverse events or complications related to CD), all-cause hospitalisation, and all-cause surgery were evaluated from the beginning of maintenance to wk, 52 and compared between patients who achieved endoscopic outcomes at end of induction (wk, 12) and those who did not. Endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) were defined using the Simple Endoscopic Score for CD (SES-CD) (Figure, 1–3), as scored by a blinded central reviewer.

Results

A total of, 298 patients were included in the analyses. Patients who achieved endoscopic response (n=121) at wk, 12 had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52 compared to those who did not achieve an endoscopic response (n=177) at wk, 12 (Figure, 1). Additionally, patients who achieved endoscopic remission at wk, 12 (n=83) had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52, compared to those not achieving endoscopic remission at wk, 12 (n=215) (Figure, 2). Though not statistically significant, numerically lower rates of all-cause surgery were observed for patients who achieved endoscopic remission or endoscopic response at wk, 12. Significantly lower rates of CD-related hospitalisation, CD-related surgery, all-cause hospitalisation, and all-cause surgery by wk, 52 were observed among patients who achieved ulcer-free endoscopy (absence of ulceration) (n=70) vs those who did not (n=228) at wk, 12 (Figure 3).

Conclusion

Early improvement of endoscopic outcomes at wk, 12 is associated with significant reductions in hospitalisations and surgeries through, 52 wks for patients receiving RZB therapy.
P430 Longer-term tofacitinib effectiveness for the treatment of ulcerative colitis: Two-year outcomes from a UK observational cohort study
Authors: Honap S , Sharma E , Ray S , Mawdsley J , Anderson S , Samaan M , Pavlidis P , Irving P
Published: January 2022

Background

Tofacitinib is an oral small molecule inhibitor licensed for the treatment of ulcerative colitis (UC). Whilst real world data has been presented, outcomes beyond, 26 weeks are limited. The objective of this study was to assess the persistence and long-term effectiveness of tofacitinib.

Methods

We conducted a retrospective observational cohort study, using a prospectively maintained database, at a large UK IBD tertiary referral centre. The primary objective was to assess the proportion of patients in deep remission at one year. Deep remission was defined as corticosteroid free clinical remission (CSFR) and endoscopic remission (Mayo Endoscopic Subscore (MES) of, 0 or, 1). All adult patients receiving tofacitinib for moderate to severe UC were included from October, 2018 to October, 2021. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI); clinical response and remission were defined as a reduction of SCCAI ≥3 and a SCCAI ≤2, respectively. All analyses were based on an intention-to-treat principle, and we used non-responder imputation in cases of missingness.

Results

In total, 103 patients were included with a median follow up duration of, 53 weeks (range, 1–156). Prior to treatment, patients had active disease clinically (median SCCAI, 7 (range, 0–15) and endoscopically (median MES, 3) with, 54% on corticosteroids. The cohort had refractory disease;, 90% were anti-TNF-experienced and, 48% had prior exposure to at least two different biologic classes. Table, 1 shows the baseline characteristics of the cohort and figure 1 shows patient disposition in the study. Median treatment duration on, 10mg bd was, 18 weeks (range, 1–135);, 27% (n=15) were on, 10mg BD at one year and, 11% (n=3) at two years. At, 52 weeks, 61% were in CSFR, 38% in endoscopic remission, and, 36% in deep remission (figure 2). Deep remission was not associated with baseline variables, including prior biologic exposure or disease severity on univariate analyses. Faecal calprotectin fell from median, 451ug/g [range, 5-6020] at baseline to, 86ug/g [range, 5-2360] at week, 52 (n=41, p<0.001), but CRP change was not significant. Three-quarters of those remaining on tofacitinib at, 104 weeks (n=27) were in deep remission. The Kaplan Meier estimated probability of remaining on tofacitinib was, 62% (95% CI, 51–71%) at week, 52 and, 44% (CI, 95%, 32–54%) at week, 104 (figure 3).

Conclusion

Longer term effectiveness and treatment persistence data in a cohort of highly refractory UC patients is reassuring.
P559 Cannabis Improves Sleep Quality in Patients with Inflammatory Bowel Diseases in a Prospective Observational Study
Authors: Hirsch A , Seidenberg C , Fliss Isakov N , Meiri D , Maharshak N
Published: January 2022

Background

Poor sleep is associated with adverse health consequences and was shown to be associated with subclinically active inflammatory bowel diseases (IBD).

Altered sleep patterns in IBD patients were associated with frequent disease flares and lower quality of life.

The aim of this study was to assess the effect of cannabis use on sleep quality in IBD patients.

Methods

We conducted a prospective observational cohort study enrolling 160 IBD patients who were prescribed medical cannabis.

Patients who changed medication during the trial, reported use of cannabis 3 months before the trial, or failed to follow up were excluded from the analysis.

Patients filled questionnaires at baseline and after 3 and 6 months of therapy. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI).

Results

A total of 91 patients were included, of these 62.6(57%) were males and 74(81.3%) were diagnosed with Crohn’s disease (CD).

Their median age was 36.71 years (range 20.1–73.2) and their median disease duration was 9 years (range 0.5–55.1).

The median cannabis dose prescribed was 20 grams (range 10–40).

Patients reported an improved sleep quality with decreased mean PSQI score after 3 months (7.1±3.85 vs 7.8±3.9, p=0.004) and further improvement after 6 months (6.9±3.7 vs 7.8±3.9, p=0.006) of cannabis therapy, compared to baseline.

Cannabis therapy was safe with no severe adverse or side effects.

Conclusion

Cannabis use is an effective and safe intervention to improve sleep quality in IBD patients.

The impact of cannabis on the disease activity and its association with sleep improvement in these patients should be further explored.
P563 Association between smoking status and the efficacy and safety of tofacitinib in patients with Ulcerative Colitis: Data from the tofacitinib clinical programme
Authors: Rubin D T , Torres J , Regueiro M , Reinisch W , Prideaux L , Kotze P G , Tan F H , Gardiner S , Mundayat R , Cadatal M J , Ng S C
Published: January 2022

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). Ex-smokers have an increased risk of UC, but the response to therapy in these patients (pts) has not been previously evaluated. We assessed the impact of smoking status on the efficacy and safety of tofacitinib in the UC clinical programme.

Methods

Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in P2 (safety only)/P3/OLE/P3b/4 studies. Efficacy endpoints were summarised by treatment allocation; pt characteristics and AEs were summarised by tofacitinib predominant dose.

Results

This analysis included 1156 pts (ever smokers, n=416 [36.0%; current smokers, n=59 (5.1%); ex-smokers, n=357 (30.9%)]; never smokers, n=740 [64.0%]; Table 1). Compared with never smokers, ever smokers were older and more likely to have a prior history of myocardial infarction, diabetes mellitus, or ischaemic or coronary heart disease. The proportion of pts achieving efficacy endpoints was generally similar across tofacitinib treatment groups regardless of smoking status (Table 2). AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection, specifically 10.8% had herpes zoster (non-serious and serious), 12.0% had a Clostridioides difficile infection and 19.5% had a lower respiratory tract infection; corresponding values for each AE among never smokers were 53.1%, 6.8%, 8.5% and 11.4% (Table 1). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers; thromboembolic events were reported in 1.0% of ever smokers and 0.9% of never smokers. Malignancies (excl. non-melanoma skin cancer [NMSC]) occurred in 2.5% of ever smokers and 1.5% of never smokers; NMSC occurred in 3.7% and 1.0%, respectively. In total, 0.6% of never smokers had colorectal cancer and there were no cases in ever smokers.

Conclusion

The efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. This study is limited by the combined analysis of current and ex-smokers and unknown factors such as the degree of smoking and the time between smoking cessation and UC diagnosis. These data are consistent with previous reports in the general population and pts with UC.1,2

References

1. Meserve J et al. Clin Gastroenterol Hepatol 2019; 7: 1533–1540.

2. Rogers MA et al. PLoS One 2012; 7: e42091.
P608 Systematic review: The impact and importance of body composition in Inflammatory Bowel Disease
Authors: Ding N , Tassone D , Al Bakir I , Wu K , Connell W , Thompson A , Malietzis G , Lung P , Singh S , Choi C H , Gabe S , Jenkins J , Hart A
Published: January 2022

Background

Alterations in body composition are common in Inflammatory Bowel Disease (IBD) and have been associated with differences in patient outcomes. We systematically reviewed the literature to consolidate knowledge on the impact and importance of body composition in IBD.

Methods

We conducted a systematic review according to PRISMA guidelines. A systematic search of MEDLINE, EMBASE and conference proceedings was undertaken by combining two key research themes: Inflammatory Bowel Disease and body composition. Studies which examined alterations in body composition in patients with IBD and studies which explored the impact of body composition on IBD therapeutic outcomes and prognosis were included.

Results

55 studies were included in this review. 31 studies focused on the impact of Inflammatory Bowel Disease on body composition with a total of 2,279 patients and mean age of 38.4 years. Of these, 1,071 (47%) were male. 1470 (64.5%) patients had CD and 809 (35.5%) had UC. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. 24 additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition were associated with poorer prognoses including higher rates of surgical intervention, post-operative complications, and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response were seen in patients with myopaenia.

Conclusion

Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impact of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.
P653 The changing epidemiology of IBD in the western world: a population-based study from Denmark
Authors: Agrawal M , Christensen H , Bøgsted M , Colombel J F , Jess T , Allin K
Published: January 2022

Background

Mitigating the burden of inflammatory bowel disease (IBD) in Western countries requires understanding how its epidemiology is evolving. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2018 in the Danish nationwide cohort.

Methods

We used the Danish Civil Registration System (CRS) to obtain demographic information on all residents in Denmark between January 1, 1995 and December 31, 2018. We obtained information on Crohn’s disease (CD) and ulcerative colitis (UC) diagnosis from the National Patient Registry (NPR) using International Classification of Disease 8/10 codes. IBD diagnosis was defined as having at least two CD- or UC-related registrations within a two-year period and the date of the first IBD-related registration was considered as the date of diagnosis. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex.

Results

52,407 individuals met the criteria for IBD diagnosis in the period 1995–2018, of which 17,355 (33%) were diagnosed with CD and 35,052 (67%) were diagnosed with UC. The median age at diagnosis (IQR) for CD and UC was 34 (22, 53) and 43 (29, 60) years, respectively. 9,745 (56.2%) and 18,332 (52.3%) individuals with CD and UC, respectively, were of female sex. During the study period, 1995–2018, the overall incidence rate (95% CI) rose from 9.2 (8.4, 10) per 100,000 person years (PY) to 18 (16.8, 19) per 100,000 PY for CD, corresponding to a 94.9% increase, and from 21.1 (19.9, 22.4) per 100,000 PY to 28.4 (27, 29.8) per 100,000 PY for UC, corresponding to a 34.1% increase. The incidence rates of CD and UC increased for all age groups, at different rates, highest for CD in age group 15–39 years (Figure). While CD incidence was consistently higher in women, increase in CD and UC incidence was comparable between both sexes. The prevalence of IBD also increased from 1995–2018 (225.6% and 218.4% for CD and UC, respectively) with the greatest increase in UC prevalence among individuals older than 40 years of age (248.4%).

Conclusion

The epidemiology of IBD has shifted in the last 20 years with a still increasing incidence of CD and UC in young adults, and a sharply increased prevalence in older age groups, especially for UC. These findings have implications towards understanding environmental shifts associated with this evolution as well as preparing for management of an aging IBD population.
P682 Predictors of response to biologics in Ulcerative Colitis: A population-based study from the epi-IIRN
Authors: Atia O , Lujan R , Greenfeld S , Kariv R , Matz E , Dotan I , Nevo D , Turner D
Published: January 2022

Background

Identifying prognostic factors of therapeutic failure, may facilitate balancing the risks and benefits of biologic treatment. In this population-based study, we aimed to explore predictors of therapeutic failure of biologics in Ulcerative Colitis (UC).

Methods

We retrieved data from two of four Health Maintenance Organizations in Israel, covering 38% of the population and part of the validated epi-IIRN IBD cohort. We included an inception cohort of UC patients, diagnosed since 2005, who were commenced on biologics. Those who underwent colectomy within 90 days from diagnosis were excluded. The primary outcome was therapeutic failure (i.e. discontinuation of treatment or need for colectomy or >1 short steroid courses). The secondary outcome was primary non-response (PNR; i.e. therapeutic failure within 4 months of initiation). Predictors were sought through Cox proportional hazard model.

Results

A total of 910 patients were included (246 [27%] pediatric-onset, 664 [73%] adults) with a median follow-up of 7.9 years (IQR 4.9–12.0). The probability of PNR was 16% and of therapeutic failure 35%, 55% and 63% after one, three and five years after commencing biologics, respectively. Older age at diagnosis (HR 1.01 [95%CI 1.005–1.01]), number of flares prior to initiation of biologics (HR 1.1 [95%CI 1.05–1.2]) and steroid use prior to biologics (HR 1.3 [95%CI 1.1–1.6]) were associated with therapeutic failure. PNR was associated with use of steroids prior to initiation of biologics (HR 2.1 [95%CI 1.4–3.3]). Laboratory blood work, including CRP, ESR, albumin, leukocytes, hemoglobin and platelets did not predict therapeutic failure, whether at diagnosis (HR 1.1 [95%CI 0.6–2.0]) or at initiation of biologics (HR 1.2 [95%CI 0.7–2.1]).

Conclusion

One third of UC patients failed to response to biologic treatment within one year. Older age at diagnosis and disease severity prior to biologic treatment, reflected by number of flares and steroid use, predicted therapeutic failure.
P709 Distinct Pattern of Gut Microbial Dysbiosis in Crohn’s Disease and Intestinal Tuberculosis - A Machine Learning-based classification model
Authors: Markandey M , Bajaj A , Vuyyuru S K , Mohta S , Singh M , Verma M , Kumar S , Kante B , Kumar P , Makharia G , Kedia S , Ahuja V
Published: January 2022

Background

Crohn’s disease (CD) and intestinal tuberculosis (ITB) are chronic granulomatous inflammatory disorders characterized by a compromised mucosal immunity. Even with diverging etiologies, CD and ITB presents an uncanny resemblance in clinical manifestation resulting in diagnostic dilemma. The gut microbiota regulates myriad of gut mucosal immunological processes. Present study aims to decipher gut microbial dysbiosis in the two disorders and utilize the CD and ITB-specific gut dysbiosis to construct a machine learning (ML)-based predictive model, which can aid in their differential diagnosis.

Methods

Fecal samples from healthy controls (n=12) and from patients with CD (n=23) and ITB (n=25) were subjected to 16S (V3-V4) amplicon sequencing. Processing of raw reads, construction of ASV feature tables, diversity, core microbiome analysis and ML classifier construction was done using QIIME2-2021.4. Differential abundance analysis (DAA) between the groups was carried out using Deseq2, after adjusting for the subject-specific confounders.

Results

The α and β diversity indices in CD and ITB groups were significantly reduced than HC group (p = 0.011 and 0.012 resp.), with no significant differences between the two diseases (Fig.1A, 1B). On comparison with HC, CD and ITB groups showed reduction in members of Firmicutes and Bacteroidetes, with enhancement of Actinobacteria and Proteobacteria (Fig.1C and 1D). DAA (FDR q <0.1, FC >2.5) between CD and ITB groups revealed expansion of Succinivibrio dextrinisolvens, Odoribacter splanchnicus, Megasphaera massiliensis, Bacteroides uniformis and B.xylanisolvens in CD group, while Clostridium sp., Haemophilus parainfluenzae and Bifidobacterium sp. were elevated in ITB (Fig.2A). Random Forest-based ML model constructed on the basis of raw microbiome reads and using 80% of the samples to train the model, showed predictive accuracy of 0.78 (AUC=93%). (Fig.2B)

Conclusion

Our study shows that CD and ITB witnesses significant changes in gut microbial structure. With no significant differences in microbial diversity between two diseases, the signature of gut dysbiosis is distinct between CD and ITB. Exploitation of these differences to construct ML models can potentiate differential diagnosis of CD and ITB.
COVID-19 as a trigger for innovation in policy action for older persons? Evidence from Asia
Authors: Gietel-Basten Stuart , Matus Kira , Mori Rintaro
Published: January 2022

COVID-19 has had a disproportionate impact on older people, in terms of their susceptibility to the disease and increased fatality rates, while also by creating barriers to health care access, social isolation, psychological and financial burdens. Policy responses provide an opportunity to understand whether the demands of this crisis have led to the development of policy innovations to meet the needs of aging populations. We analyzed an illustrative corpus of policies collected by HelpAge International across Asia in Afghanistan, Bangladesh, India, Iran, Japan, Korea, Myanmar, Pakistan, and Vietnam. We identified different policy types that impacted older persons during the pandemic. We also observed the degree to which these policies support arguments for paradigmatic policy changes by examining different models of intersectoral and multisectoral collaborations, and the kinds of policies where these multiactor arrangements were the most common. From our analysis, we identify two main areas where COVID-19 policies are most likely to lead to more long-lasting innovation in Asia. The first is in the upgrading of infrastructures to ensure access to benefits, and to develop remote and doorstep banking. The second area is well-being and caring support, such as the development of programs to provide increased services to support home-based older persons, including telemedicine, delivery services for medical and other supplies, and remote support for older persons and their carers. These changes, while important, are consistent with “acceleration” models of policy change, where COVID-19 responses sped up, and scaled up, programs consistent with current institutional and organizational structures.
The return of Keynesianism? Exploring path dependency and ideational change in post-covid fiscal policy
Authors: Chohan Usman W
Published: January 2022

The aim of this article is to explore the nature of policy change in the domain of public finance (fiscal policy) in the wake of the coronavirus disease (Covid-19) pandemic as well as for a post-Covid era. It draws upon the literatures of path dependency and ideational change in public policy to consider three broad questions: (1) whether the pandemic really is a critical juncture for policy change; (2) whether the extant neoliberal austerity paradigm has faced lasting ideational displacement by Keynesianism; and (3) whether Covid-19 has really punctuated the existing fiscal policy equilibrium or rather served as a path-clearing accelerator of public finance trends that were already underway. The article then suggests three potential future trajectories: Keynesian, neoliberal, and mixed/other to consider how the path of policy change might materialize in the fiscal realm in the post-Covid era.
Effect of Varying Repositioning Frequency on Pressure Injury Prevention in Nursing Home Residents: TEAM-UP Trial Results
Authors: Yap Tracey L. , Horn Susan D. , Sharkey Phoebe D. , Zheng Tianyu , Bergstrom Nancy , Colon-Emeric Cathleen , Sabol Valerie K. , Alderden Jenny , Yap Winston , Kennerly Susan M.
Published: January 2022

OBJECTIVE

To investigate the clinical effectiveness of three nursing-home-wide repositioning intervals (2-, 3-, or 4-hour) without compromising pressure injury (PrI) incidence in 4 weeks.

METHODS

An embedded pragmatic cluster randomized controlled trial was conducted in nine nursing homes (NHs) that were randomly assigned to one of three repositioning intervals. Baseline (12 months) and 4-week intervention data were provided during the TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study. Intervention residents were without current PrIs, had PrI risk (Braden Scale score) ≥10 (not severe risk), and used viable 7-inch high-density foam mattresses. Each arm includes three NHs with an assigned single repositioning interval (2-, 3-, or 4-hour) as standard care during the intervention. A wireless patient monitoring system, using wearable single-use patient sensors, cued nursing staff by displaying resident repositioning needs on conveniently placed monitors. The primary outcome was PrI incidence; the secondary outcome was staff repositioning compliance fidelity.

RESULTS

From May 2017 to October 2019, 1,100 residents from nine NHs were fitted with sensors; 108 of these were ineligible for some analyses because of missing baseline data. The effective sample size included 992 residents (mean age, 78 ± 13 years; 63% women). The PrI incidence during the intervention was 0.0% compared with 5.24% at baseline, even though intervention resident clinical risk scores were significantly higher (P < .001). Repositioning compliance for the 4-hour repositioning interval (95%) was significantly better than for the 2-hour (80%) or 3-hour (90%) intervals (P < .001).

CONCLUSIONS

Findings suggest that current 2-hour protocols can be relaxed for many NH residents without compromising PrI prevention. A causal link was not established between repositioning interval treatments and PrI outcome; however, no new PrIs developed. Compliance improved as repositioning interval lengthened.
Nonoperative Treatment of Posterior Wall Acetabular Fractures After Dynamic Stress Examination Under Anesthesia: Revisited
Authors: McNamara Andrew R. , Boudreau John A. , Moed Berton R.
Published: January 2022

Objectives:

Performing an examination under general anesthesia (EUA) using dynamic stress fluoroscopy of patients with posterior wall acetabular fractures has been used as a tool to determine hip stability and the need for surgical intervention. The purpose of this study was to further evaluate the effectiveness of this technique, from a source other than its primary advocates, in patients with posterior wall acetabular fractures less than or equal to 50% who were stable on EUA and treated nonoperatively.

Design:

Retrospective case series.

Setting:

University Level 1 Trauma Center.

Participants:

Seventeen patients with a posterior wall acetabular fracture stable on EUA treated nonoperatively.

Intervention:

The patients were treated nonoperatively as guided by an EUA negative for instability. Patient follow-up averaged 30 months (range, 6–64 months).

Main Outcome Measurements:

Outcome evaluation included the modified Merle d'Aubigné clinical score and the Short Musculoskeletal Function Assessment Questionnaire. Radiographic evaluation for subluxation or arthritis consisted of the 3 standard pelvic radiographs.

Results:

Radiographic evaluation showed all hips to be congruent with a normal joint space. Sixteen of the 17 patients had radiographic outcomes rated as “excellent”; 1 patient was rated “good.” The modified Merle d'Aubigné score (obtained in 12 patients) averaged very good, with only 1 having less than a good (graded as fair) clinical outcome. The Short Musculoskeletal Function Assessment Questionnaire scores (from 11 patients) were not significantly different from normal and were within the normal reported values for all indices and categories. There was no correlation between fracture fragment size and outcome.

Conclusions:

This study further supports the contention that a stable hip joint, as determined by EUA, after posterior wall acetabular fracture treated nonoperatively is predictive of continued joint congruity, an excellent radiographic outcome, and good-to-excellent early clinical and functional outcomes.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Identification and Assessment of Strategies to Address Gender Inequity in the Specialty of Critical Care Medicine: A Scoping Review, Modified Consensus Process, and Stakeholder Meeting
Authors: Parsons Leigh Jeanna , de Grood Chloe , Brundin-Mather Rebecca , Dodds Alexandra , FitzGerald Emily A. , Kemp Laryssa , Mizen Sara J. , Whalen-Browne Liam , Stelfox Henry T. , Fiest Kirsten M. ,   on behalf of the Canadian Critical Care Gender Equity Forum Panel
Published: January 2022

OBJECTIVES:

We sought to identify and prioritize improvement strategies that Critical Care Medicine (CCM) programs could use to inform and advance gender equity among physicians in CCM.

DESIGN:

This study involved three sequential phases: 1) scoping review that identified strategies to improve gender equity in all medical specialties; 2) modified consensus process with 48 CCM stakeholders to rate and rank identified strategies; and 3) in-person stakeholder meeting to refine strategies and discuss facilitators and barriers to their implementation.

SETTING:

CCM.

SUBJECTS:

CCM stakeholders (physicians, researchers, and decision-makers; mutually inclusive).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We identified 190 unique strategies from 416 articles. Strategies were grouped thematically into 20 categories across four overarching pillars of equity: access, participation, reimbursement, and culture. Participants prioritized 22 improvement strategies for implementation in CCM. The top-rated strategy from each pillar included: 1) nominate gender diverse candidates for faculty positions and prestigious opportunities (equitable access); 2) mandate training in unconscious bias and equitable treatment for committee (e.g., hiring, promotion) members (equitable participation); 3) ensure equitable starting salaries regardless of sex or gender (equitable reimbursement); and, 4) conduct 360° evaluations of leaders (including their direct work circle of supervisors, peers, and subordinates) through a diversity lens (equitable culture). Interprofessional collaboration, leadership, and local champions were identified as key enablers for implementation.

CONCLUSIONS:

We identified stakeholder-prioritized strategies that can be used to inform and enhance gender equity among physicians in CCM under four overarching equity pillars: access, participation, reimbursement, and culture. Implementation approaches should include education, policy creation, and measurement, and reporting.
Serial Thromboelastography and the Development of Venous Thromboembolism in Critically Ill Patients With COVID-19
Authors: Marvi Tanya K. , Stubblefield William B. , Tillman Benjamin F. , Tenforde Mark W. , Patel Manish M. , Lindsell Christopher J. , Self Wesley H. , Grijalva Carlos G. , Rice Todd W. ,   for the Influenza and Other Viruses in the Acutely Ill (IVY) Network
Published: January 2022

OBJECTIVES:

To test the hypothesis that relatively lower clot strength on thromboelastography maximum amplitude (MA) is associated with development of venous thromboembolism (VTE) in critically ill patients with COVID-19.

DESIGN:

Prospective, observational cohort study.

SETTING:

Tertiary care, academic medical center in Nashville, TN.

PATIENTS:

Patients with acute respiratory failure from COVID-19 pneumonia admitted to the adult medical ICU without known VTE at enrollment.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Ninety-eight consecutive critically ill adults with laboratory-confirmed COVID-19 were enrolled. Thromboelastography parameters and conventional coagulation parameters were measured on days 0 (within 48 hr of ICU admission), 3, 5, and 7 after enrollment. The primary outcome was diagnosis of VTE with confirmed deep venous thrombosis and/or pulmonary embolism by clinical imaging or autopsy. Twenty-six patients developed a VTE. Multivariable regression controlling for antiplatelet exposure and anticoagulation dose with death as a competing risk found that lower MA was associated with increased risk of VTE. Each 1 mm increase in enrollment and peak MA was associated with an 8% and 14% decrease in the risk of VTE, respectively (enrollment MA: subdistribution hazard ratio [SHR], 0.92; 95% CI, 0.87–0.97; p = 0.003 and peak MA: SHR, 0.86; 95% CI, 0.81–0.91; p < 0.001). Lower enrollment platelet counts and fibrinogen levels were also associated with increased risk of VTE (p = 0.002 and p = 0.01, respectively). Platelet count and fibrinogen level were positively associated with MA (multivariable model: adjusted R
2 = 0.51; p < 0.001).

CONCLUSIONS:

When controlling for the competing risk of death, lower enrollment and peak MA were associated with increased risk of VTE. Lower platelet counts and fibrinogen levels at enrollment were associated with increased risk of VTE. The association of diminished MA, platelet counts, and fibrinogen with VTE may suggest a relative consumptive coagulopathy in critically ill patients with COVID-19.
Contribution of Coagulopathy on the Risk of Bleeding After Central Venous Catheter Placement in Critically Ill Thrombocytopenic Patients
Authors: van Baarle Floor L.F. , Tisheh Arezoe , Jhingoeriesingh Shanisa S. , Vlaar Alexander P. J. , Biemond Bart J.
Published: January 2022

Objectives:

Critically ill patients often undergo central venous catheter placement during thrombocytopenia and/or coagulopathy. It is unclear whether severe coagulopathy increases the risk of postprocedural bleeding in critically ill patients with severe thrombocytopenia.

Design:

Single-center retrospective cohort study.

Setting:

Academic mixed ICU in Amsterdam, the Netherlands.

Patients:

Consecutive severely thrombocytopenic (platelet count ≤ 50 × 109/L) patients who underwent central venous catheter placement between February 2016 and February 2020.

Interventions:

Central venous catheter placement in patients with both severe thrombocytopenia and severe coagulopathy (international normalized ratio > 1.5 and/or activated partial thromboplastin time > 45 s) versus patients with severe thrombocytopenia and normal or mildly prolonged international normalized ratio and activated partial thromboplastin time.

Measurements and Main Results:

We included 289 central venous catheter placements in 175 patients, 112 in patients with and 172 in patients without severe coagulopathy. Median (interquartile range) platelet count was 27 (16–38) and equal for both groups. There were 44 bleeding episodes at the central venous catheter insertion site (15.5%), of which four (1.4%) were grade 2 and two (0.7%) were grade 3. There were 19 bleeding episodes (17.0%) versus 25 bleeding episodes (14.5%) in the coagulopathy and noncoagulopathy groups, of which one and five were of grade 2 or higher, respectively. After correction for confounders, coagulopathy had no effect on bleeding: odds ratio (95% CI) 0.96 (0.24–3.88). Before central venous catheter placement, 116 (40.8%) patients received platelet transfusion. Bleeding at the central venous catheter insertion site occurred in 19 of 116 patients (16.4%) and 25 of 168 patients (14.9%) who did and did not receive platelet transfusion. After correction for confounders, platelet transfusion had no effect on bleeding: odds ratio (95% CI) 0.73 (0.18–2.83).

Conclusions:

Coagulopathy was not associated with an increased bleeding risk in severely thrombocytopenic ICU patients undergoing ultrasound guided central venous catheter placement. Prophylactic platelet transfusion in patients with severe thrombocytopenia was not associated with a reduced risk of bleeding.
Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU
Authors: Quan Michele , Cho Nam , Bushell Thomas , Mak Joseph , Nguyen Nolan , Litwak Jane , Rockwood Nicholas , Nguyen H. Bryant
Published: January 2022

IMPORTANCE:

Angiotensin II (ATII) was approved for septic or other distributive shock due to its property of increasing blood pressure within 3 hours. Limited data exist regarding its effectiveness when used in real-world clinical practice.

OBJECTIVES:

This study examined ATII as a third-line vasopressor based on institutional approval.

DESIGN:

Retrospective observational cohort study.

SETTING AND PARTICIPANTS:

Medical ICU at an academic tertiary care medical center. Adult patients requiring 3 or more vasopressor agents for septic shock or other forms of distributed shock from September 1, 2018, to January 31, 2020.

MAIN OUTCOMES AND MEASURES:

Effect of ATII after norepinephrine and vasopressin on mortality and mean arterial blood pressure response after 3 hours of administration.

RESULTS:

One-hundred forty-seven patients, 56 receiving ATII and 91 receiving another vasopressor (non-ATII), were enrolled. Patients in the ATII group had higher mortality compared to the non-ATII group, and more required 5 or greater vasopressor agents (p < 0.01). After propensity score weighting, there remains a trend in higher mortality in the ATII compared to non-ATII group, but not statistically significant (86.0% vs 71.0%, p = 0.16). More patients in the ATII group continued to require 5 or greater vasopressor agents compared to the non-ATII group after propensity score weighting (45.9% vs 12.5%, p < 0.01). SOFA score was the only variable associated with mortality (OR = 1.25, 95% CI, 1.05–1.49; p = 0.01). Patients were considered a “responder” if mean arterial pressure greater than 65 mm Hg at 3 hours after the third vasopressor was initiated. Among the ATII group, 37.5% patients were responders compared to 45.1% responders in the non-ATII group (relative risk = 1.07, 95% CI, 0.6–1.93; p = 0.81).

CONCLUSIONS AND RELEVANCE:

Although previous data support the use of ATII due to its favorable hemodynamic response in patients with distributive shock, there was no observed benefit in mortality or hemodynamic response with ATII as a third-line vasopressor in our study of real-world patients.
Adapting digital health interventions for the evolving HIV landscape: examples to support prevention and treatment research
Authors: Budhwani Henna , Kiszla B. Matthew , Hightow-Weidman Lisa B.
Published: January 2022

Purpose of review

Although many HIV prevention and/or treatment digital health interventions (DHIs) have shown feasibility and acceptability, fewer have indicated efficacy, and only a subset have been adapted for new contexts. Adaptation is a key element of pragmatic implementation science research. Adaptation is cost effective and time efficient compared with new development. Leveraging adaptation can lead to accelerated scale-up and enhanced public health impact. Considering the value of adaptation, the purpose of this piece is to present examples of DHI to DHI adaptation sequences to inform future HIV prevention and/or treatment research.

Recent findings

From an examination of recent academic articles (01 November 2016 to 31 October 2021), we identified adaptation sequences that included an original DHI with at least two adaptations. Four models are presented herein; examples consist of adapted DHIs for new population, health outcome, geography, or a combination thereof.

Adaptation is a promising scientific approach to expeditiously respond to the evolving HIV landscape. We present examples of DHI adaptations alongside considerations for each type of adaptation; we also present adaptation challenges with responsive strategies. We suggest when conducted with attention to rigor (leveraging adaptation frameworks, community engagement, and tailoring content), adaptation is a powerful tool to pragmatically address the HIV epidemic.
Psychological Distress of Healthcare Workers in Québec (Canada) During the Second and the Third Pandemic Waves
Authors: Carazo Sara , Pelletier Mariève , Talbot Denis , Jauvin Nathalie , De Serres Gaston , Vézina Michel
Published: January 2022

Objective

We aimed to measure the prevalence of psychological distress among Quebec healthcare workers (HCWs) during the second and third pandemic waves and to assess the effect of psychosocial risk factors (PSRs) on work-related psychological distress among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected (cases) and non-infected (controls) HCWs.

Methods

A self-administered survey was used to measure validated indicators of psychological distress (K6 scale) and PSR (questions based on Karasek and Siegrist models, value conflicts, and work-life balance). Adjusted robust Poisson models were used to estimate prevalence ratios.

Results

Four thousand sixty eight cases and 4152 controls completed the survey. Prevalence of high work-related psychological distress was 42%; it was associated with PSRs (mainly work-life balance, value conflicts, and high psychological demands) but not with SARS-CoV-2 infection.

Conclusion

Primary prevention measures targeting PSRs are needed to reduce mental health risks of HCWs.
Vestibular and Balance Impairment Is Common in Children With Primary Ciliary Dyskinesia
Authors: Zawawi Faisal , Papsin Blake C. , Dell Sharon , Cushing Sharon L.
Published: January 2022

Objective:

Primary ciliary dyskinesia (PCD) is a rare genetic disorder that presents with a wide range of respiratory complaints. The most common otologic associated disorder is middle ear effusion. We ask if children with PCD suffer from vestibular impairment.

Study Design:

Cross-sectional cohort study.

Setting:

Tertiary pediatric referral hospital.

Patients/Participants:

Children with confirmed PCD.

Intervention/Methods:

All included participants were clinically assessed to be at baseline then basic demographics and medical histories were collected, including the specific genetic mutation these patients have. After which, all patients underwent two vestibular tests. The first was to assess their ability to stand on one foot with their eyes open and then with their eyes closed and the second was video head impulse test (vHIT).

Main Outcome Measures:

Ability standing on one foot with the eyes closed and vHIT.

Results:

During this period, 25 children with PCD were recruited for the study. The mean age at recruitment was 11.26 years (4–18 yr). There were 11 women and 14 men. All patients were able to participate in both tests. Nineteen participants (76%) had vestibular impairment. Fifteen of them failed to stand on one foot with their eyes closed and six of 25 had abnormal vHIT. The most common involved gene was DNAH5 8/25 (32%) and it was associated with vestibular impairment in seven of eight participants (87.5%).

Conclusion:

The majority of children with PCD that we tested suffered from vestibular impairment that was previously undiagnosed. This potentially indicates that imbalance and vestibular pathology is under-diagnosed in children with PCD.