Anne-Marie Côté

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model

BACKGROUND Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review

Objective To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women. Design Systematic review. Data sources Medline and Embase, the Cochrane Library, reference lists, and experts. Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator. Results 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria. Conclusion The spot protein:creatinine ratio is a reasonable “rule-out” test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.

The 24-hour urine collection: gold standard or historical practice?

OBJECTIVE The objective of the study was to determine completeness of 24-hour urine collection in pregnancy. STUDY DESIGN This was a retrospective laboratory/chart review of 24-hour urine collections at British Columbia Womens Hospital. Completeness was assessed by 24-hour urinary creatinine excretion (UcreatV): expected according to maternal weight for single collections and between-measurement difference for serial collections. RESULTS For 198 randomly selected pregnant women with a hypertensive disorder (63% preeclampsia), 24-hour urine collections were frequently inaccurate (13-54%) on the basis of UcreatV of 97-220 micromol/kg per day (11.0-25.0 mg/kg per day) or 133-177 micromol/kg per day (15.1-20.1 mg/kg per day) of prepregnancy weight (respectively). Lean body weight resulted in more inaccurate collections (24-68%). The current weight was frequently unavailable (28%) and thus not used. For 161 women (81% proteinuric) with serial 24-hour urine levels, a median [interquartile range] of 11 [5-31] days apart, between-measurement difference in UcreatV was 14.4% [6.0-24.9]; 40 women (24.8%) had values 25% or greater, exceeding analytic and biologic variation. CONCLUSION Twenty-four hour urine collection is frequently inaccurate and not a precise measure of proteinuria or creatinine clearance.

Expectant Management of Severe Preeclampsia Remote from Term: A Structured Systematic Review

Objective: To compare outcomes associated with expectant vs. interventionist care of severe preeclampsia in observational studies. Data Sources: Medline (01/1980–07/2007), bibliographies of retrieved papers, personal files, Cochrane Database of Systematic Reviews. Study Selection: Expectant or interventionist care of preeclampsia at <34 wk. Tabulation, Integration, Results: Data abstraction independently by two reviewers. Median [IQR] of clinical maternal/perinatal outcomes presented. Results: 72 publications, primarily from tertiary care centres in Dutch and developed world sites. Expectant care of severe preeclampsia <34 wk (39 cohorts, 4,650 women), for which 40% of women are eligible, is associated with pregnancy prolongation of 7–14 d, and few serious maternal complications (median <5%), similar to interventionist care (2 studies, 42 women). Complication rates are higher with HELLP <34wk (12 cohorts, 438 women) and severe preeclampsia <28wk (6 cohorts, 305 women), similar to interventionist care (6 cohorts, 467 women and 2 cohorts, 70 women, respectively). Expectant care of HELLP <34 wk (12 cohorts, 438 women) is associated with fewer days gained (median 5), but more serious maternal morbidity (e.g., eclampsia, median 15%). More than half of women have at least temporary improvement of HELLP. In the developed world, expectant (vs. interventionist) care of severe preeclampsia or HELLP <34 wk is associated with reduced neonatal death and complications. Stillbirth is higher in Dutch and developing world sites where viability thresholds are higher. For preeclampsia <24wk (4 cohorts), perinatal mortality is >80%. No predictors of adverse maternal/perinatal outcomes were identified (13 studies). Conclusions: Future research should establish the best maternal/fetal monito regimen and indications for delivery with expectant care. A definitive RCT is needed.

Physiotherapists and Use of Low Back Pain Guidelines: A Qualitative Study of the Barriers and Facilitators

Introduction A new set of clinical practice guidelines (CPGs) for the management of low back pain (LBP) and prevention of persistent disability entitled “Clinic on Low back pain in Interdisciplinary Practice” (CLIP) was developed in the province of Quebec, Canada. The literature shows that simply disseminating CPGs does not necessarily lead to their adoption by clinicians. To improve adherence to CPGs among healthcare professionals, the literature suggests that there is a need to identify and address the factors impeding or facilitating their use. The aim of this study was therefore to identify the barriers to and facilitators of CLIP CPG use, as perceived by physiotherapists (PTs). Methods A descriptive study using a qualitative method was conducted with a sample of 16 PTs from a variety of professional backgrounds. Each participant used the CPGs over a 6-week period with two patients suffering from LBP, and then participated in a semi-structured interview in which he or she was asked to identify the barriers and facilitators experienced. Results The participating PTs identified many barriers and facilitators pertaining to the guidelines themselves, the users and the environment. Four key nodes emerged from these barriers and facilitators during data analysis. It appears that the clinicians’ understanding of the CPGs, the level of compatibility between their practices and the CLIP CPG recommendations, the level of CPG relevance as perceived by the clinicians, and their level of agreement with the CPGs, all affected their use of the guidelines. Conclusions In order to increase CLIP CPG use, the implementation strategy to be developed should take into account the barriers and facilitators that were identified in this study.

The Patient’s Perspective of in-Home Telerehabilitation Physiotherapy Services Following Total Knee Arthroplasty

This study aimed at exploring patients’ perceptions regarding telerehabilitation services received post total knee replacement. In this qualitative embedded single case study, semi-structured interviews were conducted with five patients who had previously received in-home telerehabilitation post total knee arthroplasty. Participants were asked to reflect on their 8-week rehabilitation process and on their experience with the home telerehabilitation program. Interviews were transcribed and a qualitative thematic analysis was conducted. Six overarching themes emerged from the patients’ perceptions: (1) improving access to services with reduced need for transportation; (2) developing a strong therapeutic relationship with therapist while maintaining a sense of personal space; (3) complementing telerehabilitation with in-person visits; (4) providing standardized yet tailored and challenging exercise programs using telerehabilitation; (5) perceived ease-of-use of telerehabilitation equipment; and (6) feeling an ongoing sense of support. Gaining a better understating of the patient’s experience in telerehabilitation will be essential as programs continue to be developed and implemented.

The hypertensive disorders of pregnancy (29.3)

Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.

Guidelines on low back pain disability: interprofessional comparison of use between general practitioners, occupational therapists, and physiotherapists.

Study Design. Individual semistructured qualitative interviews. Objective. To evaluate barriers to use of management recommendations, aimed at preventing low back pain (LBP) disability, with general practitioners (GPs), occupational therapists (OTs), and physiotherapists (PTs) working in Quebec (Canada), and identify areas of convergence and divergence between health professions. Summary of Background Data. Studies have demonstrated inadequacies of practices of clinicians with regard to LBP management and prevention of persistent disability. Barriers to use of evidence by clinicians should be evaluated to understand these inadequacies and develop implementation strategies. Methods. Sixteen PTs, 8 OTs, and 8 GPs were recruited with different levels of experience and practice location (urban or rural). They were asked to follow management recommendations (Clinic on Low-back Pain in Interdisciplinary Practice [CLIP] guidelines), with a minimum of 2 patients. Individual semistructured interviews were used to identify barriers to use of management recommendations aimed at preventing LBP disability. Barriers between health professions were compared. Results. Barriers to use were lesser for OTs and greater for GPs, with divergences among PTs. OTs agreed with the guidelines, found them compatible with their current practice, and thought that using them would prevent persistent disability. GPs and PTs thought that the guidelines did not provide enough information on the pathophysiological management of LBP. GPs thought that it would be difficult to implement the guidelines in everyday practice. All 3 groups thought that management recommendations could conflict with patient expectations. Conclusion. To address identified barriers, a process of care is proposed by fitting tasks to the most compatible providers. The task of GPs could focus on pain management through medication, red flag screening, encouragement to stay active, and reassurance. The tasks of PTs could center on pain management, general exercise, and encouragement to stay active. The tasks of OTs could focus on disability prognosis, yellow flags management, and return to activity parameters. The efficacy of this process of care to prevent persistent LBP disability should be assessed in a trial.

Persistent Insulin Resistance in Podocytes Caused by Epigenetic Changes of SHP-1 in Diabetes.

Poor glycemic control profoundly affects protein expression and the cell signaling action that contributes to glycemic memory and irreversible progression of diabetic nephropathy (DN). We demonstrate that SHP-1 is elevated in podocytes of diabetic mice, causing insulin unresponsiveness and DN. Thus, sustained SHP-1 expression caused by hyperglycemia despite systemic glucose normalization could contribute to the glycemic memory effect in DN. Microalbuminuria, glomerular filtration rate, mesangial cell expansion, and collagen type IV and transforming growth factor-β expression were significantly increased in diabetic Ins2+/C96Y mice compared with nondiabetic Ins2+/+ mice and remained elevated despite glucose normalization with insulin implants. A persistent increase of SHP-1 expression in podocytes despite normalization of systemic glucose levels was associated with sustained inhibition of the insulin signaling pathways. In cultured podocytes, high glucose levels increased mRNA, protein expression, and phosphatase activity of SHP-1, which remained elevated despite glucose concentration returning to normal, causing persistent insulin receptor-β inhibition. Histone posttranslational modification analysis showed that the promoter region of SHP-1 was enriched with H3K4me1 and H3K9/14ac in diabetic glomeruli and podocytes, which remained elevated despite glucose level normalization. Hyperglycemia induces SHP-1 promoter epigenetic modifications, causing its persistent expression and activity and leading to insulin resistance, podocyte dysfunction, and DN.

Monitoring Renal Function in Hypertensive Pregnancy

Objective. In hypertensive pregnancy, to compare 24hr creatinine clearance (CrCl) with formulae-derived renal function (Cockcroft-Gault (CG) or Modified Diet in Renal Disease (MDRD)). Study design. Retrospective review (198 women, 63% preeclampsia) using paired t-test (significant p < 0.008) and intraclass correlation coefficients (acceptable >0.70) to compare 24hr and CG CrCl. The 24hr CrCl was compared with each of the CG and MDRD formulae by Bland-Altman plots. Results. For 24hr CrCl, uncorrected values were similar to corrected using pre-pregnancy weight (p = 0.04); other weights gave consistently different CrCl (p < 0.0001). Limits of agreement were wide when CG and MDRD formulae were compared with 24hr CrCl. Compared with 24hr CrCl, MDRD estimates were consistently lower, and CG CrCl higher (current weight) or lower (pre-pregnancy or lean weight). Conclusion. MDRD and CG formulae should not be used in hypertensive pregnancy. Use of serum creatinine is advocated. If 24hr CrCl is performed, any correction should utilize pre-pregnancy weight. Neither the Cockcroft-Gault nor Modified Diet in Renal Disease formulae for glomerular filtration rate estimation are alternatives to 24hr creatinine clearance in hypertensive pregnancy.