Midwives' ability during third stage of childbirth to estimate postpartum haemorrhage.

Objective: Correctly assessing the amount of blood loss is crucial in order to adequately treat postpartum haemorrhage (PPH) at an early stage and diminish any related symptoms and/or complications.The aim of our study is to analyse correctness in visually estimated blood loss during labour and to measure the differences between subjectively measured and weighted blood losses (ml). Design: Cross-sectional study. Setting: A Swedish maternity unit with 6000 annual births. Participants: Midwives employed at a big maternity unit at a hospital in northern Stockholm, Sweden. Intervention: Midwives assisting 192 vaginal births were asked to visually estimate the blood loss from the assisted delivery. Coasters and sanitary pads were weighed following the birth. We analysed if there were any differences between subjective measured blood loss (ml) and weighted blood loss. These two methods were also compared to quantify concordance between estimated blood volume and the actual volume. Findings: The number of overestimates of blood loss was 45.3 % ( n = 87 ) with an average of 72.9 ml; the number of underestimates was 49.4 % ( n = 95 ) with an average of 73.8 ml. Exact correct estimations of blood loss were done in 5.2 % of the cases ( n = 10 ).The largest overestimation of a postpartum bleeding was by 520 ml; the largest underestimation was by 745 ml. Conclusion: There was both underestimation and overestimation of blood loss. We found small but significant overestimates in PPH < 300 ml (16 ml). In PPH > 300 ml, there was a small but not significant underestimates (34 ml). Based upon our findings, we conclude that it is reasonable to start weighing blood loss when it exceeds 300 ml.

"An Undesired Life Event": A retrospective interview study of Swedish women's experiences of Caesarean Section in the 1970s and 1980s."

BACKGROUND: Giving birth is a transformative event. Memories of the birth often remain in a woman's mind for the rest of her life. Key aspects of a mother's overall birth experience include concerns about the safety and health of the baby, and the first contact the mother has with her child. To the best of our knowledge, research has not yet been published relating to the ways in which women undergoing caesarean sections in the 1970s and 1980s experienced the birth of their baby and whether or not their mode of delivery has affected their reproductive health and their relationship to their child. OBJECTIVE: To describe women's experience of undergoing a caesarean section in the 1970s and 1980s in Sweden. DESIGN: A qualitative method using semi-structured questions and content analysis. PARTICIPANTS: Twenty-two women were interviewed who underwent caesarean section during the 1970s and 1980s in Sweden. RESULTS: The overarching theme surrounding women's experience of having undergone a caesarean section 30-40 years ago is that it is described as "undesired life event". Four categories were established: vaginal birth as the norm; a total loss of control; acceptance and contact with the child. CONCLUSION: Undergoing a caesarean section during the 1970s and 1980s was considered to be an undesired life events. The interlocuters who participated in this study had little knowledge about operative childbirth and were poorly prepared for a complicated birth and postpartum care. The women did not suffer any long-term physiological harm yet were harmed psychologically until they came to terms with their negative experience and reached acceptance of it.

Development of the neurotrophic keratopathy questionnaire: qualitative research.

BACKGROUND: Neurotrophic keratopathy/keratitis (NK) is a rare disease of the cornea that can lead to anatomical loss of the eye. Little is known about the NK experience from the patients' perspective. The objectives of this study were to examine the symptomatic experience and impacts of NK on patients and assess the overall comprehension, relevance, and content validity of a new questionnaire. METHODS: This was a cross-sectional, qualitative study conducted with NK patients with varying levels of disease severity, recruited from one clinical site. One-on-one interviews using concept elicitation and cognitive interviewing techniques were conducted. RESULTS: Fourteen NK patients participated; 64.3% were female (n = 9), mean age was 65.7 ± 13.3, and 14.3% (n = 2), 21.4% (n = 3), and 64.3% (n = 9) were classified as Mackie stage I, stage II, or stage III, respectively. Participants reported 24 concepts, including: redness (n = 12, 86%), sensitivity to light (n = 11, 79%), general discomfort (n = 9, 64%), dry eye (n = 9, 64%), reduced visual acuity (n = 9, 64%), blurred vision (n = 8, 57%), and eye fatigue (n = 8, 57%). No new concepts were reported after the 13th interview. The most frequently reported impacts included frustration (n = 10, 71%), driving impairment (n = 8, 57%), reading impairment (n = 7, 50%), difficulty watching television (n = 7, 50%), and concern with potentially losing their eyesight due to NK (n = 6, 43%). Participants provided positive feedback on the draft NK Questionnaire (NKQ) and felt that it was comprehensive and relevant to their experience with NK. Additionally, the recall period, instructions, item concepts, and response options were well-understood by participants. Minor revisions were made to the tool for consistency (i.e., the timeframe "in the past 7 days" was added to items 12-14); item 14 was modified to include "how often"; examples were added to item 9. CONCLUSIONS: The results of the concept elicitation portion of the qualitative study support the content validity of the draft NKQ. The clinically significant concepts identified in the literature and raised during concept elicitation are included as items in the questionnaire. Further assessment of the psychometric properties should be conducted in support of this new tool to measure the effect of new treatments on symptoms and impacts associated with NK.

Evaluating minimal important differences and responder definitions for the asthma symptom diary in patients with moderate to severe asthma.

BACKGROUND: The Asthma Symptom Diary was developed to assess severity of symptoms in patients with moderate to severe asthma, and has evidence supporting reliability and validity. Only limited information is available on sensitivity to change and responder definitions for the Asthma Symptom Diary. OBJECTIVES: Main study objectives were to evaluate sensitivity to change and provide responder definitions for clinically meaningful effects for the Asthma Symptom Diary. METHODS: This is a secondary analysis of Phase II clinical trial data in patients with moderate to severe asthma, Asthma Symptom Diary (ASD) was collected daily during the 24-week study. The Asthma Control Questionnaire and the Patient Global Assessment were collected at baseline, and week 12 and 24. Analysis of covariance (ANCOVA) models were used to evaluate sensitivity to change in Asthma Symptom Diary scores after 12 and 24 weeks of treatment. Anchor-based methods, using Asthma Control Questionnaire and Patient Global Assessment defined anchors, were used to identify minimal important differences and various responder criteria for changes in mean 7-day ASD score, symptomatic days, and minimal symptom days. RESULTS: Sample was 59% female, 81% White, with a mean age of 47.3 (SD = 13.6) years. ANCOVAs demonstrated significant differences in baseline to week 12 and week 24 changes in mean 7-day Asthma Symptom Diary scores and symptomatic days by Asthma Control Questionnaire (all p < 0.001) and Patient Global Assessment anchors (all p < 0.001). Meaningful responders, from the patient's perspective, were defined as improvements of 0.5-0.6 points (SD = 0.6; scale range 0 to 4) in mean 7-day Asthma Symptom Diary scores, and as a reduction of 2 to 3 Asthma Symptom Diary-based symptomatic days. CONCLUSION: The Asthma Symptom Diary was responsive to changes in clinical status in patients with moderate to severe asthma. Responder definitions were identified, including symptomatic days, for evaluating individual level treatment effects in clinical trials.

Measurement properties of the Short Form-36 (SF-36) and the Functional Assessment of Cancer Therapy - Anemia (FACT-An) in patients with anemia associated with chronic kidney disease.

BACKGROUND: Anemia is a common and debilitating manifestation of chronic kidney disease (CKD). Data from two clinical trials in patients with anemia of CKD were used to assess the measurement properties of the Medical Outcomes Survey Short Form-36 version 2 (hereafter SF-36) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An). The Vitality and Physical functioning domains of the SF-36 and the FACT-An Total, Fatigue and Anemia subscales were identified as domains relevant to CKD-associated anemia. METHODS: A total of 204 patients aged 18-80 years were included in the analyses that included internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficients [ICCs]), convergent and known-groups validity, responsiveness, and estimates of important change. RESULTS: Both the SF-36 and the FACT-An had strong psychometric properties with high internal consistency (Cronbach's alpha: 0.69-0.93 and 0.79-0.95), and test-retest reliability (ICCs: 0.64-0.83 and 0.72-0.88). Convergent validity, measured by correlation coefficients between similar concepts in SF-36 and FACT-An, ranged from 0.52 to 0.77. Correlations with hemoglobin (Hb) levels were modest at baseline; by Week 9, the correlations with Hb were somewhat higher, r = 0.23 (p < 0.05) for SF-36 Vitality, r = 0.22 (p < 0.05) for FACT-An Total, r = 0.26 (p < 0.001) for FACT-Fatigue and r = 0.22 (p < 0.01) for Anemia. Correlations with Hb at Week 13/17 were r = 0.28 (p < 0.001) for SF-36 Vitality and r = 0.25 (p < 0.05) for Role Physical; FACT-An Total correlation was r = 0.33 (p < 0.0001), Anemia was r = 0.28 (p < 0.001), and Fatigue was r = 0.30 (p < 0.001). The SF-36 domains and Component Summary scores (p < 0.05-p < 0.0001) demonstrated ability to detect change. For the FACT-An, significant differences (p < 0.05-p < 0.0001) were observed between responder and non-responder change scores: important change score estimates ranged from 2 to 4 for Vitality and 2-3 for Physical functioning. Important change scores were also estimated for the FACT-An Total score (6-9), the Anemia (3-5), and Fatigue subscale (2-4). CONCLUSIONS: Both the SF-36 Vitality and Physical function scales and the FACT-An Total, Fatigue and Anemia scales, are reliable and valid measures for assessing health-related quality of life in anemia associated with CKD.

Mode of delivery among Swedish midwives and obstetricians and their attitudes towards caesarean section.

BACKGROUND: A knowledge gap exists around midwives' and obstetricians' mode of delivery in comparison to the general population, and if their personal experience influences their attitudes towards different modes of delivery. OBJECTIVES: The aim of the present study was to investigate midwives' and obstetricians' mode of delivery compared to the population at large. The second aim was to see if their mode of delivery had been influenced by the expanded indications for caesarean section as described in medical literature. Thirdly, the differences between obstetricians' and midwifes' attitudes to caesarean section on maternal request was investigated. MATERIAL AND METHOD: Textbooks from midwifery education and medical schools were reviewed using a structured protocol. A questionnaire for midwives and obstetricians containing questions on mode of delivery, attitudes towards patients' autonomy and performing caesarean sections on maternal request was sent to 380 midwives and 97 obstetricians born in 1935, 1955 or 1975 with an invitation to participate in the study. Two hundred and sixty three midwives and 55 obstetricians provided completed responses. RESULTS: The review of textbooks identified that the number of indications for caesarean section has increased. Indications for caesarean section increased in medical textbooks from seven in the oldest books, from year 1955, to 11 in the textbook from 1993. The focus has shifted in more recently published textbooks to prevention of fatal deliveries. In earlier obstetric care they tend to learn to solve the catastrophe when it had occurred. No significant relationship between midwives' and obstetricians; own mode of delivery and their attitudes towards performing a caesarean section on maternal request (p = 0.191) was found. Thirty percent of the obstetricians reported that they would perform a caesarean section if the pregnant woman requested one. The study found a significant difference between the professions in the statement "the proportion of caesarean section is too high" where midwives to a greater extent agreed with the statement (p = 0.033). There were no significant differences between caesarean section as the mode of delivery for midwives and obstetricians as compared to the general population. Midwives born in 1975 had significantly lower rate of instrumental births compared to the population at large (p < 0.05). CONCLUSIONS: Over the years, the indications for caesarean section have increased. The increase is shown in both the textbooks read during the different time periods as well as among the Swedish midwives and obstetricians born in 1955 and 1975.

Wait a minute? An observational cohort study comparing iron stores in healthy Swedish infants at 4 months of age after 10-, 60- and 180-second umbilical cord clamping.

BACKGROUND AND OBJECTIVE: Umbilical cord blood (UCB) is a valuable stem cell source used for transplantation. Immediate umbilical cord (UC) clamping is widely practised, but delayed UC clamping is increasingly advocated to reduce possible infant anaemia. The aim of this study was to investigate an intermediate UC clamping time point and to evaluate iron status at the age of 4 months in infants who had the UC clamped after 60 s and compare the results with immediate and late UC clamping. DESIGN: Prospective observational study with two historical controls. SETTING: A university hospital in Stockholm, Sweden, and a county hospital in Halland, Sweden. METHODS: Iron status was assessed at 4 months in 200 prospectively recruited term infants whose UC was clamped 60 s after birth. The newborn baby was held below the uterine level for the first 30 s before placing the infant on the mother's abdomen for additional 30 s. The results were compared with data from a previously conducted randomised controlled trial including infants subjected to UC clamping at ≤10 s (n=200) or ≥180 s (n=200) after delivery. RESULTS: After adjustment for age differences at the time of follow-up, serum ferritin concentrations were 77, 103 and 114 µg/L in the 10, 60 and 180 s groups, respectively. The adjusted ferritin concentration was significantly higher in the 60 s group compared with the 10 s group (P=0.002), while the difference between the 60 and 180 s groups was not significant (P=0.29). CONCLUSION: In this study of healthy term infants, 60 s UC clamping with 30 s lowering of the baby below the uterine level resulted in higher serum ferritin concentrations at 4 months compared with 10 s UC clamping. The results suggest that delaying the UC clamping for 60 s reduces the risk for iron deficiency. TRIAL REGISTRATION NUMBER: NCT01245296.

Incorporating development of a patient-reported outcome instrument in a clinical drug development program: examples from a heart failure program.

BACKGROUND: Patient-reported outcome (PRO) measures can be used to support label claims if they adhere to US Food & Drug Administration guidance. The process of developing a new PRO measure is expensive and time-consuming. We report the results of qualitative studies to develop new PRO measures for use in clinical trials of omecamtiv mecarbil (a selective, small molecule activator of cardiac myosin) for patients with heart failure (HF), as well as the lessons learned from the development process. METHODS: Concept elicitation focus groups and individual interviews were conducted with patients with HF to identify concepts for the instrument. Cognitive interviews with HF patients were used to confirm that no essential concepts were missing and to assess patient comprehension of the instrument and items. RESULTS: During concept elicitation, the most frequently reported HF symptoms were shortness of breath, tiredness, fluid retention, fatigue, dizziness/light-headedness, swelling, weight fluctuation, and trouble sleeping. Two measures were developed based on the concepts: the Heart Failure Symptom Diary (HF-SD) and the Heart Failure Impact Scale (HFIS). Findings from cognitive interviews suggested that the items in the HF-SD and HFIS were relevant and well understood by patients. Multiple iterations of concept elicitation and cognitive interviews were needed based on FDA request for a broader patient population in the qualitative study. Lessons learned from the omecamtiv mecarbil PRO/clinical development program are discussed, including challenges of qualitative studies, patient recruitment, expected and actual timelines, cost, and engagement with various stakeholders. CONCLUSION: Development of a new PRO measure to support a label claim requires significant investment and early planning, as demonstrated by the omecamtiv mecarbil program.

Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

BACKGROUND: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials. METHODS: A qualitative interview study was conducted among a sample of symptomatic adults with COPD. Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD). All interview transcript data were coded using ATLAS.ti software for content analysis. RESULTS: Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively. The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement. During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %). A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD. Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand. The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary. CONCLUSIONS: This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing.

Patient-Reported Outcomes in Chronic Heart Failure: Applicability for Regulatory Approval.

OBJECTIVES: The study sought to review the characteristics of existing patient-reported outcome (PRO) instruments used with chronic heart failure (HF) patients and evaluate their potential to support an approved U.S. Food and Drug Administration (FDA) product label claim. BACKGROUND: PROs, including symptoms and their associated functional limitations, contribute substantially to HF patient morbidity. PRO measurements capture the patient perspective and can be systematically assessed with structured questionnaires, however rigorous recommendations have been set by the FDA regarding the acceptability of PRO measures as a basis for product label claims. METHODS: Extensive searches of databases and specialty guidelines identified PRO instruments used in patients with chronic HF. Information on critical properties recommended by the FDA guidance were systematically extracted and used to evaluate the selected PRO instruments. RESULTS: Nineteen PRO instruments used with chronic HF patients were identified. The Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire were the most extensively evaluated and validated in studies of this population. However, judged by criteria listed in the FDA PRO guidance, no existing PRO measure met all of the criteria to support a product label claim in the United States. CONCLUSIONS: Currently available chronic HF PRO measures do not fulfill all the recommendations provided in the FDA PRO guidance and therefore may not support an FDA-approved product label claim. Future investigations are merited to develop a PRO measure for use in patients with chronic HF in accordance with the FDA guidance.

Development of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT®) questionnaire: a new patient-reported outcome instrument for PAH.

BACKGROUND: Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance. METHODS: A cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18-80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments. RESULTS: Focus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social impact, cognition, emotional impact). The recall period is the past 24 h for symptoms, and the past 7 days for impacts. CONCLUSIONS: The PAH-SYMPACT® was shown to capture symptoms and their impacts relevant to PAH patients, demonstrating content saturation, concept validity, and ePRO usability. Final content and psychometric validation of the instrument will be based on the results of an ongoing Phase IIIb clinical trial in PAH patients.

Psychometric Properties of the Asthma Symptom Diary (ASD), a Diary for Use in Clinical Trials of Persistent Asthma.

BACKGROUND: No currently available asthma symptom diary has sufficient validation to be recommended for use as a core asthma outcome measure. OBJECTIVE: The objective of this study was to provide validation data for the 10-item asthma symptom diary (ASD). METHODS: Data were collected in a 4-week prospective, observational study. Subjects completed 3 study visits, completing the ASD twice daily at home for 28 days. Psychometric properties in terms of dimensionality, reliability, validity, and responsiveness were assessed. RESULTS: Data from 276 subjects were analyzed; mean age was 42.9 (standard deviation [SD] = 16.4) years, mean asthma duration was 23.3 (SD = 16.8) years, and 69.6% were female. Confirmatory factor and Rasch analysis supported the ASD as unidimensional and adequately measuring the spectrum of asthma symptom severity. High Cronbach's α (0.94) and intraclass correlation coefficients (0.89-0.95) supported reliability. A high correlation between the 7-day average ASD score and the Asthma Control Questionnaire (ACQ) total score (r = 0.75) and Asthma Quality of Life Questionnaire total scores (r = -0.76), and a moderate correlation with FEV1% predicted (r = -0.30) supported convergent validity. Significant differences (P < .001) between groups classified by ACQ scores supported known-group validity. The 7-day average ASD scores were responsive to change, with significantly higher score changes (P < .001) in responders versus nonresponders. Minimally important differences were calculated and found to be in the range of 0.1-0.3. CONCLUSION: Results of this study indicated that the ASD is a reliable and valid asthma symptom measure for use in adult and adolescent asthma patients to evaluate the effect of treatment on asthma in clinical trials.

Health-related quality of life five years after birth of the first child.

OBJECTIVES: The aim of this study was to describe the overall health-related quality of life (HRQoL) in women five years after the birth of their first child as well as the HRQoL in relation to mode of delivery. METHODS: 545 first-time pregnant women, drawn from a hospital situated in Sweden, consented to be included in a cohort. Five years after the birth of the first child, 372 (68%) women agreed to participate in a follow-up study. HRQoL was measured using the Swedish Health-Related Quality of Life Survey (SWED-QUAL) questionnaire. Socio-demographic background and variables related to pregnancy and childbirth were collected using a self-report questionnaire. RESULTS: Overall, the HRQoL was perceived to be good. Suboptimal scores were obtained for the three variables: Sleeping problems, Emotional well-being - negative affect and Family functioning - sexual functioning. Women having a vaginal birth, an instrumental vaginal birth or women who underwent caesarean section on maternal request were more likely to report better perceived HRQoL than women who had undergone an emergency caesarean section or caesarean section due to medical indication. CONCLUSION: This study demonstrates that the overall HRQoL of the women in the cohort was reported as good. Mode of delivery was associated with differences in HRQoL five years after birth of the first child. Our result suggests that some differences in perceived HRQoL persist in the long term.