Quality of life instruments in studies of menorrhagia: a systematic review

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Investigation of potential intervention targets to improve insulin action: a therapeutic approach

Impaired insulin action (insulin resistance) is a key factor in the pathogenesis of diabetes mellitus. To investigate therapeutic targets against insulin resistance, this thesis explores the mechanism of action of pharmacological agents and exogenous peptides known or suspected to modify insulin action. These included leptin, a hormone primarily involved in the regulation of body weight; sibutramine, an antiobesity agent; plant-derived compounds (pinitol and chamaemeloside) and agents known to affect insulin sensitivity, e.g. metformin, tolbutamide, thiazolidinediones, vanadyl sulphate and thioctic acid. Models used for investigation included the L6 skeletal muscle cell line and isolated skeletal muscles. In vivo studies were undertaken to investigate glycaemia, insulinaemia, satiety and body weight in streptozotocin-induced diabetic mice and obese (ob/ob) mice. Leptin acutely altered insulin action in skeletal muscle cells via the short form of the leptin receptor. This direct action of leptin was mediated via a pathway involving PI 3-kinase but not Jak2. The active metabolites of sibutramine had antidiabetic properties in vivo and directly improved insulin sensitivity in vitro. This effect appeared to be conducted via a non-PI 3-kinase-mediated increase in protein synthesis with facilitated glucose transport, and was independent of the serotonin and noradrenaline reuptake inhibition produced by sibutramine. Pinitol (a methyl inositol) had an insulin mimetic effect and was an effective glucose-lowering agent in insulinopenic states, acting directly on skeletal muscle. Conversely chamaemeloside appeared to improve glucose tolerance without directly altering glucose transport. Metformin directly increased basal glucose uptake independently of PI 3-kinase, possibly via an increase in the intrinsic activity of glucose transporters. Neither tolbutamide nor thiazolidinediones directly altered insulin sensitivity in L6 skeletal muscle cells: however vanadyl sulphate and thioctic acid increased glucose transport but appeared to exert toxic effects at therapeutic concentrations. Examination of glucose transport in skeletal muscle in this thesis has identified various components of post-receptor insulin signalling pathways which may be targeted to ameliorate insulin resistance. Type 2 Diabetes Mellitus Obesity L6 Skeletal Muscle Cells Glucose Transport Insulin Signalling 2

Quality of life instruments in studies of menorrhagia: a systematic review

BACKGROUND: The use of quality of life (QoL) instruments in menorrhagia research is increasing but there is concern that not enough emphasis is placed on patient-focus in these measurements, i.e. on issues which are of importance to patients and reflect their experiences and concerns (clinical face validity). The objective was to assess the quality of QoL instruments in studies of menorrhagia. STUDY DESIGN: A systematic review of published research. Papers were identified through MEDLINE (1966-April 2000), EMBASE (1980-April 2000), Science Citation Index (1981-April 2000), Social Science Citation Index (1981-April 2000), CINAHL (1982-1999) and PsychLIT (1966-1999), and by manual searching of bibliographies of known primary and review articles. Studies were selected if they assessed women with menorrhagia for life quality, either developing QoL instruments or applying them as an outcome measure. Selected studies were assessed for quality of their QoL instruments, using a 17 items checklist including 10 items for clinical face validity (issues of relevance to patients' expectations and concerns) and 7 items for measurement properties (such as reliability, responsiveness, etc.). RESULTS: A total of 19 articles, 8 on instrument development and 11 on application, were included in the review. The generic Short Form 36 Health Survey Questionnaire (SF36) was used in 12/19 (63%) studies. Only two studies developed new specific QoL instruments for menorrhagia but they complied with 7/17 (41%) and 10/17 (59%) of the quality criteria. Quality assessment showed that only 7/19 (37%) studies complied with more than half the criteria for face validity whereas 17/19 (90%) studies complied with more than half of the criteria for measurement properties (P = 0.0001). CONCLUSION: Among existing QoL instruments, there is good compliance with the quality criteria for measurement properties but not with those for clinical face validity. There is a need to develop methodologically sound disease specific QoL instruments in menorrhagia focussing both on face validity and measurement properties.

Health related quality of life and perception of stigmatisation in adolescents living with sickle cell disease in Nigeria:a cross sectional study

Background: Sickle cell disease impacts the physical, emotional and psychological aspects of life of the affected persons, often times exposing them to disease associated stigma from the society and alters the health related quality of life (HRQoL). This study compared the HRQoL of adolescents with sickle cell disease with their healthy peers, identified socio-demographic and clinical factors impacting HRQoL, and determined the extent and effects of SCD related stigma on quality of life. Procedure: We conducted a cross-sectional survey among 160 adolescents, 80 with SCD and 80 adolescents without SCD. Socio-demographic and clinical data were collected using a pre-tested questionnaire. HRQoL was investigated using the Short Form (SF-36v2) Health Survey. SCD perceived stigma was measured using an adaptation of a perceived stigma questionnaire. Results: Adolescents with SCD have significantly worse HRQoL than their peers in all of the most important dimensions of HRQoL (physical functioning, physical roles limitation, emotional roles limitation, social functioning, bodily pain, vitality and general health perception) except mental health. Recent hospital admission and SCD related complication further lowered HRQoL scores. Over seventy percent of adolescents with SCD have moderate to high level of perception of stigmatisation. Hospitalisation, SCD complication, SCD stigma were inversely, and significantly associated with HRQoL. Conclusions: Adolescents living with SCD in Nigeria have lower health related quality of life compared to their healthy peers. They also experience stigma that impacts their HRQoL. Complications of SCD and hospital admissions contribute significantly to this impairment. Pediatr Blood Cancer 2015;62:1245-1251.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia:the ECLIPSE trial

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena(®), Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

Impact of severity and type of depression on quality of life in cases identified in the community

BACKGROUND: The impact of different levels of depression severity on quality of life (QoL) is not well studied, particularly regarding ICD-10 criteria. The ICD classification of depressive episodes in three levels of severity is also controversial and the less severe category, mild, has been considered as unnecessary and not clearly distinguishable from non-clinical states. The present work aimed to test the relationship between depression severity according to ICD-10 criteria and several dimensions of functioning as assessed by Medical Outcome Study (MOS) 36-item Short Form general health survey (SF-36) at the population level. METHOD: A sample of 551 participants from the second phase of the Outcome of Depression International Network (ODIN) study (228 controls without depression and 313 persons fulfilling ICD criteria for depressive episode) was selected for a further assessment of several variables, including QoL related to physical and mental health as measured with the SF-36. RESULTS: Statistically significant differences between controls and the depression group were found in both physical and mental markers of health, regardless of the level of depression severity; however, there were very few differences in QoL between levels of depression as defined by ICD-10. Regardless of the presence of depression, disability, widowed status, being a woman and older age were associated with worse QoL in a structural equation analysis with covariates. Likewise, there were no differences according to the type of depression (single-episode versus recurrent). CONCLUSIONS: These results cast doubt on the adequacy of the current ICD classification of depression in three levels of severity.

Flexibility of short-strand RNA in aqueous solution as revealed by molecular dynamics simulation:are A′-RNA and A-RNA distinct conformational structures?

We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.