Can Intrapartum Cardiotocography Predict Uterine Rupture among Women with Prior Caesarean Delivery?: A Population Based Case-Control Study

Objective

To compare cardiotocographic abnormalities recorded during labour in women with prior caesarean delivery (CD) and complete uterine rupture with those recorded in controls with prior CD without uterine rupture.

Study Design

Women with complete uterine rupture during labour between 1997 and 2008 were identified in the Danish Medical Birth Registry (n = 181). Cases were validated by review of medical records and 53 cases with prior CD, trial of labour, available cardiotocogram (CTG) and complete uterine rupture were included and compared with 43 controls with prior CD, trial of labour and available CTG. The CTG tracings were assessed by 19 independent experts divided into groups of three different experts for each tracing. The assessors were blinded to group, outcome and clinical data. They analyzed occurrence of defined abnormalities and classified the traces as normal, suspicious, pathological or pre-terminal according to international guidelines (FIGO).

Results

A pathological CTG during the first stage of labour was present in 77% of cases and in 53% of the controls (OR 2.58 [CI: 0.96–6.94] P = 0.066). Fetal tachycardia was more frequent in cases with uterine rupture (OR 2.50 [CI: 1.0–6.26] P = 0.053). Significantly more cases showed more than 10 severe variable decelerations compared with controls (OR 22 [CI: 1.54–314.2] P = 0.022). Uterine tachysystole was not correlated with the presence of uterine rupture.

Conclusion

A pathological cardiotocogram should lead to particular attention on threatening uterine rupture but cannot be considered a strong predictor as it is common in all women with trial of labour after caesarean delivery.     

Statins and Hip Fracture Prevention – A Population Based Cohort Study in Women

Objective

To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women.

Design

A register-based cohort study.

Setting

Finland.

Participants

Women aged 45–75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥80% during the subsequent five years (n = 40 254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585).

Main Outcome Measures

Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period.

Results

Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157 090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58–0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55–0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥80%) to statins were compared to those with good adherence to hypertension drugs (≥80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence.

Conclusions

5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50–80 years without prior hospitalizations for fractures.     

Does Childhood Sexual Abuse Predict Young Adult's BMI? A Birth Cohort Study

Objective: The objective was to identify the extent to which childhood sexual abuse (CSA) is associated with BMI and overweight status in young adulthood and to examine whether any associations differ by gender. Research Methods and Procedures: The Mater‐University of Queensland Study of Pregnancy is a prospective birth cohort from a population‐based sample involving 7223 singletons whose mothers were enrolled in the 1980s at the first antenatal visit. The present cohort consisted of a subgroup of 2461 young adults who had both self‐reported CSA data and measured BMI at 21 years. Results: Of 1273 men, 10.5% reported non‐penetrative and 7.5% reported penetrative CSA before age 16 years. Of 1305 women, 20.6% reported non‐penetrative and 7.9% reported penetrative CSA by age 16 years. We found young women's BMI and the prevalence of overweight at age 21 were greater in those who experienced penetrative CSA. This association was robust to adjustment for a variety of potential confounders. However, there was no association between non‐penetrative CSA and BMI in women and no association between either category of CSA and BMI in men. There was statistical evidence for a gender difference in the association of CSA with mean BMI at age 21 (p value for statistical interaction <0.01 in all models). Discussion: These findings suggest that among women, penetrative CSA is associated with greater BMI and increased odds of being overweight in later life, whereas in men, this association does not hold. This gender difference may reflect differences between women and men in the relationship between psychological trauma and body image or may be a chance subgroup finding.     

Does Social Capital Promote Physical Activity? A Population-Based Study in Japan

Background

To examine the association between individual-level social capital and physical activity.

Methodology/Principal Findings

In February 2009, data were collected in a population-based cross-sectional survey in Okayama city, Japan. A cluster-sampling approach was used to randomly select 4,000 residents from 20 school districts. A total of 2260 questionnaires were returned (response rate: 57.4%). Individual-level social capital was assessed by an item inquiring about perceived trust of others in the community (cognitive dimension of social capital) categorized as low trust (43.0%), mid trust (38.6%), and high trust (17.3%), as well as participation in voluntary groups (structural dimension of social capital), which further distinguished between bonding (8.9%) and bridging (27.1%) social capital. Using logistic regression, we calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for physical inactivity associated with each domain of social capital. Multiple imputation method was employed for missing data. Among total participants, 68.8% were physically active and 28.9% were inactive. Higher trust was associated with a significantly lower odds of physical inactivity (OR = 0.58, 95% CI = 0.42–0.79) compared with low trust. Both bridging and bonding social capital were marginally significantly associated with lower odds of physical inactivity (bridging, OR = 0.79, 95% CI = 0.62–1.00; bonding, OR = 0.71, 95% CI = 0.48–1.03) compared with lack of structural social capital.

Conclusions/Significance

Low individual-level social capital, especially lower trust of others in the community, was associated with physical inactivity among Japanese adults.     

Is There an Association between Long-Term Sick Leave and Disability Pension and Unemployment beyond the Effect of Health Status? – A Cohort Study

Background

Studies have shown that long-term sick leave is a strong predictor of disability pension. However, few have aimed to disentangle the effect of sick leave and of health status.The objective of this study was to investigate whether there is an association between long-term sick leave and disability pension and unemployment, when taking health status into account.

Methods/Principal Findings

The study was based on the Stockholm Public Health Cohort, restricted to 13,027 employed individuals (45.9% men) aged 18–59 in 2002 and followed until 2007.Hazard ratios (HR) with 95% Confidence Interval (CI) were estimated by Cox regression models adjusting for socio-demographic factors and five measures of health status.Having been on long-term sick leave increased the risk of disability pension (HR 4.01; 95% CI 3.19–5.05) and long-term unemployment (HR 1.45; 95% CI 1.05–2.00), after adjustment for health status. The analyses of long-term sick leave due to specific illness showed that the increased risk for long-term unemployment was confined to the group on sick leave due to musculoskeletal (HR 1.70 95% CI 1.00–2.89) and mental illness (HR 1.80 95% CI 1.13–2.88) and further that there was an increased risk for short-term unemployment in the group on sick leave due to mental illness (HR1.57 95%CI 1.09–2.26).

Conclusions/Significance

Long-term sick leave increases the risks of both disability pension and unemployment even when taking health status into account. The results support the hypothesis that long-term sick leave may start a process of marginalization from the labor market.     

Should Schools Expect Poor Physical and Mental Health,Social Adjustment,and Participation Outcomes in Students with Disability?

The literature on whether students with disabilities have worse physical and mental health, social adjustment, and participation outcomes when compared to their peers without disabilities is largely inconclusive. While the majority of case control studies showed significantly worse outcomes for students with disabilities; the proportion of variance accounted for is rarely reported. The current study used a population cross-sectional approach to determine the classification ability of commonly used screening and outcome measures in determining the disability status. Furthermore, the study aimed to identify the variables, if any, that best predicted the presence of disability. Results of univariate discriminant function analyses suggest that across the board, the sensitivity of the outcome/screening tools to correctly identify students with a disability was 31.9% higher than the related Positive Predictive Value (PPV). The lower PPV and Positive Likelihood Ratio (LR⁺) scores suggest that the included measures had limited discriminant ability (17.6% to 40.3%) in accurately identifying students at-risk for further assessment. Results of multivariate analyses suggested that poor health and hyperactivity increased the odds of having a disability about two to three times, while poor close perceived friendship and academic competences predicted disability with roughly the same magnitude. Overall, the findings of the current study highlight the need for researchers and clinicians to familiarize themselves with the psychometric properties of measures, and be cautious in matching the function of the measures with their research and clinical needs.     

Violence Affects Physical and Mental Health Differently: The General Population Based Troms? Study

This general population-based study examined associations between violence and mental health, musculoskeletal pain, and early disability pension. The prevalence and consequences of good vs. poor adjustment (resilience vs. vulnerability) following encounters with violence were also examined. Data were based on the sixth wave of the “Tromsø Study” (N = 12,981; 65.7% response rate, 53.4% women, M-age = 57.5 years, SD-age = 12.7 years). Self-reported data on psychological (threats) and physical violence (beaten/kicked), mental health (anxiety/depression), musculoskeletal pain (MSP), and granting of disability pension (DP) were collected. Men suffered more violent events during childhood than women did, and vice versa during adulthood. Psychological violence implied poorer mental health and slightly more MSP than physical violence. The risk of MSP was highest for violence occurring during childhood in women and during the last year for men. A dose-response relationship between an increasing number of violent encounters and poorer health was observed. About 58% of individuals reported no negative impact of violence (hence, resilience group), whereas 42% considered themselves as more vulnerable following encounters with violence. Regression analyses indicated comparable mental health but slightly more MSP in the resilience group compared to the unexposed group, whereas the vulnerable group had significantly worse health overall and a higher risk of early granting of DP. Resilience is not an all-or-nothing matter, as physical ailments may characterize individuals adapting well following encounters with violence.     

The Link between Inequality and Population Health in Low and Middle Income Countries: Policy Myth or Social Reality?

An influential policy idea states that reducing inequality is beneficial for improving health in the low and middle income countries (LMICs). Our study provides an empirical test of this idea: we utilized data collected by the Demographic and Health Surveys between 2000 and 2011 in as much as 52 LMICs, and we examined the relationship between household wealth inequality and two health outcomes: anemia status (of the children and their mothers) and the women'' experience of child mortality. Based on multi-level analyses, we found that higher levels of household wealth inequality related to worse health, but this effect was strongly reduced when we took into account the level of individuals'' wealth. However, even after accounting for the differences between individuals in terms of household wealth and other characteristics, in those LMICs with higher household wealth inequality more women experienced child mortality and more children were tested with anemia. This effect was partially mediated by the country''s level and coverage of the health services and infrastructure. Furthermore, we found higher inequality to be related to a larger health gap between the poor and the rich in only one of the three examined samples. We conclude that an effective way to improve the health in the LMICs is to increase the wealth among the poor, which in turn also would lead to lower overall inequality and potential investments in public health infrastructure and services.     

Concurrent Conditions in Patients with Chronic Constipation: A Population–Based Study

Background

Chronic constipation (CC) is a common condition but its concurrent conditions are not well characterized. We measured the prevalence and risk of developing 15 pre–specified concurrent conditions in patients with CC.

Methods

Retrospective cohort study using the Medicaid database of California, utilizing ICD-9 codes for detection of cases (CC), controls (patients with GERD) and concurrent conditions. Study period was 01/01/1995 to 06/30/2005. Index date was the date 3 months before the first physician visit for CC. Pre-index time (12 months) was compared to post-index time (12 months) to assess the association of every concurrent condition within each cohort. To account for ascertainment bias, an adjusted odds ratio was calculated by comparing the odds ratio for every concurrent condition in the CC cohort to that in the GERD cohort.

Results

147,595 patients with CC (mean age 54.2 years; 69.7% women; 36.2% white) and 142,086 patients with GERD (mean age 56.3 years; 65.3% women; 41.6% white) were evaluated. The most prevalent concurrent conditions with CC were hemorrhoids (7.6%), diverticular disease (5.9%), ano–rectal hemorrhage (4.7%), irritable bowel syndrome (3.5%) and fecal impaction (2%). When adjusted for ascertainment bias, the most notable associations with CC were Hirschsprung''s disease, fecal impaction and ano-rectal conditions such as fissure, fistula, hemorrhage and ulcers.

Conclusion

Chronic constipation is associated with several concurrent conditions of variable risk and prevalence. To reduce the overall burden of CC, these concurrent conditions need to be addressed.     

Who Needs Bereavement Support? A Population Based Survey of Bereavement Risk and Support Need

This study identifies and describes the profiles of bereavement risk and support needs of a community sample in Australia and tests the fit of the data with the three-tiered public health model for bereavement support. Family members who were bereaved 6–24 months prior to the survey and who were clients of four funeral providers participated (May-July 2013). A postal survey was used to collect information about bereaved people’s experience of caring and perceived satisfaction with any bereavement support provided. The questionnaire included a validated risk assessment screening measure for Prolonged Grief Disorder (PG-13). A total of 678 bereaved people responded. The model predicted that 60% of the sample would be low risk, 30% moderate risk, and 10% high risk. Actual figures were very close at 58.4%, 35.2% and 6.4% respectively. The analysis of the demographic characteristics, experience and impact of caring and bereavement, and satisfaction with support received from a variety of sources revealed differential experiences and needs that align with the expectation of low, moderate, and high bereavement support need, as articulated in the public health model. This is the first empirical test of the public health model of bereavement support. As there is a lack of clear evidence to guide development and allocation of bereavement support programs, the findings have the potential to inform the ability of services, community organizations and informal networks to prioritize care according to each level of bereavement need. This is essential to achieve cost-effective and equitable resource allocation.     

How Random Is Social Behaviour? Disentangling Social Complexity through the Study of a Wild House Mouse Population

Out of all the complex phenomena displayed in the behaviour of animal groups, many are thought to be emergent properties of rather simple decisions at the individual level. Some of these phenomena may also be explained by random processes only. Here we investigate to what extent the interaction dynamics of a population of wild house mice (Mus domesticus) in their natural environment can be explained by a simple stochastic model. We first introduce the notion of perceptual landscape, a novel tool used here to describe the utilisation of space by the mouse colony based on the sampling of individuals in discrete locations. We then implement the behavioural assumptions of the perceptual landscape in a multi-agent simulation to verify their accuracy in the reproduction of observed social patterns. We find that many high-level features – with the exception of territoriality – of our behavioural dataset can be accounted for at the population level through the use of this simplified representation. Our findings underline the potential importance of random factors in the apparent complexity of the mice''s social structure. These results resonate in the general context of adaptive behaviour versus elementary environmental interactions.     

On the Origin of Rheumatoid Arthritis: The Impact of Environment and Genes—A Population Based Twin Study

Background

Rheumatoid arthritis (RA) is an autoimmune disease with a complex origin. Previous studies have reported heritability estimates on RA at about 60%. Only 16% of the genetic background of the disease has been disclosed so far. The purpose of the present investigation was to provide an optimized estimate on the heritability of RA and to study the recurrence risk in a nationwide Caucasian twin population.

Methods and Findings

In a mail survey addressed to 56.707 twin individuals, RA was reported by 479 individuals, mean age 52 (range 16–73). Respondents underwent an interview and clinical examination. Ascertainment probability was 80%. RA was confirmed in 162 twin individuals yielding a prevalence at 0.37% (95% CI 0.31–0.43). The mean discordance time was 19 years (range 0–57). The concordance was 9.1% (95% CI 1.9 to 24.3) in MZ, 6.4% (95% CI 2.1 to 14.3) in DZss. The increased relative risk of attracting RA conditioned on having an affected cotwin compared to the background population risk was 24.6 to 35.4 in MZ twins and 17.3 to 31.6 in DZss twins. The correlation coefficients were 0.60 (0.33 to 0.78) in monozygotic (MZ) and 0.55 (0.33 to 0.72) in dizygotic same sexed (DZss) pairs. Twelve percent (95% CI 0–76%) of the phenotypic variance in the liability to RA was due to additive genetic effects, 50% (95% CI 0–72%) to shared environmental effects and 38% (95% CI 17–61%) to non-shared environmental effects.

Conclusions

This study emphasizes that family factors are important for the development of RA. Although genetic effectors are important, shared and non-shared environmental triggers and/or epigenetic stochastic events seem to be even more significant. However, it should be borne in mind that the genetic and non-genetic components may not be the same across disease subsets.     

Does Work Affect Personality? A Study in Horses

It has been repeatedly hypothesized that job characteristics are related to changes in personality in humans, but often personality models still omit effects of life experience. Demonstrating reciprocal relationships between personality and work remains a challenge though, as in humans, many other influential factors may interfere. This study investigates this relationship by comparing the emotional reactivity of horses that differed only by their type of work. Horses are remarkable animal models to investigate this question as they share with humans working activities and their potential difficulties, such as "interpersonal" conflicts or "suppressed emotions". An earlier study showed that different types of work could be associated with different chronic behavioural disorders. Here, we hypothesised that type of work would affect horses' personality. Therefore over one hundred adult horses, differing only by their work characteristics were presented standardised behavioural tests. Subjects lived under the same conditions (same housing, same food), were of the same sex (geldings), and mostly one of two breeds, and had not been genetically selected for their current type of work. This is to our knowledge the first time that a direct relationship between type of work and personality traits has been investigated. Our results show that horses from different types of work differ not as much in their overall emotional levels as in the ways they express emotions (i.e. behavioural profile). Extremes were dressage horses, which presented the highest excitation components, and voltige horses, which were the quietest. The horses' type of work was decided by the stall managers, mostly on their jumping abilities, but unconscious choice based on individual behavioural characteristics cannot be totally excluded. Further research would require manipulating type of work. Our results nevertheless agree with reports on humans and suggest that more attention should be given to work characteristics when evaluating personalities.     

Time Trend of Multiple Myeloma and Associated Secondary Primary Malignancies in Asian Patients: A Taiwan Population–Based Study

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78–1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79–21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.     

Gestational Age at Birth and ‘Body-Mind’ Health at 5 Years of Age: A Population Based Cohort Study

Numerous studies have identified the effects of prematurity on the neonate’s physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop. Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000–2002 in the United Kingdom) was performed. Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children’s general health and severity of behavior problems. The association between parent’s general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health. Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status. The greatest contribution to the childhood composite health measure at 5 years was for children born at 32–36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%–6.2%), compared to 1% (0.2–2.3) for birth at less than 32 weeks. Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems. The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies.     

The Association of Episiotomy with Obstetric Anal Sphincter Injury–A Population Based Matched Cohort Study

Objectives

To estimate the independent association of episiotomy with obstetric anal sphincter injuries (OASIS) using first a cross-sectional and then a matched pair analysis.

Design

A matched cohort.

Setting

Data was gathered from the Finnish Medical Birth Register from 2004–2011.

Population

All singleton vaginal births (n = 303,758).

Methods

Women resulting matched pairs (n = 63,925) were matched based on baseline risk of OASIS defined based on parity (first or second/subsequent vaginal births), age, birth weight, mode of delivery, prior caesarean section, and length of active second stage of birth.

Results

In cross-sectional analysis episiotomy was associated with a 12% lower incidence of OASIS (adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.80 to 0.98) in first vaginal births and with a 132% increased incidence of OASIS in second or subsequent vaginal births (aOR 2.32, 95% CI 1.77 to 3.03). In matched pair analysis episiotomy was associated with a 23% (aOR 0.77, 95% CI 0.69 to 0.86) lower incidence of OASIS in first vaginal births and a 61% (aOR 1.61, 95% CI 1.14 to 2.29) increased incidence of OASIS in second or subsequent vaginal births compared to women who gave birth without an episiotomy. The matched pair analysis showed a 12.5% and a 31.6% reduction in aORs of OASIS associated with episiotomy, respectively.

Conclusions

A matched pair analysis showed a substantial reduction in the aORs of OASIS with episiotomy, due to confounding by indication. This indicates that results of observational studies evaluating an association between episiotomy and OASIS should be interpreted with caution.     

Can Insomnia in Pregnancy Predict Postpartum Depression? A Longitudinal,Population-Based Study

Background

Insomnia and depression are strongly interrelated. This study aimed to describe changes in sleep across childbirth, and to evaluate whether insomnia in pregnancy is a predictor of postpartum depression.

Methods

A longitudinal, population-based study was conducted among perinatal women giving birth at Akershus University Hospital, Norway. Women received questionnaires in weeks 17 and 32 of pregnancy and eight weeks postpartum. This paper presents data from 2,088 of 4,662 women with complete data for insomnia and depression in week 32 of pregnancy and eight weeks postpartum. Sleep times, wake-up times and average sleep durations were self-reported. The Bergen Insomnia Scale (BIS) was used to measure insomnia. The Edinburgh Postnatal Depression Scale (EPDS) was used to measure depressive symptoms.

Results

After delivery, sleep duration was reduced by 49 minutes (to 6.5 hours), and mean sleep efficiency was reduced from 84% to 75%. However, self-reported insomnia scores (BIS) improved from 17.2 to 15.4, and the reported prevalence of insomnia decreased from 61.6% to 53.8%. High EPDS scores and anxiety in pregnancy, fear of delivery, previous depression, primiparity, and higher educational level were risk factors for both postpartum insomnia and depression. Insomnia did not predict postpartum depression in women with no prior history of depression, whereas women who recovered from depression had residual insomnia.

Limitations

Depression and insomnia were not verified by clinical interviews. Women with depressive symptoms were less likely to remain in the study.

Conclusions

Although women slept fewer hours at night after delivery compared to during late pregnancy, and reported more nights with nighttime awakenings, their self-reported insomnia scores improved, and the prevalence of insomnia according to the DSM-IV criteria decreased. Insomnia in pregnancy may be a marker for postpartum recurrence of depression among women with previous depression.     

MDR-TB,Isolation, and Anomie: Has Anyone Referred to Social Work?

MDR-TB and admission to isolation can induce a situation in which individuals are normless, unable to achieve the social goals that they have learned to pursue. Described as anomie, this situation can induce deviant behaviour. Addressing the psychosocial ethics of MDR-TB and isolation, this paper responds to the call for consideration of resource allocation and liberty.     

Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study

Background

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.

Methods

All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services’ (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.

Results

64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5–16.5) vs. 31.0 for TBP (95% CI: 20.6–41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40–0.99, P = 0.045].

Conclusion

In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients.