Evolution of the endomembrane systems of trypanosomatids - conservation and specialisation.

Parasite surfaces support multiple functions required for survival within their hosts, and maintenance and functionality of the surface depends on membrane trafficking. To understand the evolutionary history of trypanosomatid trafficking, where multiple lifestyles and mechanisms of host interactions are known, we examined protein families central to defining intracellular compartments and mediating transport, namely Rabs, SNAREs and RabGAPs, across all available Euglenozoa genomes. Bodonids possess a large trafficking repertoire, which is mainly retained by the Trypanosoma cruzi group, with extensive losses in other lineages, particularly African trypanosomes and phytomonads. There are no large-scale expansions or contractions from an inferred ancestor, excluding direct associations between parasitism or host range. However, we observe stepwise secondary losses within Rab and SNARE cohorts (but not RabGAPs). Major changes are associated with endosomal and late exocytic pathways, consistent with the diversity in surface proteomes between trypanosomatids and mechanisms of interaction with the host. Along with the conserved core family proteins, several lineage-specific members of the Rab (but not SNARE) family were found. Significantly, testing predictions of SNARE complex composition by proteomics confirms generalised retention of function across eukaryotes.

Surgical skill and complication rates after bariatric surgery.

BACKGROUND: Clinical outcomes after many complex surgical procedures vary widely across hospitals and surgeons. Although it has been assumed that the proficiency of the operating surgeon is an important factor underlying such variation, empirical data are lacking on the relationships between technical skill and postoperative outcomes. METHODS: We conducted a study involving 20 bariatric surgeons in Michigan who participated in a statewide collaborative improvement program. Each surgeon submitted a single representative videotape of himself or herself performing a laparoscopic gastric bypass. Each videotape was rated in various domains of technical skill on a scale of 1 to 5 (with higher scores indicating more advanced skill) by at least 10 peer surgeons who were unaware of the identity of the operating surgeon. We then assessed relationships between these skill ratings and risk-adjusted complication rates, using data from a prospective, externally audited, clinical-outcomes registry involving 10,343 patients. RESULTS: Mean summary ratings of technical skill ranged from 2.6 to 4.8 across the 20 surgeons. The bottom quartile of surgical skill, as compared with the top quartile, was associated with higher complication rates (14.5% vs. 5.2%, P<0.001) and higher mortality (0.26% vs. 0.05%, P=0.01). The lowest quartile of skill was also associated with longer operations (137 minutes vs. 98 minutes, P<0.001) and higher rates of reoperation (3.4% vs. 1.6%, P=0.01) and readmission (6.3% vs. 2.7%) (P<0.001). CONCLUSIONS: The technical skill of practicing bariatric surgeons varied widely, and greater skill was associated with fewer postoperative complications and lower rates of reoperation, readmission, and visits to the emergency department. Although these findings are preliminary, they suggest that peer rating of operative skill may be an effective strategy for assessing a surgeon's proficiency.

Scalp cooling: a qualitative study to assess the perceptions and experiences of Australian patients with breast cancer.

PURPOSE: Chemotherapy-induced hair loss is a common and distressing side effect. Scalp cooling is increasingly being used to reduce this hair loss. The purpose of this study was to explore patients' perceptions and experience of scalp cooling. METHODS: Seventeen Australian women with a diagnosis of breast cancer participated in a focus group (n = 4) or a semi-structured interview (n = 3). Both scalp-cooled and non-scalp-cooled participant views were sought. Participant perceptions and experiences of scalp cooling were discussed as part of patients' overall chemotherapy experience and a thematic analysis conducted. RESULTS: Five themes emerged from the data: (1) scalp cooling in the context of treatment decision-making discussions, (2) hair loss expectations vs. experiences, (3) treatment-related expectations vs. experiences, (4) the promise of faster regrowth and (5) satisfaction with scalp cooling and future scalp cooling decision-making considerations. Information during treatment decision-making was the primary factor that influenced whether patient expectations were met. Faster regrowth was a motivator to continue treatment. Efficacy and tolerability of scalp cooling influenced future hypothetical treatment decision-making for both scalp-cooled and non-scalp-cooled participants. CONCLUSIONS: This study provides the first in-depth exploration of patient attitudes to scalp cooling. The results highlight a need for accurate information regarding efficacy and tolerability as well as hair care information to assist patients with their treatment decision-making.

Association Between Factor V Leiden Mutation, Small for Gestational Age, and Preterm Birth: A Systematic Review and Meta-Analysis.

OBJECTIVE: To estimate the association of a maternal factor V Leiden (FVL) mutation with SGA and preterm birth. DATA SOURCES: We performed a search of PubMed, Embase, Scopus, CINAHL, and the Cochrane Library from inception to April 2016 for cohort and case-control studies of women with FVL mutation and associated outcomes of SGA and preterm birth that included a reference group without FVL mutation. Additional studies were identified from reference lists of relevant research and review articles. STUDY SELECTION: Two authors (JKB, AMO) independently examined the abstracts of the potentially eligible studies, and full texts of eligible studies were retrieved for further evaluation. Disagreements were resolved by consensus. We identified 42 studies suitable for inclusion in the meta-analysis. DATA EXTRACTION: Thirty-two studies evaluated SGA, and 18 studies assessed preterm birth. Study quality was assessed using the Newcastle Ottawa Scale. A random effects model with inverse variance weighting was used to calculate pooled ORs and 95% CIs. Subgroup analyses were performed by study design. DATA SYNTHESIS: The overall OR associating FVL mutation with SGA was significant (OR 1.40, 95% CI 1.18 to 1.67). Analysis of 13 cohort studies resulted in an OR of 1.20 (95% CI 1.03 to 1.41), and data from 19 case-control studies yielded an OR of 1.86 (95% CI 1.35 to 2.56). There was no significant association between FVL mutation and preterm birth (OR 1.17, 95% CI 1.00 to 1.37) when all groups were studied, but the association was significant for case-control studies alone (OR 1.40, 95% CI 1.05 to 1.86). CONCLUSION: There is an increased risk for SGA in pregnancies complicated by FVL mutation in both cohort and case-control study designs. The risk of preterm birth with FVL mutation is less clear, although there is conflicting evidence from cohort and case-control studies regarding the risk of preterm birth associated with FVL mutation.

The influence of caregiver depression on children in non-relative foster care versus kinship care placements.

Little is known about how the challenges faced by caregivers influence the variation in social, emotional, and behavioral (SEB) outcomes of youth placed in kinship versus non-relative foster care. This study examined SEB symptoms among youth in kinship and non-relative foster care settings, hypothesizing that changes in caregiver depression would modify children's change in behavior over time. Child Behavior Checklist (CBCL) assessments of 199 children placed with kinship and non-relative foster care providers in a Mid-Atlantic city were conducted at time of placement and 6-12 months post-placement. Linear regression estimated CBCL change scores for youth across placement type and caregiver depression trajectories. Kinship caregivers were more likely to become depressed or remained depressed than non-relative foster caregivers. Youth in kinship care always exhibited better change in SEB outcomes than youth in non-relative foster care, but these positive outcomes were principally observed among families where caregivers demonstrated a reduction in depression over time or were never depressed. Adjusted change scores for non-relative foster care youth were always negative, with the most negative scores among youth whose caregivers became depressed over time. Caregiver well-being may modify the influence of placement setting on SEB outcomes for youth placed into out-of-home care. Findings lend to policy relevance for child welfare systems that seek kinship settings as a panacea to the challenges faced by youth, without allocating resources to address caregiver needs.

Professionally led support groups for people living with advanced or metastatic cancer: a systematic scoping review of effectiveness and factors critical to implementation success within real-world healthcare and community settings.

PURPOSE: To examine the effectiveness of professionally led support groups for people with advanced or metastatic cancer, and identify factors critical to implementation success within real-world settings. METHODS: Databases (MEDLINE; PsychINFO; CINAHL) and grey literature were searched for empirical publications and evaluations. Articles were screened for eligibility and data systematically extracted, charted and summarised using a modified scoping review methodology. Implementation factors were mapped using Proctor's implementation framework and the Consolidated Framework for Implementation Research 2.0. RESULTS: A total of 1691 publications were identified; 19 were eligible for inclusion (8 randomised controlled trials, 7 qualitative studies, 2 cohort studies, 2 mixed methods studies). Most (n=18) studies focused on tumour-specific support groups. Evidence supported professionally led support groups in reducing mood disturbances (n=5), distress (i.e. traumatic stress, depression) (n=4) and pain (n=2). Other benefits included social connectedness (n=6), addressing existential distress (n=5), information and knowledge (n=6), empowerment and sense of control (n=2), relationships with families (n=2) and communication with health professionals (n=2). Thirteen studies identified factors predicting successful adoption, implementation or sustainment, including acceptability (n=12; 63%), feasibility (n=6; 32%) and appropriateness (n=1; 5%). Key determinants of successful implementation included group leaders' skills/experience, mode of operation, travelling distance, group composition and membership and resourcing. CONCLUSIONS: Professionally led tumour-specific support groups demonstrate effectiveness in reducing mood disturbances, distress and pain among patients. Successful implementation hinges on factors such as leadership expertise, operational methods and resource allocation. IMPLICATIONS FOR CANCER SURVIVORS: Professionally led support groups may fill an important gap in supportive care for people with advanced or metastatic cancer.

The relationship of placement experience to school absenteeism and changing schools in young, school-aged children in foster care.

BACKGROUND: Chronic school absenteeism and frequent school changes, particularly among younger children, may be antecedents for the high rates of school failure and subsequent dropout among youth in foster care. However, the relationship of foster care experience to absenteeism and school change has not been well studied. OBJECTIVE: This study examined the association of placement experience with absenteeism and changing schools among 209 urban children in foster care enrolled in public elementary schools. METHODS: A cohort of children aged 5 to 8 years who entered non-relative or kinship foster care from 2006-2008 were followed longitudinally for 2 years from entry into foster care. Children residing in foster care were categorized at the end of the study as early stable, late stable, or unstable, if they achieved a permanent placement prior to 45 days, between 45 days and 9 months, or failed to do so within 9 months, respectively. Children who reunified home were classified as a fourth category. Poisson regression, controlling for baseline factors, was used to compare days absent and number of schools attended across categories of placement experience. RESULTS: Among the 209 children, 51% were male, 79% were African American, and 55% were initially placed with kin. One third of children reunified home; among children who did not reunify, one half was early stable, and a third was unstable. Adjusted rates of school absenteeism increased in stepwise fashion as children's placements became more unstable; children with unstable placements were 37% more likely to be absent than those with early placement stability (p=0.029). Children who reunified during the study demonstrated the highest rates of absenteeism; however, there was no significant difference in absenteeism before or after reunification. Number of schools attended increased as stability worsened, with the standardized rate of schools attended reaching 3.6 schools (95% CI 3.1-4.1) over a two year period among children in unstable placements. CONCLUSIONS: The relationship between placement experience and school absenteeism and school change illustrates the need to better coordinate the educational experience of high-risk children in foster care. The secondary finding of high absenteeism among children in the process of returning home illustrates that educational challenges for youth may be equally if not more concerning among the greater majority of youth in child welfare who remain home with birth parents.

The development of novel interventions to assist the leaders of cancer support groups.

PURPOSE: The literature on cancer support groups supports the provision of ongoing education and training for cancer support group leaders, with evidence suggesting that more skilled and experienced leaders create better outcomes for group members. To address support and training needs reported by leaders, three novel interventions were developed and pilot-tested. These included a leaders' website and discussion forum, DVD and manual, and a 2-day training workshop. METHODS: The interventions were developed using a combination of literature review, expert consensus, and consumer feedback. A convenience sample of ten leaders pilot-tested the Website and discussion forum. Using a mixed-method approach, evaluation of the workshop and the DVD and manual was conducted with 35 leaders. RESULTS: Overall, satisfaction with all aspects of the Website and discussion forum was high. Analysis of the quantitative data revealed extremely high satisfaction with the workshop and DVD and manual. The qualitative responses of workshop participants further supported the quantitative findings with enhanced knowledge, understanding, and confidence reported by leaders. CONCLUSIONS: All three interventions exhibited a high degree of user acceptance, regardless of the skill or experience of the cancer support group leader. The overall positive findings from the evaluation of the leader Website and discussion forum, the DVD and manual, and the workshop for cancer support group leaders provides evidence to support more rigorous evaluation of these resources in a randomized controlled trial.

Home visitation program effectiveness and the influence of community behavioral norms: a propensity score matched analysis of prenatal smoking cessation.

BACKGROUND: The influence of community context on the effectiveness of evidence-based maternal and child home visitation programs following implementation is poorly understood. This study compared prenatal smoking cessation between home visitation program recipients and local-area comparison women across 24 implementation sites within one state, while also estimating the independent effect of community smoking norms on smoking cessation behavior. METHODS: Retrospective cohort design using propensity score matching of Nurse-Family Partnership (NFP) clients and local-area matched comparison women who smoked cigarettes in the first trimester of pregnancy. Birth certificate data were used to classify smoking status. The main outcome measure was smoking cessation in the third trimester of pregnancy. Multivariable logistic regression analysis examined, over two time periods, the association of NFP exposure and the association of baseline county prenatal smoking rate on prenatal smoking cessation. RESULTS: The association of NFP participation and prenatal smoking cessation was stronger in a later implementation period (35.5% for NFP clients vs. 27.5% for comparison women, p < 0.001) than in an earlier implementation period (28.4% vs. 25.8%, p = 0.114). Cessation was also negatively associated with county prenatal smoking rate, controlling for NFP program effect, (OR = 0.84 per 5 percentage point change in county smoking rate, p = 0.002). CONCLUSIONS: Following a statewide implementation, program recipients of NFP demonstrated increased smoking cessation compared to comparison women, with a stronger program effect in later years. The significant association of county smoking rate with cessation suggests that community behavioral norms may present a challenge for evidence-based programs as models are translated into diverse communities.

Emergency department visits and hospitalizations for injuries among infants and children following statewide implementation of a home visitation model.

To compare hospital-based utilization for early childhood injuries between program recipients and local-area comparison families following statewide implementation of an evidence-based home visitation program, and to describe site-level program variation. Propensity score matching on baseline characteristics was used to create a retrospective cohort of Nurse-Family Partnership (NFP) clients and local area matched comparison women. The main outcome, a count of injury visit episodes, was enumerated from Medicaid claims for injuries examined in an emergency department or hospital setting during the first 2 years of life of children born to included subjects. Generalized linear models with a Poisson distribution examined the association between injury episode counts and NFP participation, controlling for other non-injury utilization and stratifying by individual agency catchment area in a fixed effects analysis. The children of NFP clients were more likely in aggregate to have higher rates of injury visits in the first 2 years of life than the children of comparison women (415.2/1,000 vs. 364.2/1,000, P < 0.0001). Significantly higher rates of visits among children of NFP clients for superficial injuries (156.6/1,000 vs. 132.6/1,000, P < 0.0001) principally accounted for the attributable difference in injury visit rates between groups. Among more serious injuries, no significant difference in injury visit rates was found between NFP clients and comparison women. The proportion of children with at least one injury visit varied from 14.5 to 42.5% among individual sites. Contrary to prior randomized trial data, no reductions in utilization for serious early childhood injuries were demonstrated following statewide implementation of an evidence-based home visitation program. Significant program variation on outcomes underscores the challenges to successful implementation.

How complex is GTPase signaling in trypanosomes?

Many signaling pathways in higher eukaryotes use Ras-like small GTPases. Here, we ask how complex are these small GTPase signaling pathways in trypanosomes? We seek to address this issue by comparisons with the representation of both the GTPase molecules and their accessory factors in several genomes.

Effect of NCAM on aged-related deterioration in vision.

The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging.

Genome of Leptomonas pyrrhocoris: a high-quality reference for monoxenous trypanosomatids and new insights into evolution of Leishmania.

Many high-quality genomes are available for dixenous (two hosts) trypanosomatid species of the genera Trypanosoma, Leishmania, and Phytomonas, but only fragmentary information is available for monoxenous (single-host) trypanosomatids. In trypanosomatids, monoxeny is ancestral to dixeny, thus it is anticipated that the genome sequences of the key monoxenous parasites will be instrumental for both understanding the origin of parasitism and the evolution of dixeny. Here, we present a high-quality genome for Leptomonas pyrrhocoris, which is closely related to the dixenous genus Leishmania. The L. pyrrhocoris genome (30.4 Mbp in 60 scaffolds) encodes 10,148 genes. Using the L. pyrrhocoris genome, we pinpointed genes gained in Leishmania. Among those genes, 20 genes with unknown function had expression patterns in the Leishmania mexicana life cycle suggesting their involvement in virulence. By combining differential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified several additional proteins potentially involved in virulence, including SpoU methylase and U3 small nucleolar ribonucleoprotein IMP3. The population genetics of L. pyrrhocoris was also addressed by sequencing thirteen strains of different geographic origin, allowing the identification of 1,318 genes under positive selection. This set of genes was significantly enriched in components of the cytoskeleton and the flagellum.

An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids.

African trypanosomes are evolutionarily highly divergent parasitic protozoa, and as a consequence the vast majority of trypanosome membrane proteins remain uncharacterised in terms of location, trafficking or function. Here we describe a novel family of type I membrane proteins which we designate 'invariant glycoproteins' (IGPs). IGPs are trypanosome-restricted, with extensive, lineage-specific paralogous expansions in related taxa. In T. brucei three IGP subfamilies, IGP34, IGP40 and IGP48 are recognised; all possess a putative C-type lectin ectodomain and are ER-localised, despite lacking a classical ER-retention motif. IGPs exhibit highest expression in stumpy stage cells, suggesting roles in developmental progression, but gene silencing in mammalian infective forms suggests that each IGP subfamily is also required for normal proliferation. Detailed analysis of the IGP48 subfamily indicates a role in maintaining ER morphology, while the ER lumenal domain is necessary and sufficient for formation of both oligomeric complexes and ER retention. IGP48 is detected by antibodies from T. b. rhodesiense infected humans. We propose that the IGPs represent a trypanosomatid-specific family of ER-localised glycoproteins, with potential contributions to life cycle progression and immunity, and utilise oligomerisation as an ER retention mechanism.

A qualitative assessment of psychosocial impact, coping and adjustment in high-risk melanoma patients and caregivers.

The present study qualitatively assessed the psychosocial impacts experienced by stage III melanoma patients and caregivers throughout the course of the disease, and the coping responses they utilized in an attempt to promote psychosocial adjustment. The purpose of the study was to inform the development of a supportive care strategy for this population. Nineteen stage III melanoma patients and 14 of their caregivers were recruited from the clinical research database of the Melanoma Institute Australia. Data were collected using semistructured telephone interviews and analysed using thematic analysis. Participants reported psychosocial impacts related to diagnosis (shock, panic and devastation), treatment (challenges and unsatisfactory care, pain and limitation, practical impacts, new roles and responsibilities for the caregiver, caregiver inadequacy) and survivorship (ongoing physical problems, watchful waiting, feeling abandoned). They also reported global themes relevant to multiple phases of the disease (emotional distress, disfigurement, injustice, caregiver devaluation). Coping responses were identified related to diagnosis (avoidance), treatment (confidence in the treatment team, taking action) and survivorship (finding a positive meaning, acceptance and moving on) as well as global themes pertaining to multiple disease phases (receiving support, helpful thinking, putting on a brave face, redirecting attention, religion). The current findings support routine screening for the presence of symptoms and psychological distress and appropriate referral when necessary, and for provision of psychosocial interventions to provide information and support to stage III melanoma patients and caregivers. In addition, provision of communication skills training to all health professionals treating melanoma, use of evidence-based strategies for improving patient/caregiver understanding and recall, and routine assessment of patient-reported outcomes to inform clinical practice would be helpful.

Evolution of Tre-2/Bub2/Cdc16 (TBC) Rab GTPase-activating proteins.

Rab GTPases serve as major control elements in the coordination and definition of specific trafficking steps and intracellular compartments. Rab activity is modulated in part by GTPase-activating proteins (GAPs), and many RabGAPs share a Tre-2/Bub2/Cdc16 (TBC)-domain architecture, although the majority of TBC proteins are poorly characterized. We reconstruct the evolutionary history of the TBC family using ScrollSaw, a method for the phylogenetic analysis of pan-eukaryotic data sets, and find a sophisticated, ancient TBC complement of at least 10 members. Significantly, the TBC complement is nearly always smaller than the Rab cohort in any individual genome but also suggests Rab/TBC coevolution. Further, TBC-domain architecture has been well conserved in modern eukaryotes. The reconstruction also shows conservation of ancestral TBC subfamilies, continuing evolution of new TBCs, and frequent secondary losses. These patterns give additional insights into the sculpting of the endomembrane system.

Exploring consent to randomized placebo-controlled clinical trials in oncology.

AIMS: Randomized placebo-controlled trials are critical for advancing knowledge in oncology, yet little is known about optimal communication for informed consent. This study aimed to identify patient preferences for and satisfaction with three consultation styles (information-focused, emotion-focused and collaborative) in simulated discussions of four clinical trial concepts (randomization, placebo, tissue analysis and oncologists' recommendation). METHODS: In total 75 Australian cancer patients and carers, or both, viewed videotaped simulated consultations with a doctor and patient discussing a randomized, placebo-controlled trial. Their satisfaction and preferences for both consultation style and information were assessed. The patients' characteristics and decision-making preferences were also evaluated as potential predictors for consultation style preference. RESULTS: Participants preferred a collaborative consultation style when discussing randomization (74.6%), placebo (71.4%) and oncologist's recommendation (77%). However an emotion-focused consultation style was preferred when discussing tissue analysis (81%). The participants represented a highly information-seeking group, although most favoured collaborative or passive roles in treatment decision-making. Limited variables were identified that predict consultation style preference. CONCLUSION: While supporting the value of a collaborative approach to clinical trial communications, the study finding that tissue analysis requires a more emotion-focused approach highlights a new focus for trial communication and confirms the need for doctors to remain flexible in their consultation style.

Evolution of the karyopherin-ß family of nucleocytoplasmic transport factors; ancient origins and continued specialization.

BACKGROUND: Macromolecular transport across the nuclear envelope (NE) is achieved through nuclear pore complexes (NPCs) and requires karyopherin-ßs (KAP-ßs), a family of soluble receptors, for recognition of embedded transport signals within cargo. We recently demonstrated, through proteomic analysis of trypanosomes, that NPC architecture is likely highly conserved across the Eukaryota, which in turn suggests conservation of the transport mechanisms. To determine if KAP-ß diversity was similarly established early in eukaryotic evolution or if it was subsequently layered onto a conserved NPC, we chose to identify KAP-ß sequences in a diverse range of eukaryotes and to investigate their evolutionary history. RESULTS: Thirty six predicted proteomes were scanned for candidate KAP-ß family members. These resulting sequences were resolved into fifteen KAP-ß subfamilies which, due to broad supergroup representation, were most likely represented in the last eukaryotic common ancestor (LECA). Candidate members of each KAP-ß subfamily were found in all eukaryotic supergroups, except XPO6, which is absent from Archaeplastida. Phylogenetic reconstruction revealed the likely evolutionary relationships between these different subfamilies. Many species contain more than one representative of each KAP-ß subfamily; many duplications are apparently taxon-specific but others result from duplications occurring earlier in eukaryotic history. CONCLUSIONS: At least fifteen KAP-ß subfamilies were established early in eukaryote evolution and likely before the LECA. In addition we identified expansions at multiple stages within eukaryote evolution, including a multicellular plant-specific KAP-ß, together with frequent secondary losses. Taken with evidence for early establishment of NPC architecture, these data demonstrate that multiple pathways for nucleocytoplasmic transport were established prior to the radiation of modern eukaryotes but that selective pressure continues to sculpt the KAP-ß family.

Variation in pregnancy outcomes following statewide implementation of a prenatal home visitation program.

OBJECTIVE: To examine, following statewide dissemination, the influence of an evidence-based home visitation program for first-time mothers on reductions of subsequent pregnancies across time and different locations. DESIGN: Retrospective cohort study. SETTING: Replication sites for the Nurse-Family Partnership (17 urban sites and 6 rural sites) across the Commonwealth of Pennsylvania between January 1, 2000, and December 31, 2007. PARTICIPANTS: A total of 3844 Nurse-Family Partnership clients matched by propensity score to 10 938 local-area controls. MAIN EXPOSURE: Program enrollment. MAIN OUTCOME MEASURE: Time to second pregnancy resulting in a live birth within 2 years of the first infant's birth. RESULTS: There were no program effects on time to first pregnancy in the early years of the program (2000-2003), but clients whose first infants were born after 2003 had fewer second pregnancies compared with controls (hazard ratio = 0.87; 95% confidence interval, 0.80-0.96). This benefit occurred principally among mothers who were aged 18 years or younger (hazard ratio = 0.73, 95% confidence interval, 0.61-0.89) and was twice as strong among mothers aged 18 years or younger from rural locations (hazard ratio = 0.40; 95% confidence interval, 0.22-0.73) compared with those from urban locations (hazard ratio = 0.79; 95% confidence interval, 0.65-0.95). CONCLUSIONS: Program effects on pregnancy planning emerged after an implementation period of 3 years in both urban and rural locations, but they were particularly strong in rural locations and among younger mothers.

Effect of surgical techniques on clinical outcomes after laparoscopic gastric bypass--results from the Michigan Bariatric Surgery Collaborative.

BACKGROUND: The techniques used with laparoscopic gastric bypass (LGB) and their association with patient outcomes remain largely unexplored. METHODS: We analyzed the data from the Michigan Bariatric Surgery Collaborative, which maintains a state-wide prospective clinical registry of bariatric surgery patients. Participating surgeons were surveyed regarding their use of specific techniques during LGB. The survey data were linked with the registry data from patients undergoing LGB from June 2006 to January 2010. The gastrojejunostomy technique and the use of staple-line reinforcement were evaluated for their effects on patient outcomes. RESULTS: During the study period, 9904 patients underwent LGB. A total of 44 surgeons (86%) completed the survey. When performing gastrojejunostomy, most surgeons used a circular stapler (CS) technique (66%), followed by the hand-sewn (HS) (18%) and linear stapler (LS) (16%). Also, 48% of surgeons reported using staple-line buttressing when creating the gastric pouch. The rate of anastomotic leak at the gastrojejunostomy was not affected by the surgical technique (CS .6%, LS .3%, HS .6%, P = .38). However, the CS technique was associated with a greater rate of postoperative hemorrhage (CS 2.9%, LS 1.2%, HS 1.6%, P <.0001) and wound infection (CS 4.7%, LS 1.6%, HS .6%, P <.0001). The use of staple-line reinforcement was associated with a lower rate of postoperative hemorrhage (1.9% versus 2.7%, P = .012). CONCLUSION: With LGB, the use of the CS technique was associated with greater rates of postoperative hemorrhage and wound infection than the use of the LS or HS technique. Furthermore, the use of staple-line reinforcement was associated with a reduction in the rates of postoperative hemorrhage.