Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

Recurrent Superior Mesenteric Artery Stent Fracture.

Ostial stenosis of the superior mesenteric artery (SMA) is usually a benign finding due to the significant collateralization inherent with visceral vessels. There is a subset of patients, however, with significant atherosclerotic disease leading to in situ thrombosis and subsequent mesenteric ischemia requiring intervention. Over the last 20 years, management of mesenteric ischemia-acute or chronic-has transitioned from an open embolectomy or bypass to an endovascular-first approach involving angioplasty and stenting. We are reporting a unique case of recurrent SMA stent fracture with imaging demonstrating diaphragmatic compression of the SMA during the respiratory cycle, subsequent management, and recommendations for future intervention.

Matrix remodeling associated 5 expression in trunk and limb during avian development.

Matrix remodeling associated 5 (MXRA5) is an extracellular protein that is upregulated in several cancers, but little is known regarding its spatial and temporal localization in the developing embryo. The present study was undertaken to investigate MXRA5 transcript expression in the trunk and limb of the embryonic chick to provide groundwork for future investigation of its developmental function. In situ hybridization utilizing digoxigenin-labeled sense control and experimental antisense probes was performed in paraffin sections of chick embryos from Hamburger and Hamilton (HH) stages 18-38. MXRA5 expression was initially low and restricted in extent at the earliest stages examined, but expression increased in strength and tissue distribution with developmental age. Transcripts were largely found in cells of mesodermal origin, including gut associated mesenchyme, tendon and ligament rudiments, intervertebral discs, dermal papillae of feather buds, heart valve precursors and leaflets, as well as in appendicular joint primordia. The present study has provided initial information on MXRA5 gene expression in the trunk and limb of early to mid-stage avian embryos. Results show that MXRA5 was expressed most strongly at sites undergoing change and remodeling of the extracellular matrix during transition of embryonic tissues into the functional adult morphology.

Differences in radial expansion force among inferior vena cava filter models support documented perforation rates.

OBJECTIVE: Inferior vena cava (IVC) filters are used in patients at risk for pulmonary embolism who cannot be anticoagulated. Unfortunately, these filters are not without risk, and complications include perforation, migration, and filter fracture. The most prevalent complication is filter perforation of the IVC, with incidence varying among filter models. To our knowledge, the mechanical properties of IVC filters have not been evaluated and are not readily available through the manufacturer. This study sought to determine whether differences in mechanical properties are similar to differences in documented perforation rates. METHODS: The radial expansion forces of Greenfield (Boston Scientific, Marlborough, Mass), Cook Celect (Cook Medical, Bloomington, Ind), and Cook Platinum filters were analyzed with three replicates per group. The intrinsic force exerted by the filter on the measuring device was collected in real time during controlled expansion. Replicates were averaged and significance was determined by calculating analysis of covariance using SAS software (SAS Institute, Cary, NC). RESULTS: Each filter model generated a significantly different radial expansion force (P < .001), and force was distributed at significantly different rates (P < .001) during expansion. The largest radial expansion force at minimal caval diameter was seen in the Cook Platinum filter, followed by the Cook Celect and Greenfield filters. Radial force dispersion during expansion was greatest in the Cook Celect, followed by the Cook Platinum and Greenfield filters. CONCLUSIONS: Differences in radial expansion forces among IVC filter models are consistent with documented perforation rates. Cook Celect IVC filters have a higher incidence of perforation compared with Greenfield filters when they are left in place for >90 days. Evaluation of Cook Celect filters yielded a significantly higher radial expansion force at minimum caval diameter, with greater force dispersion during expansion.

Instrumental variables as bias amplifiers with general outcome and confounding.

Drawing causal inference with observational studies is the central pillar of many disciplines. One sufficient condition for identifying the causal effect is that the treatment-outcome relationship is unconfounded conditional on the observed covariates. It is often believed that the more covariates we condition on, the more plausible this unconfoundedness assumption is. This belief has had a huge impact on practical causal inference, suggesting that we should adjust for all pretreatment covariates. However, when there is unmeasured confounding between the treatment and outcome, estimators adjusting for some pretreatment covariate might have greater bias than estimators without adjusting for this covariate. This kind of covariate is called a bias amplifier, and includes instrumental variables that are independent of the confounder, and affect the outcome only through the treatment. Previously, theoretical results for this phenomenon have been established only for linear models. We fill in this gap in the literature by providing a general theory, showing that this phenomenon happens under a wide class of models satisfying certain monotonicity assumptions. We further show that when the treatment follows an additive or multiplicative model conditional on the instrumental variable and the confounder, these monotonicity assumptions can be interpreted as the signs of the arrows of the causal diagrams.

Multiple robustness in factorized likelihood models.

We consider inference under a nonparametric or semiparametric model with likelihood that factorizes as the product of two or more variation-independent factors. We are interested in a finite-dimensional parameter that depends on only one of the likelihood factors and whose estimation requires the auxiliary estimation of one or several nuisance functions. We investigate general structures conducive to the construction of so-called multiply robust estimating functions, whose computation requires postulating several dimension-reducing models but which have mean zero at the true parameter value provided one of these models is correct.

Impact of a person-centred dementia care training programme on hospital staff attitudes, role efficacy and perceptions of caring for people with dementia: A repeated measures study.

BACKGROUND: People with dementia occupy up to one quarter of acute hospital beds. However, the quality of care delivered to this patient group is of national concern. Staff working in acute hospitals report lack of knowledge, skills and confidence in caring for people with dementia. There is limited evidence about the most effective approaches to supporting acute hospital staff to deliver more person-centred care. OBJECTIVES: This study aimed to evaluate the efficacy of a specialist training programme for acute hospital staff regarding improving attitudes, satisfaction and feelings of caring efficacy, in provision of care to people with dementia. DESIGN: A repeated measures design, with measures completed immediately prior to commencing training (T1), after completion of Foundation level training (T2: 4-6 weeks post-baseline), and following Intermediate level training (T3: 3-4 months post-baseline). SETTING: One NHS Trust in the North of England, UK. PARTICIPANTS: 40 acute hospital staff working in clinical roles, the majority of whom (90%) were nurses. METHODS: All participants received the 3.5 day Person-centred Care Training for Acute Hospitals (PCTAH) programme, comprised of two levels, Foundation (0.5 day) and Intermediate (3 days), delivered over a 3-4 months period. Staff demographics and previous exposure to dementia training were collected via a questionnaire. Staff attitudes were measured using the Approaches to Dementia Questionnaire (ADQ), satisfaction in caring for people with dementia was captured using the Staff Experiences of Working with Demented Residents questionnaire (SEWDR) and perceived caring efficacy was measured using the Caring Efficacy Scale (CES). RESULTS: The training programme was effective in producing a significant positive change on all three outcome measures following intermediate training compared to baseline. A significant positive effect was found on the ADQ between baseline and after completion of Foundation level training, but not for either of the other measures. CONCLUSIONS: Training acute hospital staff in Intermediate level person-centred dementia care is effective in producing significant improvements in attitudes towards and satisfaction in caring for people with dementia and feelings of caring efficacy. Foundation level training is effective in changing attitudes but does not seem to be sufficient to bring about change in satisfaction or caring efficacy.

Management of Acute Lower Gastrointestinal Bleeding: Principles and Current Practice in the United Kingdom.

Acute lower gastrointestinal bleeding (ALGIB) is a common cause for hospital admission that results in significant morbidity and mortality. The major objectives of all involved in the management of ALGBI patients are to reduce mortality and the need for major surgery. A secondary objective is to prevent unnecessary hospital admission for patients presenting with bleeding that is not life-threatening. The management of ALGBI has evolved over last decade with the changing modalities of diagnostic facilities. On review of the published literature, there is paucity of randomised control trials in relation to the diagnostic tools and management of ALGBI. The aim of this review is to summarise the principles and current methods available for the diagnosis and treatment of ALGIB and based on the available evidence and the current practice in the United Kingdom, outline an algorithm for the management of ALGIB.

Causal models for estimating the effects of weight gain on mortality.

Suppose, in contrast to the fact, in 1950, we had put the cohort of 18-year-old non-smoking American men on a stringent mandatory diet that guaranteed that no one would ever weigh more than their baseline weight established at the age of 18 years. How would the counterfactual mortality of these 18 year olds have compared to their actual observed mortality through 2007? We describe in detail how this counterfactual contrast could be estimated from longitudinal epidemiologic data similar to that stored in the electronic medical records of a large health maintenance organization (HMO) by applying g-estimation to a novel of structural nested model (SNM). Our analytic approach differs from any alternative approach in that, in the absence of model misspecification, it can successfully adjust for (i) measured time-varying confounders such as exercise, hypertension and diabetes that are simultaneously intermediate variables on the causal pathway from weight gain to death and determinants of future weight gain, (ii) unmeasured confounding by undiagnosed preclinical disease (that is, reverse causation) that can cause both poor weight gain and premature mortality (provided an upper bound can be specified for the maximum length of time a subject may suffer from a subclinical illness severe enough to affect his weight without the illness becomes clinically manifest) and (iii) the presence of particular identifiable subgroups, such as those suffering from serious renal, liver, pulmonary and/or cardiac disease, in whom confounding by unmeasured prognostic factors is so severe as to render useless any attempt at direct analytic adjustment. However, (ii) and (iii) limit the ability to empirically test whether the SNM is misspecified. The other two g-methods--the parametric g-computation algorithm and inverse probability of treatment weighted estimation of marginal structural models--can adjust for potential bias due to (i) but not due to (ii) or (iii).

Oxygen tension directs the differentiation pathway of human cytotrophoblast cells.

During placental development, human cytotrophoblast cells can differentiate to either villous syncytiotrophoblast cells or invasive extravillous trophoblast cells. We hypothesize that oxygen tension plays a critical role in determining the pathway of cytotrophoblast differentiation. A highly purified preparation of cytotrophoblast cells from human third trimester placenta was cultured for 5 days in either 20% or 1% oxygen tension. The cells incubated at 20% oxygen formed a syncytium as determined by immunohistochemistry using an anti-desmosomal protein antibody that identifies cell membranes. In addition, the mRNA was markedly induced for syncytin, a glycoprotein shown to be essential for syncytiotrophoblast formation, and for human placental lactogen (hPL), which is a specific marker for syncytiotrophoblast cells. In contrast, the cell incubated at 1% oxygen tension did not fuse by morphologic analysis and did not express syncytin or hPL mRNA. However, these cells expressed abundant amounts of HLA-G, a specific marker for extravillous trophoblast cells, which was not seen in cells incubated at 20% oxygen tension. These results suggest that low oxygen tension directs differentiation along the extravillous trophoblast cell pathway while greater oxygen tension directs differentiation along the villous trophoblast cell pathway.

First trimester maternal blood rheology and pregnancy induced hypertension.

This study evaluates the relationship between the first trimester assessment of maternal rheology and the subsequent development of pregnancy induced hypertension. This is a prospective observational study based in the Glasgow Royal Maternity Hospital, Scotland. From an original population of 744 consecutive antenatal attendees a total of 579 women were booked at less than 14 weeks' gestation. The main study group is a further subset comprising 251 primigravid women booking with a singleton pregnancy without essential hypertension. Previously published data from a group of non-pregnant women of similar age drawn from the same local community was used for external comparison. Blood samples were collected at the booking visit, from which fibrinogen, red cell aggregation, haematocrit and plasma, whole blood, relative and corrected viscosities were recorded. Information was obtained from the case notes in retrospect starting approximately 1 year after the first patients had first been recruited into the trial. The overall outcome of the pregnancies was noted with particular reference to pregnancy induced hypertension (PIH), birth weight, antepartum haemorrhage, pre-term labour, perinatal death, condition at delivery and neonatal complication. Our results show PIH is associated with a significantly raised mean blood viscosity and fibrinogen at time of booking. All significance disappears after adjustment for smoking, diastolic blood pressure and age. Viscosity is, however, only marginally non-significant (p = 0.07). In conclusion, blood rheology, in particular blood viscosity and fibrinogen, may play a predictive role in the development of pregnancy-induced hypertension. When combined with measurement of smoking and diastolic blood pressure at booking, these measurements could be used to calculate a risk score for the development of PIH, allowing targeting of antenatal care. Further data is required.

Origins and dispersals of Pacific peoples: evidence from mtDNA phylogenies of the Pacific rat.

The human settlement of the Pacific in general, and the origin of the Polynesians in particular, have been topics of debate for over two centuries. Polynesian origins are most immediately traced to people who arrived in the Fiji, Tonga, and Samoa region approximately 3,000 B.P. and are clearly associated with the Lapita Cultural Complex. Although this scenario of the immediate origins of the Polynesians is generally accepted, the debate on the ultimate origin of the Polynesians and the Lapita cultural complex continues. Our previous research has shown that analyses of mtDNA variation in the Pacific rat (Rattus exulans), often transported as a food item in the colonizing canoes, are valuable for tracing prehistoric human migration within Polynesia. Here we present mtDNA phylogenies based on approximately 240 base pairs of the d-loop from both archaeological and modern samples collected from Island Southeast Asia and the Pacific. We identify three major haplogroups, two of which occur in the Pacific. Comparing our results with Lapita models of Oceanic settlement, we are able to reject two often cited but simplistic models, finding support instead for multifaceted models incorporating a more complex view of the Lapita intrusion. This study is unique and valuable in that R. exulans is the only organism associated with the Lapita dispersal for which there are sufficient ancient and extant populations available for genetic analysis. By tracking population changes through time, we can understand more fully the settlement process and population interactions in both Near and Remote Oceania.

A costed profile audit of the surgical management of female stress incontinence.

BACKGROUND AND AIMS: To conduct a profile audit of three surgical treatments for urinary stress incontinence through the application of an episode costing process. METHODS: Four stage methodology: (1) construction or a profile of care for each of the surgical approaches (setting the standard); 2) calculation of a theoretical profile cost; (3) calculation of the observed costs from real patient episodes; (4) comparison of observed costs with profile costs, (comparing present practice with established standard). RESULTS: Profiles of care were constructed and compared with 39 actual in-patient episodes. Tension free vaginal tape (TVT Gynecare) is the cheapest modality of treatment in terms of both the expected profile cost and also observed (real patient) cost. Colposuspension is the most expensive form of treatment with real costs significantly greater than the expected profile. Clinical issues such as length of stay, duration of surgery, patient selection and complication rates were revealed through the exception reporting process. Length of stay is the main determinant of overall cost. CONCLUSION: It is possible to construct a costed and auditable standard of care for a surgical procedure. This standard can be compared with real patient costs calculated using the same methodology. Exception reporting based on differences between expected and real costs can be used to facilitate the audit of clinical practice. The technique is limited, however, by the need to collect accurate and detailed activity data.

Subclinical effects and fenbendazole treatment of turkey ascaridiasis under simulated field conditions.

Under simulated natural conditions of bird production and parasite challenge, the effects of ascaridiasis and the effectiveness of fenbendazole treatment (6-day regimes in the feed at 16 ppm) were documented. Birds were artificially challenged with ascarid larvae on a daily basis from day 35 to 112, with bird grow out ending on day 119. Experimental groups, on a per pen basis, were infected control, treated with fenbendazole at days 63-69, treated with fenbendazole at days 63-69 and days 91-97, and uninfected control. In the same order as above, and on an experimental group mean bird basis, final weights were 13.34, 13.47, 13.59, and 13.78 kg, average daily gains from day 7 to day 119 were 117.8, 118.9, 120.1, and 121.8 g, and units gained per unit of feed consumed from day 7 to day 119 were 0.337, 0.341, 0.347, and 0.362. Infected control bird mean Ascaridia dissimilis burdens, with all stages combined, ranged from 351.1 on day 63 to 117.2 on day 91, levels seen commonly with naturally infected commercial turkeys. Trial data dearly indicated that moderate A. dissimilis burdens negatively impacted animal performance (average daily gains and feed efficiencies) and that these parasite burdens are effectively removed by fenbendazole treatment.

Inference in randomized studies with informative censoring and discrete time-to-event endpoints.

In this article, we present a method for estimating and comparing the treatment-specific distributions of a discrete time-to-event variable from right-censored data. Our method allows for (1) adjustment for informative censoring due to measured prognostic factors for time to event and censoring and (2) quantification of the sensitivity of the inference to residual dependence between time to event and censoring due to unmeasured factors. We develop our approach in the context of a randomized trial for the treatment of chronic schizophrenia. We perform a simulation study to assess the practical performance of our methodology.

Racial and economic demographics of couples seeking infertility treatment.

OBJECTIVE: We characterized new infertility patients on the basis of race and economic factors. STUDY DESIGN: A retrospective chart review was performed of all patients seeking infertility evaluation from 1998 to 1999 at two infertility centers in Cincinnati, Ohio. Patients were categorized by race (white, black, or other). Statistics were analyzed by chi2 and logistic regression. RESULTS: Of 756 patients, 85.2% were white, 10.2% were black, and 4.4% were other. Infertility diagnoses were placed into the following 7 categories: ovarian, salpingitis, surgical sterilization, male factor, endometriosis, unexplained, and other. Black women had significantly more salpingitis than did nonblack women (P <.001) regardless of insurance status. However, surgical sterilization was more prevalent in patients without insurance regardless of race (P <.001). CONCLUSIONS: Our findings are consistent with previous studies showing that black women have more risk factors for salpingitis. Surgical sterilization risk factors were concordant with those of the National Center for Health Statistics.