Skin-to-skin contact for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Skin-to-skin contact between mother and infant after birth is recommended to promote breastfeeding and maternal-infant bonding. However, its impact on the incidence of neonatal hypoglycaemia is unknown. We conducted a systematic review and meta-analysis to assess this. METHODS: Published randomised control trials (RCTs), quasi-RCTs, non-randomised studies of interventions, cohort, or case-control studies with an intervention of skin-to-skin care compared to other treatment were included without language or date restrictions. The primary outcome was neonatal hypoglycaemia (study-defined). We searched 4 databases and 4 trial registries from inception to May 12th, 2023. Quality of studies was assessed using Cochrane Risk of Bias 1 or Effective Public Health Practice Project Quality Assessment tools. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results were synthesised using RevMan 5.4.1 or STATA and analysed using random-effects meta-analyses where possible, otherwise with direction of findings tables. This review was registered prospectively on PROSPERO (CRD42022328322). RESULTS: This review included 84,900 participants in 108 studies, comprising 65 RCTs, 16 quasi-RCTs, seven non-randomised studies of intervention, eight prospective cohort studies, nine retrospective cohort studies and three case-control studies. Evidence suggests skin-to-skin contact may result in a large reduction in the incidence of neonatal hypoglycaemia (7 RCTs/quasi-RCTs, 922 infants, RR 0.29 (0.13, 0.66), p < 0.0001, I2 = 47%). Skin-to-skin contact may reduce the incidence of admission to special care or neonatal intensive care nurseries for hypoglycaemia (1 observational study, 816 infants, OR 0.50 (0.25-1.00), p = 0.050), but the evidence is very uncertain. Skin-to-skin contact may reduce duration of initial hospital stay after birth (31 RCTs, 3437 infants, MD -2.37 (-3.66, -1.08) days, p = 0.0003, I2 = 90%, p for Egger's test = 0.02), and increase exclusive breastmilk feeding from birth to discharge (1 observational study, 1250 infants, RR 4.30 (3.19, 5.81), p < 0.0001), but the evidence is very uncertain. CONCLUSION: Skin-to-skin contact may lead to a large reduction in the incidence of neonatal hypoglycaemia. This, along with other established benefits, supports the practice of skin-to-skin contact for all infants and especially those at risk of hypoglycaemia.

Systematic Literature Review to Identify Cost and Resource Use Data in Patients with Early-Stage Non-small Cell Lung Cancer (NSCLC).

BACKGROUND: Approximately 2 million new cases and 1.76 million deaths occur annually due to lung cancer, with the main histological subtype being non-small cell lung cancer (NSCLC). The costs and resource use associated with NSCLC are important considerations to understand the economic impact imposed by the disease on patients, caregivers and healthcare services. OBJECTIVE: The objective of this systematic literature review (SLR) is to provide a comprehensive overview of the available direct medical costs, direct non-medical costs, indirect costs, cost drivers and resource use data available for patients with early-stage NSCLC. METHODS: Electronic searches were conducted via the Ovid platform in March 2021 and June 2022 and were supplemented by grey literature searches. Eligible patients had early-stage (stage I-III) resectable NSCLC and received treatment in the neoadjuvant or adjuvant setting. There was no restriction on intervention or comparators. Publication date was restricted to 2011 onwards, and English language publications or non-English language publications with an English abstract were of primary interest. Due to the anticipation of many studies meeting the inclusion criteria, analyses were restricted to full publications from countries of primary interest (Australia, Brazil, Canada, China, France, Germany, Italy, Japan, South Korea, Spain, UK and the US) and those with > 200 patients. The Molinier checklist was applied to conduct quality assessment. RESULTS: Forty-two full publications met the eligibility criteria and were included in this SLR. Early-stage NSCLC was associated with significant direct medical costs and healthcare utilisation, and the economic burden of the disease increased with its progression. Surgery was the primary cost driver in stage I patients, but as patients progressed to stage II and III, treatments such as chemotherapy and radiotherapy, and inpatient care became the main cost drivers. There was no significant difference in resource use between patients with early-stage disease. However, these data were heavily US-centric and there was a paucity of data relating to direct non-medical and indirect costs associated with early-stage NSCLC. CONCLUSIONS: Preventing disease progression for patients with NSCLC could reduce the economic burden of NSCLC on patients, caregivers and healthcare systems. This review provides a comprehensive overview of the available cost and resource use data in this indication, which is important in guiding the decisions of policy makers regarding the allocation of resources. However, it also indicates a need for more studies comparing the economic impact of NSCLC in markets in addition to the US.

Health State Utility Values in Early-Stage Non-small Cell Lung Cancer: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the predominant histological subtype of lung cancer and is the leading cause of cancer-related deaths globally. Quality of life is an important consideration for patients and current treatments can adversely affect health-related quality of life (HRQoL). OBJECTIVE: The objectives of this systematic literature review (SLR) were to identify and provide a comprehensive catalogue of published health state utility values (HSUVs) in patients with early-stage NSCLC and to understand the factors impacting on HSUVs in this indication. METHODS: Electronic searches of Embase, MEDLINE and Evidence-Based Medicine Reviews were conducted via the Ovid platform in March 2021 and June 2022 and were supplemented by grey literature searches of conference proceedings, reference lists, health technology assessment bodies, and other relevant sources. Eligibility criteria were based on patients with early-stage (stage I-III) resectable NSCLC receiving treatment in the adjuvant or neoadjuvant setting. No restriction was placed on interventions or comparators, geography, or publication date. English language publications or non-English language publications with an English abstract were of primary interest. A validated checklist was applied to conduct quality assessment of the full publications. RESULTS: Twenty-nine publications (27 full publications and two conference abstracts) met all eligibility criteria and reported 217 HSUVs and seven disutilities associated with patients with early NSCLC. The data showed that increasing disease stage is associated with decreasing HRQoL. It was also indicated that utility values vary by treatment approach; however, the choice of treatment may be influenced by the patients' disease stage at presentation. Few studies aligned with the requirements of health technology assessment (HTA) bodies, indicating a need for future studies to conform to these preferences, making them suitable for use in economic evaluations. CONCLUSIONS: This SLR found that disease stage and treatment approach were two of several factors that can impact patient-reported HRQoL. Additional studies are warranted to confirm these findings and to investigate emerging therapies for early NSCLC. In collecting a catalogue of HSUV data, this SLR has begun to identify the challenges associated with identifying reliable utility value estimates suitable for use in economic evaluations of early NSCLC.

Products of chickpea processing as texture improvers in gluten-free bread.

Recent market developments raised the need for alternatives to hydrocolloids as texture improver in gluten-free bread. Chickpea exerts several physicochemical properties (water- and oil-binding, emulsifying and foaming) that might address this need. Therefore, the effect of processing on chickpea functionality was tested on low ingredient dose, comparably to that of common hydrocolloids. Control bread was small, hard and with low gas retention ability as shown by microscopy, depicting holes inside crumb pores. Addition of chickpea flour in low dose (2% w/w) enhanced loaf volume by 20% and reduced crumb hardness by 40%, due to increased gas retention (no holes within pores) and superior homogeneity of the starch-protein network. On the contrary, chickpea paste deleteriously affected bread quality due to loss of solubility upon cooking. Interestingly, both soaking and cooking water significantly reduced crumb hardness, although to a lower extent than the flour. More homogeneous crumb structure and gas retention were observed in the micrographs, possibly due to the emulsifying activity of flavonoids and saponins (soaking) and insoluble fibre (cooking). Chickpea ingredients are promising substitute of hydrocolloids such as xanthan gum for texture improvement of gluten-free bread, although acting with different mechanisms.

Impact of faecal occult blood test screening on emergency admissions and short-term outcomes for colorectal cancer.

BACKGROUND: Small studies have examined the effect of faecal occult blood test (FOBT) screening on the proportion of hospital admissions for colorectal cancer (CRC) classed as an emergency. This study aimed to examine this and short-term outcomes in persons invited for screening compared with a control group not invited. METHODS: The invited group comprised all individuals invited between 1 April 2000 and 31 July 2007 in the Scottish arm of the UK demonstration pilot of FOBT, and subsequently diagnosed with CRC aged 50-72 years between 1 May 2000 and 31 July 2009. The controls comprised all remaining individuals in Scotland not invited for FOBT but diagnosed with CRC aged 50-72 years in the same period. RESULTS: There were 2981 people diagnosed with CRC in the group invited for screening (58·3 per cent participated) and 9842 in the control group. Multivariable regression adjusted for sex, age, deprivation, co-morbidities, tumour site and Dukes' stage showed no difference between the groups for emergency admissions (odds ratio (OR) 0·89, 95 per cent confidence interval (c.i.) 0·77 to 1·02; P = 0·084) or length of hospital stay (LOS) (ß coefficient -1·02 (95 per cent c.i. -1·05 to 1·01) days; P = 0·226). Comparing participants with controls, there were fewer emergency admissions (OR 0·59, 0·49 to 0·71; P < 0·001) and shorter LOS (ß coefficient -1·06 (-1·10 to -1·02) days; P = 0·001). Short-term mortality was lower in the screened than the non-screened population (1·1 versus 2·8 per cent; P = 0·001). CONCLUSION: People who participated in FOBT screening had fewer emergency admissions and a shorter LOS. Deprivation was associated negatively with participation, but the impact of FOBT participation on emergency admissions was independent of deprivation level. The reduction in LOS has potential to reduce financial costs.

Patterns of uptake in a biennial faecal occult blood test screening programme for colorectal cancer.

AIM: The patterns of response in faecal occult blood test (FOBT) screening were studied. METHOD: A total of 251,578 people invited three times for faecal occult blood testing were categorized according to how they responded to the invitations, as follows: YNN, NYN, NNY, NYY, YNY, YYN, YYY or NNN (Y = response; N = no response). RESULTS: Overall, 163,038 (64.8%) responded at least once, and of those the biggest category was YYY (98,494, 60.4%). Of 1927 cancers diagnosed in the age group eligible for screening, there were 405 screen-detected cancers, 529 interval cancers and 993 cancers arising in people who had not been screened for over 2 years (i.e. falling outside the interval cancer category). In the YYY group, 79 screen-detected cancers would have been missed had the members of this group responded YNN and 65 had they responded YYN. In the YYN group, 104 screening cancers would have been missed if they had followed the YNN pattern. In most cases, the screen-detected cancers were diagnosed at the last invitation accepted, indicating that, after a diagnosis of cancer, further screening invitations were rarely accepted. Accordingly, the numbers of screen-detected and interval cancers were adjusted for likely pattern of response according to the proportion of the whole population falling into each pattern. With this adjustment, 40.9% of the cancers in the YYY group were screen detected compared with 29.3% in the YYN group and 20.7% in the YNN group (P < 0.001). Among those who responded once, twice and three times, the stage distribution of screen-detected cancers was similar, indicating that the prognosis of screen-detected cancer is unlikely to be poorer if not detected at the first screen. CONCLUSION: This study is the first to examine patterns of response to screening invitations and confirms the importance to individuals of continuing to accept repeated screening invitations.

The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study.

BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000-2007) before the roll out of a national programme. All residents (50-69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83-0.99) overall and 0.73 (95% CI 0.65-0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06-1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants.

Negative screening colonoscopy after a positive guaiac faecal occult blood test: not a contraindication to continued screening.

AIM: In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed. METHOD: Data on participants aged 50-69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland. RESULTS: In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re-invited in the second round, 905 accepted, and 157 had a positive gFOBT result, giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. In the third screening round 1031 were invited for a third time and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. Eighty-four were invited for a third gFOBT, 66 accepted and 19 (25.6%) had a positive result none of whom had an adenoma or carcinoma. CONCLUSION: These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies.

'Idiopathic' intestinal failure--the importance of identifying and treating primary psychopathology.

BACKGROUND: Gastrointestinal neuromuscular disorders (GINMD) are an important cause of intestinal failure (IF). We present six cases of IF in whom a diagnosis of GINMD was initially suspected, but in whom psychopathology was discovered to be the primary etiology. METHODS: (i) Six consecutive cases referred to our unit with IF, initially presumed to be due to GINMD, were selected. Informed consent was obtained from all patients. Case notes were reviewed for salient clinical information. (ii) A literature search was performed to ascertain the epidemiology of psychopathology in IF and the current evidence for the management of severe functional GI disorders with a multidisciplinary psychiatric approach. KEY RESULTS: (i)All six cases required multidisciplinary psychiatric management in a specialized psychiatric unit that included the use of antidepressants, antipsychotics, mood stabilizers, and Electroconvulsive therapy in addition to nutritional support via enteral or parenteral routes. (ii) The evidence base for the treatment of severe FGIDs is sparse. CONCLUSIONS & INFERENCES: There is a need for additional reporting of such cases and further research. Our experience would suggest that a delay in the involvement of a specialist liaison psychiatrist has the potential to be life threatening in such cases. This may be more likely with greater severity, where the apparent predominance of 'physical' symptoms generates reluctance in both patient and physician to consider a psychiatric etiology and also appears to occur due to a lengthier investigative process than existed previously. We therefore propose that the provision of a specialist psychiatric assessment for all patients presenting with IF is indicated at the point of initial clinical contact, based upon the substantial clinical benefit it has the potential to confer upon a significant minority. This process need not delay investigation, which can continue as indicated in parallel, but can be life-saving.

Interval cancers in a FOBT-based colorectal cancer population screening programme: implications for stage, gender and tumour site.

BACKGROUND: Between 2000 and 2007, a demonstration pilot of biennial guaiac faecal occult blood test (GFOBT) screening was carried out in Scotland. METHODS: Interval cancers were defined as cancers diagnosed within 2 years (ie, a complete screening round) of a negative GFOBT. The stage and outcome of the interval cancers were compared with those arising contemporaneously in the non-screened Scottish population. In addition, the gender and site distributions of the interval cancers were compared with those in the screen-detected group and the non-screened population. RESULTS: Of the cancers diagnosed in the screened population, interval cancers comprised 31.2% in the first round, 47.7% in the second, and 58.9% in the third, although this was due to a decline in the numbers of screen-detected cancers rather than an increase in interval cancers. There were no consistent differences in the stage distribution of interval cancers and cancers from the non-screened population, and, in all three rounds, both overall and cancer-specific survival were significantly better for patients diagnosed with interval cancers (p<0.01). The percentage of cancers arising in women was significantly higher in the interval cancer group (50.2%) than in either the screen-detected group (35.3%, p<0.001) or the non-screened group (40.6%, p<0.001). In addition, the proportion of both right-sided and rectal cancers was significantly higher in the interval cancer group than in either the screen-detected (p<0.001) or non-screened (p<0.004) groups. CONCLUSIONS: Although GFOBT screening is associated with substantial interval cancer rates that increase with screening round, the absolute numbers do not. Interval cancers are associated with a better prognosis than cancers arising in a non-screened population, and GFOBT appears to preferentially detect cancers in men and the left side of the colon at the expense of cancers in women and in the right colon and rectum.

Effect of repeated invitations on uptake of colorectal cancer screening using faecal occult blood testing: analysis of prevalence and incidence screening.

OBJECTIVE: To analyse the effects of prevalence and incidence screening on uptake and detection of cancer in an ongoing, dynamic programme for colorectal screening using faecal occult blood testing. DESIGN: Analysis of prevalence and incidence screening. SETTING: Three rounds of biennial colorectal screening using the guaiac faecal occult blood test in east and north east Scotland, March 2000 to May 2007. PARTICIPANTS: Adults aged 50-69. MAIN OUTCOME MEASURES: Uptake of screening, test positivity (percentage of those invited who returned a test that was positive and triggered an invitation for colonoscopy), positive predictive value, and stage of cancer. RESULTS: Of 510 990 screening episodes in all three rounds, 248 998 (48.7%) were for prevalence, 163 483 (32.0%) were for first incidence, and 98 509 (19.3%) were for second incidence. Uptake of a first invitation for prevalence screening was 53% and for a second and third invitation was 15% and 12%. In the cohort invited for the first round, uptake of prevalence screening rose from 55% in the first round to 63% in the third. The uptake of first incidence screening on a first invitation was 54% and on a second invitation was 86% and on a first invitation for second incidence screening was 46%. The positivity rate in prevalence screening was 1.9% and the uptake of colonoscopy was 87%. The corresponding values for a first incidence screen were 1.7% and 90% and for a second incidence screen were 1.1% and 94.5%. The positive predictive value of a positive faecal occult blood test result for cancer was 11.0% for prevalence screening, 6.5% for the first incidence screen, and 7.5% for the second incidence screen. The corresponding values for the positive predictive value for adenoma were 35.5%, 29.4%, and 26.7%. The proportion of cancers at stage I dropped from 46.5% for prevalence screening to 41% for first incidence screening and 35% for second incidence screening. CONCLUSIONS: Repeat invitations to those who do not take up the offer of screening increases the number of those who accept, for both prevalence screening and incidence screening. Although the positive predictive value for both cancer and adenomas fell between the prevalence screen and the first incidence screen, they did not fall between the first and second incidence screens. The deterioration in cancer stage from prevalence to incidence screening suggests that some cancers picked up at incidence screening may have been missed on prevalence screening, but the stage distribution is still favourable. These data vindicate the policies of continuing to offer screening to those who fail to participate and continuing to offer biennial screening to those who have accepted previous offers.

Effect of gender, age and deprivation on key performance indicators in a FOBT-based colorectal screening programme.

OBJECTIVES: To assess the effect of gender, age and deprivation on key performance indicators in a colorectal cancer screening programme. SETTING: Between March 2000 and May 2006 a demonstration pilot of biennial guaiac faecal occult blood test (gFOBT) colorectal screening was carried out in North-East Scotland for all individuals aged 50-69 years. METHODS: The relevant populations were subdivided, by gender, into four age groups and into five deprivation categories according to the Scottish Index of Multiple Deprivation (SIMD), and key performance indicators analysed within these groups. RESULTS: In all rounds, uptake of the gFOBT increased with age (P < 0.001), decreased with increasing deprivation in both genders (P < 0.001), and was consistently higher in women than in men in all age and all SIMD groups. In addition, increasing deprivation was negatively associated with uptake of colonoscopy in men with a positive gFOBT (P < 0.001) although this effect was not observed in women. Positivity rates increased with age (P < 0.001) and increasing deprivation (P < 0.001) in both genders in all rounds, although they were higher in men than in women for all age and SIMD categories. Cancer detection rates increased with age (P < 0.001), were higher in men than in women in all age and SIMD categories, but were not consistently related to deprivation. In both genders, the positive predictive value (PPV) for cancer increased with age (P < 0.001) and decreased with increasing deprivation (P < 0.001) in all rounds and was consistently higher in men than in women in all age and SIMD categories. CONCLUSIONS: In this population-based colorectal screening programme gender, age, and deprivation had marked effects on key performance indicators, and this has implications both for the evaluation of screening programmes and for strategies designed to reduce inequalities.

Results from the first three rounds of the Scottish demonstration pilot of FOBT screening for colorectal cancer.

OBJECTIVES: To assess the effects of the first three rounds of a pilot colorectal screening programme based on guaiac faecal occult blood testing (gFOBT) and their implications for a national population-based programme. METHODS: A demonstration pilot programme was conducted in three Scottish NHS Boards. Residents aged between 50 and 69 years registered on the Community Health Index were included in the study. RESULTS: In the first round, the uptake was 55.0%, the positivity rate was 2.07% and the cancer detection rate was 2.1/1000 screened. In the second round, these were 53.0%, 1.90% and 1.2/1000, respectively, and in the third round, 55.3%, 1.16% and 0.7/1000, respectively. In the first round, the positive predictive value of the gFOBT was 12.0% for cancer and 36.5% for adenoma; these fell to 7.0% and 30.3% in the second round and were maintained at 7.5% and 29.1% in the third round. The percentage of screen-detected cancers diagnosed at Dukes' stage A was 49.2% in the first round, 40.1% in the second round and 36.3% in the third round. CONCLUSIONS: These results are compatible with those of previous randomised trials done in research settings, demonstrating that population-based colorectal cancer screening is feasible in Scotland and should lead to a comparable reduction in disease-specific mortality.

No difference in the association between birth weight and total cholesterol for males and females. A SHARP (Scottish Heart and Arterial Disease Risk Prevention) study.

We carried out a cohort study in a relatively young healthy working population to assess any difference between males and females in the association between birth weight and adult total cholesterol. Perinatal data came from the Walker database of babies born between 1952 and 1966 in Dundee, Scotland. This was record-linked to information from the SHARP (Scottish Heart and Arterial Risk Prevention) cohort who had undergone a cardiovascular risk screening between 1991 and 1993. There were 1158 individuals (56% male, mean age 32.1 years). For both males and females there was no association between birth weight and cholesterol either unadjusted or after adjustment for BMI and other potential confounders: B = -0.11 (95% CI -0.03, 0.04) for males, B = -0.15 (95% CI -0.31, 0.01) for females. All individuals together showed a slight decrease in cholesterol for 1 kg increase in birth weight but only after adjustment for BMI: B = -0.13 (95% CI -0.24, -0.01). These results suggest no difference in the relationship between birth weight and total cholesterol for males and females.

Pre-eclampsia and the later development of type 2 diabetes in mothers and their children: an intergenerational study from the Walker cohort.

AIMS/HYPOTHESIS: Studies have shown a relationship between pre-eclampsia and later coronary artery disease. This study investigated whether there is a relationship between pre-eclampsia and the development of type 2 diabetes in mothers and their babies and how this is affected by infant birthweight. SUBJECTS AND METHODS: This was an intergenerational cohort study. The study population comprised 7,187 mothers who gave birth and 8,648 babies who were born in Dundee, Scotland between 1952 and 1958. Their later diabetic status was defined from 1980 to 2003 by linkage to population-based datasets. RESULTS: There were 810 (11.3%) mothers with pre-eclampsia and 745 (10.4%) who subsequently developed type 2 diabetes. Logistic regression showed an increased risk of developing type 2 diabetes for mothers with pre-eclampsia, unadjusted odds ratio (OR) 1.37 (95% CI 1.10-1.71), p=0.005. This relationship persisted after adjustment for infant birthweight, OR 1.40 (95% CI 1.12-1.75), p=0.003. Of the babies born between 1952 and 1958, 221 (2.6%) had developed type 2 diabetes, 137 of them male (2.9% of male subjects in study population) and 84 female (2.2% of female subjects). The relationship between pre-eclampsia in the mother and the risk of type 2 diabetes in the offspring did not reach statistical significance, OR 1.38 (95% CI 0.90-2.10). Babies with birthweight in the lowest quintile (adjusted for sex, gestation and birth order) had an increased risk of developing type 2 diabetes, OR for lowest quintile vs highest quintile 1.84 (95% CI 1.24-2.72), p=0.002. CONCLUSIONS/INTERPRETATION: Pre-eclampsia is associated with increased risk of developing type 2 diabetes in the mother, but birthweight is a more important determinant of future risk for the offspring.

Whole-cell-reporter-gene-based biosensing systems on a compact disk microfluidics platform.

Biosensing systems such as reporter-gene-based whole-cell assays are increasingly finding applications in biological and environmental screening. A whole-cell approach to such analyses can provide valuable information about the bioavailable level of a compound of interest. These biosensing systems rely on the molecular recognition of a specific analyte by a regulatory protein and, therefore, can detect low levels of the target analyte. In this study, Escherichia coli cells containing plasmid pSD10 were engineered to sense the model target analytes arsenite and antimonite, the target analytes in this study. The biosensing system takes advantage of the recognition of the regulatory protein, ArsR, for arsenite and antimonite to produce the reporter protein, which in this case is GFPuv. The fluorescence emitted by the GFPuv in the cells can be directly related to the concentration of the analyte in the cell, making this biosensing system useful in the detection of arsenite and/or antimonite in a variety of samples. Miniaturization of biosensing systems can further enhance their utility by decreasing reagent consumption and analysis time and by allowing for the high-throughput screening of samples. To that end, we employed a microcentrifugal microfluidics platform that has low power, space, and reagent requirements, increased speed of detection, and the potential for portability. Herein, we demonstrate for the first time the adaptation of a whole-cell sensing system to a microcentrifugal microfluidics platform. Moreover, we were able to detect our target analytes in a rapid and sensitive manner compared to conventional sensing methods.

Magnetoelastic transducers for monitoring coagulation, clot inhibition, and fibrinolysis.

Magnetoelastic transduction has been used to detect and monitor the viscosity changes that occur during the biological reactions of coagulation and fibrinolysis. Magnetoelastic sensors can be used, because the characteristic resonance frequency of the magnetoelastic strip shifts in response to the changes in fluid viscosity. At a set frequency, the output signal can be obtained over time to develop a coagulation and/or dissolution profile, which display the change in viscosity of a plasma sample that has undergone either coagulation or fibrinolysis. For coagulation screening, an exogenous tissue factor is added to an anticoagulated plasma sample to initiate coagulation. Further studies were performed to investigate fibrinolysis through the addition of plasmin. Plasmin is used in two different ways-as a competitive inhibitor before the initiation of clotting and also as a protease to dissolve the previously formed clot. This method is a viable option for the monitoring of processes that are paramount to maintaining hemostasis.

Investigation into the applicability of the centrifugal microfluidics platform for the development of protein-ligand binding assays incorporating enhanced green fluorescent protein as a fluorescent reporter.

The incorporation of a protein-ligand binding assay into a centrifugal microfluidics platform is described. The platform itself is a disc-shaped polymer substrate, upon which a series of microfluidic channels and reservoirs have been machined. Centrifugal microfluidics platforms require no internal moving parts, and fluid propulsion is achieved solely through rotation of the disc. Fluid flow is controlled by passive valves, the opening of which is dependent on the angular frequency of the rotating platform, the channel dimensions, and the physical properties of the fluid. To evaluate the effectiveness of incorporating a protein-based assay onto the centrifugal microfluidics analytical platform, a class-selective, homogeneous assay for the detection of phenothiazine antidepressants was employed. This class of drugs is known to bind to calmodulin, a calcium binding protein. Specifically, a fusion protein between calmodulin and enhanced green fluorescent protein was utilized. Calmodulin undergoes a conformational change upon binding to phenothiazines that alters the fluorescence properties of the attached fluorescent protein, which can be correlated to the concentration of the drug present. Another important aspect of this work was to study the efficacy of the platform to perform reconstitution assays. To do this, the biological reagent was dried on the platform and rehydrated to carry out the assay. The ability to prealiquot reagents on the platform should enhance its versatility and portability. The integration of protein-based assays in this platform should be useful in the design of analytical systems for high-throughput screening of pharmaceuticals and clinical diagnostics.

Review article: The rationale for antidepressant therapy in functional gastrointestinal disorders.

The rationale for antidepressants in the treatment of functional gastrointestinal disorders (FGDs) has been the subject of much interest. However, because of our incomplete understanding of FGDs, this rationale remains unclear. A key point is whether the high degree of psychiatric co-morbidity associated with FGDs (40-90%) represents a shared pathophysiology or the ascertainment bias of tertiary referral patients. Our aims were four-fold: (i) to review the current rationale for antidepressant therapy in FGDs; (ii) to review the studies comparing the characteristics of FGDs with both organic gastrointestinal disease and psychiatric disorders; (iii) to propose a model of FGDs which explains the high psychiatric co-morbidity; (iv) to compare the treatment regimes and effectiveness of antidepressants in FGDs and psychiatric illnesses. The review highlights two important observations. Firstly, the characteristics of FGDs are similar to those of affective disorders and dissimilar to those of organic disease. Secondly, although antidepressants benefit FGD sufferers, their benefits in psychiatric illnesses are greater. We conclude that, in view of the degree of similarity between FGDs and affective disorders, FGDs could be considered as affective disorders in their own right and, if the prescription of antidepressants conformed to their use in affective disorders, FGD morbidity would be reduced.