Small bowel obstruction caused by a fibrotic bow-string appendix: a consequence of non-operative management of acute appendicitis.

A 73-year-old woman presented with small bowel obstruction that failed to settle with conservative management. Over the previous 2 years she had presented twice with computed tomography scan-proven acute appendicitis with localised perforation of the appendix tip. In view of medical comorbidities, she was treated non-operatively with clinical and radiological resolution on each occasion, but on the third presentation laparoscopy was undertaken for non-resolving small bowel obstruction and the non-inflamed appendix itself was identified as a fibrous band causing compression of the distal ileum and complete small bowel obstruction. Following division and appendicectomy, the patient made an uneventful recovery. This case illustrates the potential consequence of repeated appendiceal inflammation and non-operative management and may be seen increasingly as this approach is widely adopted during the COVID-19 pandemic.

Exposure to pH 3.5 water has no effect on the gills of the Amazonian tambaqui (Colossoma macropomum).

Tambaqui (Colossoma macropomum) are a model species for tropical fish physiology, but details are lacking about their ionoregulatory response to acid waters. To provide specifics, we measured unidirectional Na+ fluxes in low pH waters. Sodium influx ([Formula: see text]) was uninhibited during acute exposure to pH 4.5 and 3.5, and Na efflux ([Formula: see text]) rose only slightly at pH 3.5; net Na+ flux ([Formula: see text]) remained positive at all pH. Similarly, during 24 h transfer to pH 3.5 [Formula: see text], [Formula: see text], and [Formula: see text] were unchanged at all times. Taking a closer look at the mechanism of Na+ transport in the gills of tambaqui we found that [Formula: see text] was uninhibited by HMA, a Na+/H+-exchanger blocker, and Benzamil, a Na+-channel inhibitor, casting doubt on their role in Na+ uptake in this fish. Measurement of Na+/K+-ATPase (NKA) and H+-ATPase (VHA) activity showed that neither changed at low pH compared to measurements at pH 6.5. Western blot analysis of ATPase expression saw no changes in amount of NKA and VHA at low pH, and immunohistochemistry showed expression of both NKA and VHA on lamellae and interlamellar region of tambaqui gills and that both proteins co-localized to the same gill cells. Location of expression also did not change in low pH water. Amazingly, tambaqui seem unaffected by pH 3.5 water, making them one of the most acid-tolerant fish species examined so far. In addition, they appear to share key ionoregulatory traits with other fish of the order Characiformes, which suggest a common origin for the ionoregulatory attributes.

Long-term outcomes of real world 'watch and wait' data for rectal cancer after neoadjuvant chemoradiotherapy.

AIM: A 'watch and wait' (W&W) strategy after neoadjuvant long-course chemoradiotherapy (NACRT) remains controversial. Whilst encouraging short-term data exist, the strategy will be judged on long-term data. We present long-term, real-world UK data from a single National Health Service trust. METHODS: An analysis was performed of a prospectively maintained W&W database over 9 years between 2010 and 2018. Outcome measures include incidence and time to regrowth and overall and disease-free survival. RESULTS: We diagnosed 563 rectal cancers in 9 years. In all, 283 patients underwent rectal resection (50.3%). NACRT was used in 155 patients for margin-threatened tumours on staging MRI. Forty-nine patients (31.6%) experienced either a 'near complete' or a complete clinical response (cCR) at their 10 weeks post-NACRT assessment (MRI and endoscopy). The median age was 69 years (range 44-83), and the male to female ratio was 32:17. The median follow-up was 38 months (range 12-96). The median tumour distance from the anal verge was 7 cm (1-15 cm). Twenty-two patients had a cCR on initial assessment and 27 patients had a 'near' cCR. Of those 27 who experienced a 'near' cCR, 17 (63%) progressed to cCR on repeat assessment and 10 (37%) did not. Of these 10 patients, seven underwent standard surgical resection and three were unfit for surgery. R0 for the seven with delayed resection was 100%. Of 39 patients (22 cCR and 17 'near' cCR who progressed to cCR) (25.2% of those receiving NACRT), six patients experienced local regrowth (15.4%). The median time to local regrowth was 29 months (15-60 months). One of these six patients underwent salvage abdominoperineal resection, one was advised to have contact radiotherapy and four opted against surgery and also had contact radiotherapy. The overall survival was 100% at 2 years and 90% at 5 years. Disease-free survival was 90.47% at 2 years and 74.8% at 5 years. CONCLUSION: A W&W treatment strategy was employed safely in this patient cohort with acceptable rates of local regrowth and survival.

The temporal dynamics of humoral immunity to Rickettsia typhi infection in murine typhus patients.

OBJECTIVES: This study examined individuals with Rickettsia typhi infection in the Lao People's Democratic Republic (Lao PDR) to (a) investigate humoral immune dynamics; (b) determine the differences in reference diagnostic results and recommend appropriate cut-offs; (c) determine differences in immune response after different antibiotic treatments; and (d) determine appropriate diagnostic cut-off parameters for indirect immunofluorescence assay (IFA). METHODS: Sequential serum samples from 90 non-pregnant, adults were collected at seven time-points (days 0, 7, 14, 28, 90, 180 and 365) as part of a clinical antibiotic treatment trial. Samples were tested using IFA to determine IgM and IgG antibody reciprocal end-point titres against R. typhi and PCR. RESULTS: For all 90 individuals, reciprocal R. typhi IgM and IgG antibody titres ranged from <400 to ≥3200. The median half-life of R. typhi IgM was 126 days (interquartile range 36-204 days) and IgG was 177 days (interquartile range 134-355 days). Overall median patient titres for R. typhi IgM and IgG were significantly different (p < 0.0001) and at each temporal sample collection point (range p < 0.0001 to p 0.0411). Using Bayesian latent class model analysis, the optimal diagnostic cut-off reciprocal IFA titer on patient admission for IgM was 800 (78.6%, 95% CI 71.6%-85.2% sensitivity; 89.9%, 95% CI 62.5%-100% specificity), and for IFA IgG 1600 (77.3%; 95% CI 68.2%-87.6% sensitivity; 99%, 95% CI 95%-100% specificity). CONCLUSIONS: This study suggests suitable diagnostic cut-offs for local diagnostic laboratories and other endemic settings and highlights antibody persistence following acute infection. Further studies are required to validate and define cut-offs in other geographically diverse locations.

Longitudinal profiling of plasma cytokines in melioidosis and their association with mortality: a prospective cohort study.

OBJECTIVES: To characterize plasma cytokine responses in melioidosis and analyse their association with mortality. METHODS: A prospective longitudinal study was conducted in two hospitals in Northeast Thailand to enrol 161 individuals with melioidosis, plus 13 uninfected healthy individuals and 11 uninfected individuals with diabetes to act as controls. Blood was obtained from all individuals at enrolment (day 0), and at days 5, 12 and 28 from surviving melioidosis patients. Interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, and tumour necrosis factor-α (TNF-α) were assayed in plasma. The association of each cytokine and its dynamics with 28-day mortality was determined. RESULTS: Of the individuals with melioidosis, 131/161 (81%) were bacteraemic, and 68/161 (42%) died. On enrolment, median levels of IFN-γ, IL-6, IL-8, IL-10, IL-23 and TNF-α were higher in individuals with melioidosis compared with uninfected healthy individuals and all but IFN-γ were positively associated with 28-day mortality. Interleukin-8 provided the best discrimination of mortality (area under the receiver operating characteristic curve 0.78, 95% CI 0.71-0.85). Over time, non-survivors had increasing IL-6, IL-8 and IL-17A levels, in contrast to survivors. In joint modelling, temporal trajectories of IFN-γ, IL-6, IL-8, IL-10 and TNF-α predicted survival. CONCLUSIONS: In a severely ill cohort of individuals with melioidosis, specific pro- and anti-inflammatory and T helper type 17 cytokines were associated with survival from melioidosis, at enrolment and over time. Persistent inflammation preceded death. These findings support further evaluation of these mediators as prognostic biomarkers and to guide targeted immunotherapeutic development for severe melioidosis.

Antimicrobial-resistant Gram-negative colonization in infants from a neonatal intensive care unit in Thailand.

Antimicrobial-resistant Gram-negative bacteria are a major cause of morbidity and mortality in hospitalized neonates in South and South-East Asia. This study aimed to determine the dynamics of colonization with antimicrobial-resistant Gram-negative bacteria amongst patients in a neonatal intensive care unit (NICU) in Thailand. From 97 enrolled patients, 52% were colonized by an extended-spectrum ß-lactamase (ESBL) organism at some point during their stay and 64% were colonized by a carbapenem-resistant organism. Rapid acquisition of ESBL-positive and carbapenem-resistant organisms was found. Once colonized with an antibiotic-resistant organism, patients remained colonized for the remainder of their NICU stay.

Epidemiology of paediatric gastrointestinal colonisation by extended spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates in north-west Cambodia.

BACKGROUND: Extended-spectrum cephalosporin resistance (ESC-R) in Escherichia coli and Klebsiella pneumoniae is a healthcare threat; high gastrointestinal carriage rates are reported from South-east Asia. Colonisation prevalence data in Cambodia are lacking. The aim of this study was to determine gastrointestinal colonisation prevalence of ESC-resistant E. coli (ESC-R-EC) and K. pneumoniae (ESC-R-KP) in Cambodian children/adolescents and associated socio-demographic risk factors; and to characterise relevant resistance genes, their genetic contexts, and the genetic relatedness of ESC-R strains using whole genome sequencing (WGS). RESULTS: Faeces and questionnaire data were obtained from individuals < 16 years in north-western Cambodia, 2012. WGS of cultured ESC-R-EC/KP was performed (Illumina). Maximum likelihood phylogenies were used to characterise relatedness of isolates; ESC-R-associated resistance genes and their genetic contexts were identified from de novo assemblies using BLASTn and automated/manual annotation. 82/148 (55%) of children/adolescents were ESC-R-EC/KP colonised; 12/148 (8%) were co-colonised with both species. Independent risk factors for colonisation were hospitalisation (OR: 3.12, 95% CI [1.52-6.38]) and intestinal parasites (OR: 3.11 [1.29-7.51]); school attendance conferred decreased risk (OR: 0.44 [0.21-0.92]. ESC-R strains were diverse; the commonest ESC-R mechanisms were blaCTX-M 1 and 9 sub-family variants. Structures flanking these genes were highly variable, and for blaCTX-M-15, - 55 and - 27 frequently involved IS26. Chromosomal blaCTX-M integration was common in E. coli. CONCLUSIONS: Gastrointestinal ESC-R-EC/KP colonisation is widespread in Cambodian children/adolescents; hospital admission and intestinal parasites are independent risk factors. The genetic contexts of blaCTX-M are highly mosaic, consistent with rapid horizontal exchange. Chromosomal integration of blaCTX-M may result in stable propagation in these community-associated pathogens.

Toxigenic Clostridium difficile carriage in general practice: results of a laboratory-based cohort study.

OBJECTIVES: Reported rates of community-acquired Clostridium difficile infections (CDIs) have been increasing. However, the true burden of the disease in general practice is unknown in France. Our objective was to determine the incidence of toxigenic C. difficile carriage and the percentage of stool samples prescribed by general practitioners (GPs) which contained free C. difficile toxins. METHODS: During an 11-month period, all stool samples submitted for any enteric pathogen detection to 15 different private laboratories in Paris and the surrounding areas were tested for C. difficile, irrespective of the GPs' request. A clinical questionnaire was completed for each patient. Stool samples were screened using a rapid simultaneous glutamate dehydrogenase and toxins A/B detection test: any positive result (glutamate dehydrogenase or toxin) was further confirmed by the stool cytotoxicity assay (CTA) on MRC-5 cells and by toxigenic culture (TC) at a central laboratory. The C. difficile isolates were characterized by PCR ribotyping. RESULTS: A total of 2541 patients (1295 female, 1246 male) were included. The incidences of patients with a positive toxigenic culture and a positive CTA were 3.27% (95% CI 2.61%-4.03%) and 1.81% (95% CI 1.33%-2.41%), respectively. GPs requested C. difficile testing in only 12.93% of the stool samples, detecting 52.30% of all TC-positive patients. The 83 toxigenic C. difficile strains belonged to 36 different PCR ribotypes. CONCLUSIONS: Toxigenic C. difficile carriage is frequent in general practice but remains under-recognized. It may affect young patients without previous antimicrobial therapy or hospitalization.

Cost-effectiveness of interventions to improve hand hygiene in healthcare workers in middle-income hospital settings: a model-based analysis.

BACKGROUND: Multi-modal interventions are effective in increasing hand hygiene (HH) compliance among healthcare workers, but it is not known whether such interventions are cost-effective outside high-income countries. AIM: To evaluate the cost-effectiveness of multi-modal hospital interventions to improve HH compliance in a middle-income country. METHODS: Using a conservative approach, a model was developed to determine whether reductions in meticillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSIs) alone would make HH interventions cost-effective in intensive care units (ICUs). Transmission dynamic and decision analytic models were combined to determine the expected impact of HH interventions on MRSA-BSI incidence and evaluate their cost-effectiveness. A series of sensitivity analyses and hypothetical scenarios making different assumptions about transmissibility were explored to generalize the findings. FINDINGS: Interventions increasing HH compliance from a 10% baseline to ≥20% are likely to be cost-effective solely through reduced MRSA-BSI. Increasing compliance from 10% to 40% was estimated to cost US$2515 per 10,000 bed-days with 3.8 quality-adjusted life-years (QALYs) gained in a paediatric ICU (PICU) and US$1743 per 10,000 bed-days with 3.7 QALYs gained in an adult ICU. If baseline compliance is not >20%, the intervention is always cost-effective even with only a 10% compliance improvement. CONCLUSION: Effective multi-modal HH interventions are likely to be cost-effective due to preventing MRSA-BSI alone in ICU settings in middle-income countries where baseline compliance is typically low. Where compliance is higher, the cost-effectiveness of interventions to improve it further will depend on the impact on hospital-acquired infections other than MRSA-BSI.

Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria; a randomized comparison of artesunate and quinine.

BACKGROUND: Parenteral artesunate is the treatment of choice for severe malaria. Recently, haemolytic anaemia occurring 1 to 3 weeks after artesunate treatment of falciparum malaria has been reported in returning travellers in temperate countries. METHODS: To assess these potential safety concerns in African children, in whom most deaths from malaria occur, an open-labelled, randomized controlled trial was conducted in Kinshasa, Democratic Republic of Congo. 217 children aged between 6 months and 14 years with acute uncomplicated falciparum malaria and parasite densities over 100,000/µL were randomly allocated to intravenous artesunate or quinine, hospitalized for 3 days and then followed for 42 days. RESULTS: The immediate reduction in haemoglobin was less with artesunate than with quinine: median (IQR) fall at 72 h 1.4 g/dL (0.90-1.95) vs. 1.7 g/dL (1.10-2.40) (p = 0.009). This was explained by greater pitting then recirculation of once infected erythrocytes. Only 5% of patients (in both groups) had a ≥ 10% reduction in haemoglobin after day 7 (p = 0.1). One artesunate treated patient with suspected concomitant sepsis had a protracted clinical course and required a blood transfusion on day 14. CONCLUSIONS: Clinically significant delayed haemolysis following parenteral artesunate is uncommon in African children hospitalised with acute falciparum malaria and high parasitaemias. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT02092766 (18/03/2014).

Preoperative Prediction of Node-Negative Disease After Neoadjuvant Chemotherapy in Patients Presenting with Node-Negative or Node-Positive Breast Cancer.

BACKGROUND: Axillary node status after neoadjuvant chemotherapy (NAC) influences the axillary surgical staging procedure as well as recommendations regarding reconstruction and radiation. OBJECTIVE: Our aim was to construct a clinical preoperative prediction model to identify the likelihood of patients being node negative after NAC. METHODS: Using the National Cancer Database (NCDB) from January 2010 to December 2012, we identified cT1-T4c, N0-N3 breast cancer patients treated with NAC. The effects of patient and tumor factors on pathologic node status were assessed by multivariable logistic regression separately for clinically node negative (cN0) and clinically node positive (cN+) disease, and two models were constructed. Model performance was validated in a cohort of NAC patients treated at our institution (January 2013-July 2016), and model discrimination was assessed by estimating the area under the curve (AUC). RESULTS: Of 16,153 NCDB patients, 6659 (41%) were cN0 and 9494 (59%) were cN+. Factors associated with pathologic nodal status and included in the models were patient age, tumor grade, biologic subtype, histology, clinical tumor category, and, in cN+ patients only, clinical nodal category. The validation dataset included 194 cN0 and 180 cN+ patients. The cN0 model demonstrated good discrimination, with an AUC of 0.73 (95% confidence interval [CI] 0.72-0.74) in the NCDB and 0.77 (95% CI 0.68-0.85) in the external validation, while the cN+ patient model AUC was 0.71 (95% CI 0.70-0.72) in the NCDB and 0.74 (95% CI 0.67-0.82) in the external validation. CONCLUSIONS: We constructed two models that showed good discrimination for predicting ypN0 status following NAC in cN0 and cN+ patients. These clinically useful models can guide surgical planning after NAC.

Mice with Dab1 or Vldlr insufficiency exhibit abnormal neonatal vocalization patterns.

Genetic and epigenetic changes in components of the Reelin-signaling pathway (RELN, DAB1) are associated with autism spectrum disorder (ASD) risk. Social communication deficits are a key component of the ASD diagnostic criteria, but the underlying neurogenetic mechanisms remain unknown. Reln insufficient mice exhibit ASD-like behavioral phenotypes including altered neonatal vocalization patterns. Reelin affects multiple pathways including through the receptors, Very low-density lipoprotein receptor (Vldlr), Apolipoprotein receptor 2 (Apoer2), and intracellular signaling molecule Disabled-1 (Dab1). As Vldlr was previously implicated in avian vocalization, here we investigate vocalizations of neonatal mice with a reduction or absence of these components of the Reelin-signaling pathway. Mice with low or no Dab1 expression exhibited reduced calling rates, altered call-type usage, and differential vocal development trajectories. Mice lacking Vldlr expression also had altered call repertoires, and this effect was exacerbated by deficiency in Apoer2. Together with previous findings, these observations 1) solidify a role for Reelin in vocal communication of multiple species, 2) point to the canonical Reelin-signaling pathway as critical for development of normal neonatal calling patterns in mice, and 3) suggest that mutants in this pathway could be used as murine models for Reelin-associated vocal deficits in humans.

Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10.

OBJECTIVE: To assess offspring attention-deficit hyperactivity disorder (ADHD) symptoms and emotional/behavioural impairments at age 10 years in relation to maternal gestational weight gain (GWG) and prepregnancy body mass index (BMI). DESIGN AND SETTING: Longitudinal birth cohort from Magee-Womens Hospital, Pittsburgh, Pennsylvania (enrolled 1983-86). POPULATION: Mother-infant dyads (n = 511) were followed through pregnancy to 10 years. METHODS: Self-reported total GWG was converted to gestational-age-standardised z-scores. Multivariable linear and negative binomial regressions were used to estimate effects of GWG and BMI on outcomes. MAIN OUTCOME MEASURES: Child ADHD symptoms were assessed with the Conners' Continuous Performance Test. Child behaviour was assessed by parent and teacher ratings on the Child Behaviour Checklist (CBCL) and Teacher Report Form, respectively. RESULTS: The mean (SD) total GWG (kg) was 14.5 (5.9), and 10% of women had a pregravid BMI ≥30 kg/m2 . Prepregnancy obesity (BMI of 30 kg/m2 ) was associated with increased offspring problem behaviours including internalising behaviours (adjusted ß 3.3 points, 95% CI 1.7-4.9), externalising behaviours (adjusted ß 2.9 points, 95% CI 1.4-4.6), and attention problems (adjusted ß 2.3 points, 95% CI 1.1-3.4) on the CBCL, compared with normal weight mothers (BMI of 22 kg/m2 ). There were nonsignificant trends towards increased offspring impulsivity with low GWG among lean mothers (adjusted incidence rate ratio 1.2, 95% CI 0.9-1.5) and high GWG among overweight mothers (adjusted incidence rate ratio 1.7, 95% CI 0.9-2.8), but additional outcomes did not differ by GWG z-score. Results were not meaningfully different after excluding high-substance users. CONCLUSIONS: In a low-income and high-risk sample, we observed a small increase in child behaviour problems among children of obese mothers, which could have an impact on child behaviour in the population. TWEETABLE ABSTRACT: Maternal obesity is associated with a small increase in child behaviour problems.

Gestational weight gain and the risk of offspring obesity at 10 and 16 years: a prospective cohort study in low-income women.

OBJECTIVE: To study the association between gestational weight gain (GWG) and offspring obesity risk at ages chosen to approximate prepuberty (10 years) and postpuberty (16 years). DESIGN: Prospective pregnancy cohort. SETTING: Pittsburgh, PA, USA. SAMPLE: Low-income pregnant women (n = 514) receiving prenatal care at an obstetric residency clinic and their singleton offspring. METHODS: Gestational weight gain was classified based on maternal GWG-for-gestational-age Z-score charts and was modelled using flexible spline terms in modified multivariable Poisson regression models. MAIN OUTCOME MEASURES: Obesity at 10 or 16 years, defined as body mass index (BMI) Z-scores ≥95th centile of the 2000 CDC references, based on measured height and weight. RESULTS: The prevalence of offspring obesity was 20% at 10 years and 22% at 16 years. In the overall sample, the risk of offspring obesity at 10 and 16 years increased when GWG exceeded a GWG Z-score of 0 SD (equivalent to 30 kg at 40 weeks); but for gains below a Z-score of 0 SD there was no relationship with child obesity risk. The association between GWG and offspring obesity varied by prepregnancy BMI. Among mothers with a pregravid BMI <25 kg/m(2) , the risk of offspring obesity increased when GWG Z-score exceeded 0 SD, yet among overweight women (BMI ≥25 kg/m(2) ), there was no association between GWG Z-scores and offspring obesity risk. CONCLUSIONS: Among lean women, higher GWG may have lasting effects on offspring obesity risk.

Extensive Within-Host Diversity in Fecally Carried Extended-Spectrum-Beta-Lactamase-Producing Escherichia coli Isolates: Implications for Transmission Analyses.

Studies of the transmission epidemiology of antimicrobial-resistant Escherichia coli, such as strains harboring extended-spectrum beta-lactamase (ESBL) genes, frequently use selective culture of rectal surveillance swabs to identify isolates for molecular epidemiological investigation. Typically, only single colonies are evaluated, which risks underestimating species diversity and transmission events. We sequenced the genomes of 16 E. coli colonies from each of eight fecal samples (n = 127 genomes; one failure), taken from different individuals in Cambodia, a region of high ESBL-producing E. coli prevalence. Sequence data were used to characterize both the core chromosomal diversity of E. coli isolates and their resistance/virulence gene content as a proxy measure of accessory genome diversity. The 127 E. coli genomes represented 31 distinct sequence types (STs). Seven (88%) of eight subjects carried ESBL-positive isolates, all containing blaCTX-M variants. Diversity was substantial, with a median of four STs/individual (range, 1 to 10) and wide genetic divergence at the nucleotide level within some STs. In 2/8 (25%) individuals, the same blaCTX-M variant occurred in different clones, and/or different blaCTX-M variants occurred in the same clone. Patterns of other resistance genes and common virulence factors, representing differences in the accessory genome, were also diverse within and between clones. The substantial diversity among intestinally carried ESBL-positive E. coli bacteria suggests that fecal surveillance, particularly if based on single-colony subcultures, will likely underestimate transmission events, especially in high-prevalence settings.

Spatio-temporal patterns of leptospirosis in Thailand: is flooding a risk factor?

We studied the temporal and spatial patterns of leptospirosis, its association with flooding and animal census data in Thailand. Flood data from 2010 to 2012 were extracted from spatial information taken from satellite images. The incidence rate ratio (IRR) was used to determine the relationship between spatio-temporal flooding patterns and the number of human leptospirosis cases. In addition, the area of flood coverage, duration of waterlogging, time lags between flood events, and a number of potential animal reservoirs were considered in a sub-analysis. There was no significant temporal trend of leptospirosis over the study period. Statistical analysis showed an inconsistent relationship between IRR and flooding across years and regions. Spatially, leptospirosis occurred repeatedly and predominantly in northeastern Thailand. Our findings suggest that flooding is less influential in leptospirosis transmission than previously assumed. High incidence of the disease in the northeastern region is explained by the fact that agriculture and animal farming are important economic activities in this area. The periodic rise and fall of reported leptospirosis cases over time might be explained by seasonal exposure from rice farming activities performed during the rainy season when flood events often occur. We conclude that leptospirosis remains an occupational disease in Thailand.

Is gestational weight gain associated with offspring obesity at 36 months?

OBJECTIVE: We examined the association between gestational weight gain (GWG) and offspring obesity at age 36 months. METHODS: Mother-infant dyads (n = 609) were followed from a first study visit (mean [standard deviation]: 18.8 [2.7] weeks gestation) to 36 months postpartum. Total GWG over the entire pregnancy was defined as excessive or non-excessive according to the 2009 Institute of Medicine guidelines. Four mutually exclusive categories of excessive or non-excessive GWG across early (conception to first study visit) and late (first study visit to delivery) pregnancy defined GWG pattern. Body mass index (BMI) z-scores ≥95th percentile of the 2000 Centers for Disease Control (CDC) references defined offspring obesity at 36 months. Multivariable log-binomial models adjusted for pre-pregnancy BMI and breastfeeding were used to estimate the association between GWG and childhood obesity risk. RESULTS: Nearly half of the women had total excessive GWG. Of these, 46% gained excessively during both early and late pregnancy while 22% gained excessively early and non-excessively late, and the remaining 32% gained non-excess weight early and excessively later. Thirteen per cent of all children were obese at 36 months. Excessive total GWG was associated with more than twice the risk of child obesity (adjusted risk ratio [95% confidence interval]: 2.20 [1.35, 3.61]) compared with overall non-excessive GWG. Compared with a pattern of non-excessive GWG in both early and late pregnancy, excessive GWG in both periods was associated with an increased risk of obesity (2.39 [1.13, 5.08]). CONCLUSIONS: Excessive GWG is a potentially modifiable factor that may influence obesity development in early childhood.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults.

BACKGROUND: Studies have demonstrated that an early age of onset of marijuana use (EAOM) is associated with a higher risk of developing psychotic symptoms (PS) compared to initiating marijuana use at a later age or not at all. Research has also found that prenatal marijuana exposure (PME) predicts EAOM. This report evaluates the relationships among PME, EAOM, and PS. METHOD: Subjects were initially interviewed in their fourth prenatal month. Women and offspring who completed the birth assessment (n = 763) were selected for follow-up. Women and their offspring were followed until the offspring were 22 years of age: 596 offspring were evaluated. At age 22, PS were assessed in the offspring with the Diagnostic Interview Schedule using DSM-IV criteria. Analyses controlled for significant covariates including other prenatal substance exposures, race, gender, and offspring substance use at 22 years. RESULTS: PME and EAOM significantly predicted increased rates of PS at 22 years controlling for other significant covariates. The direct effect of PME on PS was marginally significant (p = 0.06) when EAOM was entered into the model and other covariates were fixed. In the mediation analysis, EAOM did not significantly mediate the association between PME and PS, controlling for significant covariates, nor was the indirect pathway significant when structural equation modeling was used. The total effect of the direct and indirect pathways was significant. CONCLUSIONS: In addition to EAOM, PME may also play a role in the association between marijuana use and the development of PS. This could highlight a new area for prevention.

Rectal mucocoele following subtotal colectomy for colitis.

We present a unique case of a rectal mucocoele affecting a patient several years after his subtotal colectomy for ulcerative colitis. This was secondary to both a benign anorectal stenosis and a benign mucus secreting rectal adenoma. This case highlights the importance of surveillance in such patients.

Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand.

Dihydroartemisinin-piperaquine is an effective drug in the treatment of Plasmodium falciparum and P. vivax malaria. The objective of this study was to evaluate the population pharmacokinetics and pharmacodynamics of piperaquine in patients with P. vivax malaria in Thailand after a standard regimen of dihydroartemisinin-piperaquine to determine whether residual piperaquine prevents or delays the emergence of P. vivax relapse. Sparse blood samples were collected from 116 patients. Piperaquine pharmacokinetics were described well by a three-compartment distribution model. Relapsing P. vivax malaria was accommodated by a constant baseline hazard (8.94 relapses/year) with the addition of a surge function in a fixed 3-week interval and a protective piperaquine effect. The results suggest that a large proportion of the first relapses were suppressed completely by residual piperaquine concentrations and that recurrences resulted mainly from emergence of the second or third relapse or from reinfection. This suggests a significant reduction in P. vivax morbidity when using dihydroartemisinin-piperaquine compared with other antimalarial drugs with shorter terminal postprophylactic effects.