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Pharmacoepidemiological studies provide important information on the safety and effectiveness of medications, but the validity of study findings can be threatened by residual bias. Ideally, biases would be minimized through appropriate study design and statistical analysis methods. However, residual biases can remain, for example, due to unmeasured confounders, measurement error, or selection into the study. A group of sensitivity analysis methods, termed quantitative bias analyses, are available to assess, quantitatively and transparently, the robustness of study results to these residual biases. These approaches include methods to quantify how the estimated effect would be altered under specified assumptions about the potential bias, and methods to calculate bounds on effect estimates. This article introduces quantitative bias analyses for unmeasured confounding, misclassification, and selection bias, with a focus on their relevance and application to pharmacoepidemiological studies. [ABSTRACT FROM AUTHOR]

Purpose: There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic. Methods: We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022. Data were extracted on the frequency and types of programming code shared, and other key open science practices (clinical codelist sharing, data sharing, study preregistration, and stated use of reporting guidelines and preprinting). We developed six recommendations for investigators who choose to share code and gathered feedback from members of the International Society for Pharmacoepidemiology (ISPE). Results: Programming code sharing by articles published in PDS ranged from 1.8% in 2017 to 9.5% in 2022. It was more prevalent among articles with a methodological focus, simulation studies, and papers which also shared record‐level data. Conclusion: Programming code sharing is rare but increasing in pharmacoepidemiology studies published in PDS. We recommend improved reporting of whether code is shared and how available code can be accessed. When sharing programming code, we recommend the use of permanent digital identifiers, appropriate licenses, and, where possible, adherence to good software practices around the provision of metadata and documentation, computational reproducibility, and data privacy. [ABSTRACT FROM AUTHOR]

Purpose: Prevalent new user (PNU) designs extend the active comparator new user design by allowing for the inclusion of initiators of the study drug who were previously on a comparator treatment. We performed a literature review summarising current practice. Methods: PubMed was searched for studies applying the PNU design since its proposal in 2017. The review focused on three components. First, we extracted information on the overall study design, including the database used. We summarised information on implementation of the PNU design, including key decisions relating to exposure set definition and estimation of time‐conditional propensity scores. Finally, we reviewed the analysis strategy of the matched cohort. Results: Nineteen studies met the criteria for inclusion. Most studies (73%) implemented the PNU design in electronic health record or registry databases, with the remaining using insurance claims databases. Of 15 studies including a class of prevalent users, 40% deviated from the original exposure set definition proposals in favour of a more complex definition. Four studies did not include prevalent new users but used other aspects of the PNU framework. Several studies lacked details on exposure set definition (n = 2), time‐conditional propensity score model (n = 2) or integration of complex analytical techniques, such as the high‐dimensional propensity score algorithm (n = 3). Conclusion: PNU designs have been applied in a range of therapeutic and disease areas. However, to encourage more widespread use of this design and help shape best practice, there is a need for improved accessibility, specifically through the provision of analytical code alongside guidance to support implementation and transparent reporting. [ABSTRACT FROM AUTHOR]

Aims: To assess any disparities in the initiation of second‐line antidiabetic treatments prescribed among people with type 2 diabetes mellitus (T2DM) in England according to ethnicity and social deprivation level. Materials and methods: This cross‐sectional study used linked primary (Clinical Practice Research Datalink) and secondary care data (Hospital Episode Statistics), and the Index of Multiple Deprivation (IMD). We included people aged 18 years or older with T2DM who intensified to second‐line oral antidiabetic medication between 2014 and 2020 to investigate disparities in second‐line antidiabetic treatment prescribing (one of sulphonylureas [SUs], dipeptidyl peptidase‐4 [DPP‐4] inhibitors, or sodium‐glucose cotransporter‐2 [SGLT2] inhibitors, in combination with metformin) by ethnicity (White, South Asian, Black, mixed/other) and deprivation level (IMD quintiles). We report prescriptions of the alternative treatments by ethnicity and deprivation level according to predicted percentages derived from multivariable, multinomial logistic regression. Results: Among 36 023 people, 85% were White, 10% South Asian, 4% Black and 1% mixed/other. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by ethnicity were 21% (95% confidence interval [CI] 19–23%), 20% (95% CI 18–22%), 19% (95% CI 16–22%) and 17% (95% CI 14–21%) among people with White, South Asian, Black, and mixed/other ethnicity, respectively. After adjustment, the predicted percentages for SGLT2 inhibitor prescribing by deprivation were 22% (95% CI 20–25%) and 19% (95% CI 17–21%) for the least deprived and the most deprived quintile, respectively. When stratifying by prevalent cardiovascular disease (CVD) status, we found lower predicted percentages of people with prevalent CVD prescribed SGLT2 inhibitors compared with people without prevalent CVD across all ethnicity groups and all levels of social deprivation. Conclusions: Among people with T2DM, there were no substantial differences by ethnicity or deprivation level in the percentage prescribed either SGLT2 inhibitors, DPP‐4 inhibitors or SUs as second‐line antidiabetic treatment. [ABSTRACT FROM AUTHOR]

Purpose: Signal detection is a crucial step in the discovery of post‐marketing adverse drug reactions. There is a growing interest in using routinely collected data to complement established spontaneous report analyses. This work aims to systematically review the methods for drug safety signal detection using routinely collected healthcare data and their performance, both in general and for specific types of drugs and outcomes. Methods: We conducted a systematic review following the PRISMA guidelines, and registered a protocol in PROSPERO. MEDLINE, EMBASE, PubMed, Web of Science, Scopus, and the Cochrane Library were searched until July 13, 2021. Results: The review included 101 articles, among which there were 39 methodological works, 25 performance assessment papers, and 24 observational studies. Methods included adaptations from those used with spontaneous reports, traditional epidemiological designs, methods specific to signal detection with real‐world data. More recently, implementations of machine learning have been studied in the literature. Twenty‐five studies evaluated method performances, 16 of them using the area under the curve (AUC) for a range of positive and negative controls as their main measure. Despite the likelihood that performance measurement could vary by drug‐event pair, only 10 studies reported performance stratified by drugs and outcomes, in a heterogeneous manner. The replicability of the performance assessment results was limited due to lack of transparency in reporting and the lack of a gold standard reference set. Conclusions: A variety of methods have been described in the literature for signal detection with routinely collected data. No method showed superior performance in all papers and across all drugs and outcomes, performance assessment and reporting were heterogeneous. However, there is limited evidence that self‐controlled designs, high dimensional propensity scores, and machine learning can achieve higher performances than other methods. [ABSTRACT FROM AUTHOR]

Purpose The high‐dimensional propensity score (HDPS) is a semi‐automated procedure for confounder identification, prioritisation and adjustment in large healthcare databases that requires investigators to specify data dimensions, prioritisation strategy and tuning parameters. In practice, reporting of these decisions is inconsistent and this can undermine the transparency, and reproducibility of results obtained. We illustrate reporting tools, graphical displays and sensitivity analyses to increase transparency and facilitate evaluation of the robustness of analyses involving HDPS. Methods: Using a study from the UK Clinical Practice Research Datalink that implemented HDPS we demonstrate the application of the proposed recommendations. Results: We identify seven considerations surrounding the implementation of HDPS, such as the identification of data dimensions, method for code prioritisation and number of variables selected. Graphical diagnostic tools include assessing the balance of key confounders before and after adjusting for empirically selected HDPS covariates and the identification of potentially influential covariates. Sensitivity analyses include varying the number of covariates selected and assessing the impact of covariates behaving empirically as instrumental variables. In our example, results were robust to both the number of covariates selected and the inclusion of potentially influential covariates. Furthermore, our HDPS models achieved good balance in key confounders. Conclusions: The data‐adaptive approach of HDPS and the resulting benefits have led to its popularity as a method for confounder adjustment in pharmacoepidemiological studies. Reporting of HDPS analyses in practice may be improved by the considerations and tools proposed here to increase the transparency and reproducibility of study results. [ABSTRACT FROM AUTHOR]

This study investigates the generalizability and predictive validity of associations between gastrointestinal (GI) symptoms and youth anxiety to establish their utility in community mental health decision‐making. We analyzed data from youth ages 3 to 21 years in volunteer cohorts collected in Los Angeles (N = 327) and New York City (N = 102), as well as the Healthy Brain Network cohort (N = 1957). Youth GI distress was measured through items taken from the parent‐reported Child Behavior Checklist (CBCL). We examined generalizability of GI–anxiety associations across cohorts and anxiety reporters, then evaluated the performance of these models in predicting youth anxiety in holdout data. Consistent with previous work, higher levels of gastrointestinal distress were associated with more parent‐reported youth anxiety behaviors in all three cohorts. Models trained on data from the Healthy Brain Network cohort predicted parent‐reported and child‐reported anxiety behaviors, as well as clinician‐evaluated anxiety diagnoses, at above chance levels in holdout data. Models which included GI symptoms often, but not always, outperformed models based on age and sex alone in predicting youth anxiety. Based on the generalizability and predictive validity of GI–anxiety associations investigated here, GI symptoms may be an effective tool for child‐facing professionals for identifying children at risk for anxiety (Preprint: https://psyarxiv.com/zgavu/). [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between proton pump inhibitors (PPIs) and both all‐cause and cause‐specific mortality. Methods: We conducted a cohort study using the UK Clinical Practice Research Datalink GOLD database. We compared 733 885 new users of PPIs to 124 410 new users of H2 receptor antagonists (H2Ras). In a secondary analysis we compared 689 602 PPI new users to 1 361 245 nonusers of acid suppression therapy matched on age, sex and calendar year. Hazard ratios for all‐cause and cause‐specific mortality were estimated using propensity score (PS) weighted Cox models. Results: PPI prescription was associated with increased risk of all‐cause mortality, with hazard ratios decreasing considerably by increasing adjustment (unadjusted hazard ratio [HR] 1.65, 95% confidence interval [CI] 1.62‐1.69; PS‐weighted HR 1.38, 95% CI 1.33‐1.44; high‐dimensional PS‐weighted HR 1.31, 95% CI 1.26‐1.37). Short‐term associations were observed with mortality from causes where a causal short‐term association is unexpected (eg, lung cancer mortality: PS‐weighted HR at 6 months 1.77, 95% CI 1.39‐2.25). Adjusted hazard ratios were substantially higher when compared to nonusers (PS‐weighted HR all‐cause mortality 1.96, 95% CI 1.94‐1.99) rather than H2RA users. Conclusions: PPI prescription was strongly associated with all‐cause and cause‐specific mortality. However, the change in hazard ratios (a) by increasing adjustment and (b) between comparator groups indicates that residual confounding is likely to explain the association between poor health outcomes and PPI use, and fully accounting for this using observational data may not be possible. [ABSTRACT FROM AUTHOR]

Background and aims: Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care. Design Case–cross‐over study. Setting: UK‐based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets. Participants: Adult smokers (n =282,429) observed during periods when exposed and not exposed to either varenicline or NRT. Measurements Main outcomes included suicide, self‐harm, myocardial infarction (MI), all‐cause death and cause‐specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91–180 days prior to the event) or multiple 90‐day reference periods to increase statistical power. Findings In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18–1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self‐harm (OR = 1.32, 95% CI = 1.12–1.56) and suicide (OR = 3.56, 95% CI = 1.32–9.60) but a reduction in all‐cause death (OR = 0.75, 95% CI = 0.61–0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36–1.74), self‐harm (OR = 1.30, 95% CI = 1.18–1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11–2.10), COPD (OR = 1.33, 95% CI = 1.14–1.56) and all causes (OR = 1.28, 95% CI = 1.18–1.40) when using multiple reference periods. Conclusions: There appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self‐harm and (2) varenicline and increased risk of self‐harm and suicide, as well as a negative association between varenicline and all‐cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self‐harm). [ABSTRACT FROM AUTHOR]

Column experiments containing an aquifer sand were subjected to static and oscillating water tables to investigate the impact of natural fluctuations and rainfall infiltration on the groundwater bacterial community just below the phreatic surface, and its association with the geochemistry. Once the columns were established, the continuously saturated zone was anoxic in all three columns. The rate of soil organic matter (SOM) mineralization was higher when the water table varied cyclically than when it was static due to the greater availability of NO3− and SO42−. Natural fluctuations in the water table resulted in a similar NO3− concentration to that observed with a static water table but the cyclic wetting of the intermittently saturated zone resulted in a higher SO42− concentration. Rainfall infiltration induced cyclic water‐table variations resulted in a higher NO3− concentration than those in the other two columns, and a SO42− concentration intermediate between those columns. As rainwater infiltration resulted in slow downward displacement of the groundwater, it is inferred that NO3− and SO42− were being mobilized from the vadose zone. NO3− was mainly released by SOM mineralization (which was enhanced by the infiltration of oxygenated rainwater), but the larger amount of SO42− release required a second mechanism (possibly desorption). Different groundwater bacterial communities evolved from initially similar populations due to the different groundwater histories. [ABSTRACT FROM AUTHOR]

Purpose Recent evidence from US claims data suggests use of high‐dimensional propensity score (hd‐PS) methods improve adjustment for confounding in non‐randomised studies of interventions. However, it is unclear how best to apply hd‐PS principles outside their original setting, given important differences between claims data and electronic health records (EHRs). We aimed to implement the hd‐PS in the setting of United Kingdom (UK) EHRs. Methods: We studied the interaction between clopidogrel and proton pump inhibitors (PPIs). Whilst previous observational studies suggested an interaction (with reduced effect of clopidogrel), case‐only, genetic and randomised trial approaches showed no interaction, strongly suggesting the original observational findings were subject to confounding. We derived a cohort of clopidogrel users from the UK Clinical Practice Research Datalink linked with the Myocardial Ischaemia National Audit Project. Analyses estimated the hazard ratio (HR) for myocardial infarction (MI) comparing PPI users with non‐users using a Cox model adjusting for confounders. To reflect unique characteristics of UK EHRs, we varied the application of hd‐PS principles including the level of grouping within coding systems and adapting the assessment of code recurrence. Results were compared with traditional analyses. Results: Twenty‐four thousand four hundred and seventy‐one patients took clopidogrel, of whom 9111 were prescribed a PPI. Traditional PS approaches obtained a HR for the association between PPI use and MI of 1.17 (95% CI: 1.00‐1.35). Applying hd‐PS modifications resulted in estimates closer to the expected null (HR 1.00; 95% CI: 0.78‐1.28). Conclusions: hd‐PS provided improved adjustment for confounding compared with other approaches, suggesting hd‐PS can be usefully applied in UK EHRs. [ABSTRACT FROM AUTHOR]

Aim: To assess the comparative effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors, sulphonylureas (SUs) and dipeptidyl peptidase‐4 (DPP‐4) inhibitors on cardiometabolic risk factors in routine care. Materials and methods: Using primary care data on 10 631 new users of SUs, SGLT2 inhibitors or DPP‐4 inhibitors added to metformin, obtained from the UK Clinical Practice Research Datalink, we created propensity‐score matched cohorts and used linear mixed models to describe changes in glycated haemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), systolic blood pressure (BP) and body mass index (BMI) over 96 weeks. Results: HbA1c levels fell substantially after treatment intensification for all drugs: mean change at week 12: SGLT2 inhibitors: −15.2 mmol/mol (95% confidence interval [CI] –16.9, −13.5); SUs: −14.3 mmol/mol (95% CI –15.5, −13.2); and DPP‐4 inhibitors: −11.9 mmol/mol (95% CI –13.1, −10.6). Systolic BP fell for SGLT2 inhibitor users throughout follow‐up, but not for DPP‐4 inhibitor or SU users: mean change at week 12: SGLT2 inhibitors: −2.3 mmHg (95% CI –3.8, −0.8); SUs: −0.8 mmHg (95% CI –1.9, +0.4); and DPP‐4 inhibitors: −0.9 mmHg (95% CI –2.1,+0.2). BMI decreased for SGLT2 inhibitor and DPP‐4 inhibitor users, but not SU users: mean change at week 12: SGLT2 inhibitors: −0.7 kg/m2 (95% CI –0.9, −0.5); SUs: 0.0 kg/m2 (95% CI –0.3, +0.2); and DPP‐4 inhibitors: −0.3 kg/m2 (95% CI –0.5, −0.1). eGFR fell at 12 weeks for SGLT2 inhibitor and DPP‐4 inhibitor users. At 60 weeks, the fall in eGFR from baseline was similar for each drug class. Conclusions: In routine care, SGLT2 inhibitors had greater effects on cardiometabolic risk factors than SUs. Routine care data closely replicated the effects of diabetes drugs on physiological variables measured in clinical trials. [ABSTRACT FROM AUTHOR]

Background: In self‐controlled case series (SCCS), the event should not condition the probability of subsequent exposure. If this assumption is not met, an important bias could take place. The association of hip/femur fracture (HFF) and use of benzodiazepines (BDZ) has a bidirectional causal relationship and can serve as case study to investigate the impact of this methodological issue. Objectives: To assess the magnitude of bias introduced in a SCCS when HFF conditions the posterior exposure to BDZ and explore ways to correct it. Methods: Four thousand four hundred fifty cases of HFF who had at least one BZD prescription were selected from the primary care health record database BIFAP. Exposure to BZD was divided into non‐use, current, recent, and past use. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs) of HFF among current vs non‐use/past, adjusted for age. To investigate possible event‐exposure dependence, a pre‐exposure time of different lengths (15, 30, and 60 days) was excluded from the reference category to evaluate the IRR. Results: IRR of HHF for current use was 0.79 (0.72‐0.86); removing 30 days, IRR was 1.43 (1.31‐1.57). Removing 15 days, IRR was 1.29 (1.18‐1.41), and removing 60 days, IRR was 1.56 (1.42‐1.72). A pre‐exposure period up to 182 days was necessary to remove such effect giving an IRR of 1.64 (1.48‐1.81). Conclusions: HFF remarkably conditioned the use of BDZs resulting in seriously biased IRRs when this association was studied through a SCCS design. The use of pre‐exposure periods of different lengths helped to correct this error. [ABSTRACT FROM AUTHOR]

Purpose To examine the utility of electronic health records from a routine care setting in assessing comparative effectiveness of fourth‐line anti‐hypertensive drugs to treat resistant hypertension. Methods: We conducted a cohort study using the Clinical Practice Research Datalink: a repository of electronic health records from UK primary care. We identified patients newly prescribed fourth‐line anti‐hypertensive drugs (aldosterone antagonist , beta‐blocker, or alpha‐blocker). Using propensity score–adjusted Cox proportional hazards models, we compared the incidence of the primary outcome (composite of all‐cause mortality, stroke, and myocardial infarction) between patients on different fourth‐line drugs. AA was the reference drug in all comparisons. Secondary outcomes were individual components of the primary outcome, blood pressure changes, and heart failure. We used a negative control outcome, Herpes Zoster, to detect unmeasured confounding. Results: Overall, 8639 patients were included. In propensity score–adjusted analyses, the hazard ratio for the primary outcome was 0.81 (95% CI, 0.55‐1.19) for beta‐blockers and 0.68 (95% CI, 0.46‐0.96) for alpha‐blockers versus AA. Findings for individual cardiovascular outcomes trended in a more plausible direction, albeit imprecise. A trend for a protective effect for Herpes Zoster across both comparisons was seen. Conclusions: A higher rate of all‐cause death in the AA group was likely due to unmeasured confounding in our analysis of the composite primary outcome, supported by our negative outcome analysis. Results for cardiovascular outcomes were plausible, but imprecise due to small cohort sizes and a low number of observed outcomes. [ABSTRACT FROM AUTHOR]

Aim: To estimate the risk of gastrointestinal (GI) bleeding associated with serotonin reuptake inhibitors (SSRIs) by level of kidney function. Methods: We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics. We identified patients with chronic kidney disease (CKD; estimated glomerular filtration rate <60 ml min–1 1.73 m–2 for ≥3 months), and a comparison group of patients without it. Patients with CKD were further classified as stage 3a (eGFR 45–59 ml min–1 1.73 m–2), 3b (30–44 ml min–1 1.73 m–2) and 4/5 (<30 ml min–1 1.73 m–2). We excluded prevalent SSRI users at cohort entry. Exposure was time‐dependent SSRI prescription and outcome was first hospitalization for GI bleeding. We estimated adjusted rate ratio (aRR) and rate difference (aRD) of GI bleeding comparing periods with and without SSRI prescription at each level of kidney function. Results: The aRRs and aRDs were: (i) no CKD (n = 202 121) aRR: 1.66 (95%CI 1.37–2.01), aRD: 2.0/1000 person–years (5.5 vs. 3.5/1000 person–years in period with and without SSRIs); (ii) CKD stage 3a (n = 153 316) aRR: 1.86 (1.62–2.15), aRD: 4.2/1000 person–years (8.3 vs. 4.1/1000 person–years); (iii) CKD stage 3b (n = 46 482) aRR: 1.61 (1.27–2.04), aRD: 4.8/1000 person–years (9.9 vs. 5.1/1000 person–years); and (iv) CKD stage 4/5 (n = 11 197) aRR: 1.84 (1.14–2.96), aRD: 7.9/1000 person–years (15.3 vs. 7.4/1000 person–years). While there was no evidence of increase in the aRR (P = 0.922), there was strong evidence that the aRD increased as kidney function deteriorated (P = 0.001). Conclusions: While the relative risk was constant, the excess risk of GI bleeding associated with SSRIs markedly increased among patients with decreased kidney function. [ABSTRACT FROM AUTHOR]

We describe some simple techniques for investigating 2 key assumptions of the self-controlled case series (SCCS) method, namely, that events do not influence subsequent exposures and that events do not influence the length of observation periods. For each assumption, we propose some simple tests based on the standard SCCS model, along with associated graphical displays. The methods also enable the user to investigate the robustness of the results obtained using the standard SCCS model to failure of assumptions. The proposed methods are investigated by simulations and applied to data on measles, mumps and rubella vaccine, and antipsychotics. [ABSTRACT FROM AUTHOR]

Purpose Defining a study population and creating an analytic dataset from longitudinal healthcare databases involves many decisions. Our objective was to catalogue scientific decisions underpinning study execution that should be reported to facilitate replication and enable assessment of validity of studies conducted in large healthcare databases. Methods We reviewed key investigator decisions required to operate a sample of macros and software tools designed to create and analyze analytic cohorts from longitudinal streams of healthcare data. A panel of academic, regulatory, and industry experts in healthcare database analytics discussed and added to this list. Conclusion Evidence generated from large healthcare encounter and reimbursement databases is increasingly being sought by decision-makers. Varied terminology is used around the world for the same concepts. Agreeing on terminology and which parameters from a large catalogue are the most essential to report for replicable research would improve transparency and facilitate assessment of validity. At a minimum, reporting for a database study should provide clarity regarding operational definitions for key temporal anchors and their relation to each other when creating the analytic dataset, accompanied by an attrition table and a design diagram. A substantial improvement in reproducibility, rigor and confidence in real world evidence generated from healthcare databases could be achieved with greater transparency about operational study parameters used to create analytic datasets from longitudinal healthcare databases. [ABSTRACT FROM AUTHOR]

Aim Some previous studies suggest a long term association between clarithromycin use and cardiovascular events. This study investigates this association for clarithromycin given as part of Helicobacter pylori treatment (HPT). Methods Our source population was the Clinical Practice Research Datalink (CPRD), a UK primary care database. We conducted a self-controlled case series (SCCS), a case-time-control study (CTC) and a propensity score adjusted cohort study comparing the rate of cardiovascular events in the 3 years after exposure to HPT containing clarithromycin with exposure to clarithromycin free HPT. Outcomes were first incident diagnosis of myocardial infarction (MI), arrhythmia and stroke. For the cohort analysis we included secondary outcomes all cause and cardiovascular mortality. Results Twenty-eight thousand five hundred and fifty-two patients were included in the cohort. The incidence rate ratio of first MI within 1 year of exposure to HPT containing clarithromycin was 1.07 (95% CI 0.85, 1.34, P = 0.58) and within 90 days was 1.43 (95% CI 0.99, 2.09 P = 0.057) in the SCCS analysis. CTC and cohort results were consistent with these findings. Conclusions There was some evidence for a short term association for first MI but none for a long term association for any outcome. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to evaluate the performance and validity of the case-crossover (CCO) and self-controlled case-series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case-control designs is discussed. Methods Adult patients with HF and who received an AD prescription during 2001-2009 were identified from UK's The Health Improvement Network (THIN) and the Dutch Mondriaan databases. AD exposure was classified into current, recent and past/non-use (reference). In the CCO, for each patient, a case moment (date of HF) and four prior control moments at −91, −182, −273 and −365 days were defined. In SCCS, incidence of HF was compared between exposure states. Conditional logistic regression was used in the CCO and Poisson regression in the SCCS to compute odds ratios and incidence rate ratios, respectively. In CCO, we adjusted for time-varying co-medication and in SCCS for age. Results Adjusted estimates for the effect of current AD exposure on HF were higher in the CCO (co-medication-adjusted odds ratio, THIN: 2.24, 95% confidence interval [CI]: 2.04-2.47; Mondriaan: 2.57, 95%CI [1.50, 4.43]) than in the SCCS (age-adjusted incidence rate ratio, THIN: 1.41, 95%CI [1.32, 1.49]; Mondriaan: 2.14, 95%CI [1.51, 3.03]). The latter were comparable with the traditional designs. Conclusion Case-only designs confirmed the association between AD and HF. The CCO design violated assumptions in this study with regard to exchangeability and length of exposure, and transient effects on outcome. The SCCS seems to be an appropriate design for assessing AD-HF association. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The case-crossover (CXO) and self-controlled case series (SCCS) designs are increasingly used in pharmacoepidemiology. In both, relative risk estimates are obtained within persons, implicitly controlling for time-fixed confounding variables. Objectives To examine the consistency of relative risk estimates of hip/femur fractures (HFF) associated with the use of benzodiazepines (BZD) across case-only designs in two databases (DBs), when a common protocol was applied. Methods CXO and SCCS studies were conducted in BIFAP (Spain) and CPRD (UK). Exposure to BZD was divided into non-use, current, recent and past use. For CXO, odds ratios (OR; 95%CI) of current use versus non-use/past were estimated using conditional logistic regression adjusted for co-medications (AOR). For the SCCS, conditional Poisson regression was used to estimate incidence rate ratios (IRR; 95%CI) of current use versus non/past-use, adjusted for age. To investigate possible event-exposure dependence the relative risk in the 30 days prior to first BZD exposure was also evaluated. Results In the CXO current use of BZD was associated with an increased risk of HFF in both DBs, AORBIFAP = 1.47 (1.29-1.67) and AORCPRD = 1.55 (1.41-1.70). In the SCCS, IRRs for current exposure was 0.79 (0.72-0.86) in BIFAP and 1.21 (1.13-1.30) in CPRD. However, when we considered separately the 30-day pre-exposure period, the IRR for current period was 1.43 (1.31-1.57) in BIFAP and 1.37 (1.27-1.47) in CPRD. Conclusions CXO designs yielded consistent results across DBs, while initial SCCS analyses did not. Accounting for event-exposure dependence, estimates derived from SCCS were more consistent across DBs and designs. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Purpose The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies. Methods For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments. Results Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53). Conclusion An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations. © 2015 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Purpose To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. Methods The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. Results The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. Conclusion Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care. Methods We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated. Results We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m−2, respectively. Patients receiving orlistat lost, on average, 0.94 kg month−1 (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month−1 (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month−1. Conclusions Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials. [ABSTRACT FROM AUTHOR]

Aims This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin-converting enzyme inhibitors. Methods The study included new users of angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model, adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year. Results A total of 426 089 persons were included in the primary analysis, with 45 541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin-converting enzyme inhibitors. The total number of new diagnoses of dementia was 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow-up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 0.85-1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% confidence interval 0.50-0.72). Conclusions A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin-converting enzyme inhibitors. However, the strongest association was seen in early follow-up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin-converting enzyme inhibitor users. [ABSTRACT FROM AUTHOR]

Purpose UK primary care databases are frequently used in observational studies with cancer outcomes. We aimed to systematically review methods used by such studies to identify and validate incident cancers of the breast, colorectum, and prostate. Methods Medline and Embase (1980-2013) were searched for UK primary care database studies with incident breast, colorectal, or prostate cancer outcomes. Data on the methods used for case ascertainment were extracted and summarised. Questionnaires were sent to corresponding authors to obtain details about case ascertainment. Results Eighty-four studies of breast ( n = 51), colorectal ( n = 54), and prostate cancer ( n = 31) were identified; 30 examined >1 cancer type. Among the 84 studies, 57 defined cancers using only diagnosis codes, while 27 required further evidence such as chemotherapy. Few studies described methods used to create cancer code lists ( n = 5); or made lists available directly ( n = 5). Twenty-eight code lists were received on request from study authors. All included malignant neoplasm diagnosis codes, but there was considerable variation in the specific codes included which was not explained by coding dictionary changes. Code lists also varied in terms of other types of codes included, such as in-situ, cancer morphology, history of cancer, and secondary/suspected/borderline cancer codes. Conclusions In UK primary care database studies, methods for identifying breast, colorectal, and prostate cancers were often unclear. Code lists were often unavailable, and where provided, we observed variation in the individual codes and types of codes included. Clearer reporting of methods and publication of code lists would improve transparency and reproducibility of studies. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aims To investigate whether the use of carbamazepine is associated with reduced risk of Parkinson's disease. Methods We conducted a population-based, matched case-control study of patients randomly selected from the UK General Research Practice Database. We identified 8549 patients with Parkinson's disease using diagnosis criteria with a positive predictive value of 90%. These patients were compared with 42 160 control subjects matched for age, sex and general practice. Results Overall, 3.0% of cases (257 of 8549) had at least one recorded prescription for carbamazepine compared with 2.5% (1050 of 42 160) of controls. The crude odds ratio for the association between Parkinson's disease and carbamazepine was 1.22 (95% confidence interval 1.06-1.40), but this reduced to 0.93 (95% confidence interval 0.81-1.08, P = 0.34) after adjusting for annual consultation rate. Further adjustment for body mass index, smoking status, alcohol consumption or use of calcium channel blockers did not affect results. There was no evidence that risk decreased with higher doses or longer duration of carbamazepine use. Conclusions There was little to no evidence that use of carbamazepine is associated with reduced risk of Parkinson's disease. Although the study was underpowered, it does indicate that any effect of carbamazepine is likely to be small. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • An unfavourable risk profile for myocardial infarction (MI) is associated with various lifestyle factors and co-morbidities that are more prevalent among patients with severe mental illness. • Patient populations that are prescribed antipsychotic agents have a higher cardiovascular mortality rate than the general population. • The association between the use of antipsychotic agents and any increase in the risk of MI is unclear. WHAT THIS STUDY ADDS • The aim of this systematic literature review was to assess the relationship between antipsychotic agents and MI. • Substantial clinical and methodological heterogeneity between the five studies in this review led to an inconclusive answer to the question whether the use of antipsychotics is associated with the incidence of MI in adults. • The largest study had a favourable internal validity compared with the other studies and did not find an association between the use of antipsychotic agents and an increased risk of MI. AIM Patient populations that are prescribed antipsychotic agents have higher cardiovascular mortality rates. The risk of myocardial infarction is influenced by various factors that are more prevalent in patients with a mental illness. The aim of this review was to determine whether the use of antipsychotic agents is associated with the incidence of myocardial infarction in adults. METHODS Using multiple sources, all studies of antipsychotic agents using myocardial infarction as primary or secondary outcome measures were considered for inclusion. Study populations were adult subjects who had been prescribed an antipsychotic agent at least once in their medical history. RESULTS It total, five studies were identified. Four studies with small numbers of events reported a moderate to strong effect of typical antipsychotic agents on the risk of myocardial infarction. The largest study had a favourable internal validity compared with all other studies and reported no association between the risk of myocardial infarction and current use of either atypical (relative risk 0.98, 95% confidence interval [CI] 0.88, 1.09) or typical antipsychotic agents (relative risk 0.99, 95% CI 0.96, 1.03). CONCLUSION Clinical and methodological heterogeneity between the studies in this review led to an inconclusive answer to the question whether the use of antipsychotics is associated with the incidence of myocardial infarction in adults. Whilst results conflicted, the largest study did not find an association between the use of antipsychotic agents and an increased risk of myocardial infarction. [ABSTRACT FROM AUTHOR]

• Selective serotonin re-uptake inhibitors (SSRI) are associated with an increased risk of bleeding disorders at a number of sites. • It is currently unclear whether they increase the risk of haemorrhagic stroke, with conflicting results reported. • We found no association between SSRI use and haemorrhagic stroke. • The large number of patients involved in the study allowed us to rule out any substantial effect. • The results were similar in people with and without a previous history of cerebrovascular events. To investigate whether selective serotonin re-uptake inhibitor (SSRI) use is associated with an increased risk of haemorrhagic stroke in a cohort of antidepressant users. We conducted a case control study, nested within a cohort of antidepressant users in the United Kingdom General Practice Research Database. A cohort of 365 195 patients prescribed either an SSRI or tricyclic antidepressant between 1992 and 2006 was identified. Three hundred and fifty-seven cases of haemorrhagic stroke were observed and 1631 control patients without haemorrhagic stroke were selected. The primary analysis showed no evidence of an association between current SSRI or TCA use and haemorrhagic stroke. Current use of an SSRI compared with no use at the time of haemorrhagic stroke was associated with an adjusted odds ratio of 1.11 (95% confidence interval (CI) 0.82, 1.50). For current tricyclic use the equivalent odds ratio was 0.73 (0.52, 1.02). There was no evidence that prior cerebrovascular events modified the effect of either SSRIs or TCAs. We found no evidence that SSRIs are associated with an increased risk of haemorrhagic stroke, regardless of prior history of cerebrovascular events. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Conflicting studies have raised uncertainty over the vascular effects of the long-acting anticholinergic, tiotropium bromide. WHAT THIS STUDY ADDS • Our results show no increased risk of stroke with tiotropium bromide, or with inhaled anticholinergics in general. AIMS A recent communication from the United States Food and Drug Administration highlighted a possible increased risk of stroke associated with use of the relatively new inhaled anticholinergic drug, tiotropium bromide. Using the United Kingdom General Practice Research Database, we set out to assess the risk of stroke in individuals exposed to inhaled tiotropium bromide and two other inhaled treatments for airways disease. METHODS We used the self-controlled case-series that reduces confounding and minimizes the potential for biases in the quantification of risk estimates. RESULTS Of 1043 people with a diagnosis of incident stroke who had had at least one prescription for tiotropium bromide, 980 satisfied inclusion criteria. The age-adjusted incidence rate ratio for all-cause stoke in individuals exposed to tiotropium bromide ( n= 980), ipratropium bromide ( n= 4181) and fluticasone propionate/salmeterol xinafoate ( n= 1000) was 1.1 [95% confidence interval (CI) 0.9, 1.3], 0.8 (95% CI 0.7, 0.9) and 1.0 (95% CI 0.9, 1.2), respectively. CONCLUSIONS We found no evidence of an increased risk of all-cause stroke for individuals exposed to commonly prescribed inhaled treatments for chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The effect of statins on cardiovascular outcomes is well established. • Effects on numerous other health outcomes have been claimed, but results have been inconsistent. • Previous observational studies may have been affected by selection bias and confounding. WHAT THIS STUDY ADDS • This study was larger and more statistically powerful than the combined total of data from all randomized trials of statins undertaken to date. • The validity of the study is supported by findings for vascular outcomes being comparable to those observed in large randomized controlled trials. • There was little evidence to support effects of statins beyond their established effects on cardiovascular disease. AIMS To assess the effect of statins on a range of health outcomes. METHODS We undertook a population-based cohort study to assess the effect of statins on a range of health outcomes using a propensity score-based method to control for differences between people prescribed and not prescribed statins. We validated our design by comparing our results for vascular outcomes with the effects established in large randomized trials. The study was based on the United Kingdom Health Improvement Network database that includes the computerized medical records of over four and a half million patients. RESULTS People who initiated treatment with a statin ( n = 129 288) were compared with a matched sample of 600 241 people who did not initiate treatment, with a median follow-up period of 4.4 years. Statin use was not associated with an effect on a wide range of outcomes, including infections, fractures, venous thromboembolism, gastrointestinal haemorrhage, or on specific eye, neurological or autoimmune diseases. A protective effect against dementia was observed (hazard ratio 0.80, 99% confidence interval 0.68, 0.95). There was no effect on the risk of cancer even after ≥8 years of follow-up. The effect sizes for statins on vascular end-points and mortality were comparable to those observed in large randomized trials, suggesting bias and confounding had been well controlled for. CONCLUSIONS We found little evidence to support wide-ranging effects of statins on health outcomes beyond their established beneficial effect on vascular disease. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Randomized controlled trials are the gold standard of drug efficacy assessment, but have limited power to assess adverse drug reactions. • Observational data derived from larger populations of patients are often affected by confounding variables, many of which are difficult to measure or simply not known. WHAT THIS STUDY ADDS • This study demonstrates the utility of the self-controlled case-series method of analysing the safety profile of drugs, which reduces confounding because comparisons are intraperson. • Although such data should not be viewed in isolation, the efficiency and versatility of this method suggest that it could become a future standard in drug safety assessment. AIMS Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. METHODS We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. RESULTS Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens–Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. CONCLUSIONS Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs. [ABSTRACT FROM AUTHOR]

To help improve the well-being of the local people, a joint Vietnamese-UK team set out to establish a way of estimating soil and nutrient losses under different land management scenarios, using field data extrapolated through remote sensing and GIS, to obtain catchment-wide estimates of the impact of land cover change. Immigration from remote provinces to the Dong Phu District of Binh Phuóc Province, about 120 km north of Ho Chi Minh City, has led to disruption of soil surface stability on easily eroded clayey sandstones, creating rapid nutrient depletion that affects crop yields and siltation in the channel of the Rach Rat river downstream. The poor farmers of the areas see crop yields drop dramatically after two or three years of cultivation due to the fertility decline. Soil loss varies dramatically between wet season and dry season and with ground cover. Erosion bridge measurements showed a mean loss of 85.2 t ha−1 y−1 under cassava saplings with cashew nuts, 43.3 t ha−1 y−1 on uncultivated land and 41.7 t ha−1 y−1 under mature cassava. The rates of erosion were higher than those reported in many other parts of Vietnam, reflecting the high erodibility of the friable sandy soils on the steep side-slopes of the Rach Rat catchment. However, although the actual measurements provide better soil loss data than estimates based on the parameters of soil loss equations, a large number of measurement sites is needed to provide adequate coverage of the crop and slope combinations in this dissected terrain for good prediction using GIS and remote sensing. [ABSTRACT FROM AUTHOR]

Several parts of Binh Phuóc Province, southern Vietnam, suffer from degraded soils and vegetation as a result of both natural erosion of weak mud rocks and sandstones and intensive human activity, especially through land clearing for agriculture on unstable slopes, deforestation, and abandonment of poor farmland. The underlying cause of this land degradation has been the farming habits of migrants of varying ethnic groups who have settled in the area since 1980. The indigenous farming knowledge of these people and the role of that knowledge in soil erosion were examined by a series of household surveys. They enabled farming practices to be related to ground cover established from a 2002 Landsat 7 ETM (Enhanced Thematic Mapper), and erosion data from a series of erosion bridge measurements. A GIS (Geographical Information System) approach was piloted as a means of identifying areas vulnerable to erosion. This could then be combined with the understanding of farming practices to reveal the relative roles of farmer behaviour, crop cover, and slope and soil characteristics in the erosion process. Land use, local people's knowledge and economic realities are the main factors, as well as natural conditions, that drive this land degradation. [ABSTRACT FROM AUTHOR]

Economic globalisation has led to a huge increase in demand for food, goods and services by expanding urban middle class populations. These demands cause environmental changes that in turn feed back upon the urban environment and human population. While the global changes are well researched, the cumulative significance of local environmental changes is less well known. Yet, the local changes may have greater impact on the decisions which individuals make that affect soil erosion and land degradation. People respond to family circumstances and to local economic opportunities in ways that most suit the needs of their families and households. Several demonstration projects that were not adopted offer lessons in understanding how people make their land-use decisions. An understanding of people's past experiences, present needs and views of the future helps those seeking to improve environmental management to promote policies and actions that are likely to succeed by being acceptable to those involved. [ABSTRACT FROM AUTHOR]

Presents information on a study that compares oocyst-sized microspheres and Cryptosporidium parvum (C. parvum) removal during late in-cycle filtration. Variation in the ability of filters to remove C. parvum; Analysis of C. parvum and microsphere; Conclusions of the study.

To assess current practices in the labour management of low risk primiparous women with epidural analgesia we surveyed delivery suites in New South Wales (NSW) that annually provide at least 100 epidurals to ‘standard primipara’. Epidural rates among ‘standard primipara’ at these hospitals ranged from 14 to 85% (median 46%). Continuous epidural infusion was the most commonly used technique (63%). For ‘standard primipara’ with an epidural 62% of units usually augmented labour with oxytocin, 89% discontinued the epidural in second stage and 67% had policies of delayed pushing. There is wide variation in epidural availability and in labour management, perhaps reflecting the limited evidence for effective interventions to reduce any unintended effects of epidural analgesia. [ABSTRACT FROM AUTHOR]

Abstract The biomass and biomass dynamics of forests are major uncertainties in our understanding of tropical environments. Remote sensing is often the only practical means of acquiring information on forest biomass but has not always been used successfully. Here the conventional approaches to the estimation of forest biomass from remotely sensed data were evaluated relative to techniques based on the application of artificial neural networks. Together these approaches were used to estimate and map the biomass of tropical forests in north-eastern Borneo from Landsat TM data. The neural networks were found to be particularly suited to the application. A basic multi-layer perceptron network, for example, provided estimates of biomass that were strongly correlated with those measured in the field (r = 0.80). Moreover, these estimates were more strongly correlated with biomass than those derived from 230 conventional vegetation indices, including the widely used normalized difference vegetation index (NDVI). [ABSTRACT FROM AUTHOR]

The transfer of materials from the natural environment to the urban and industrially built environment produces two broad impacts on the landscape: a removal of materials from the earth's surface (a change in geomorphology) and the accumulation of a stock of concrete and other materials elsewhere in cities and industrial zones (a change in urban morphology). Thus, industrial activity transforms natural landscapes and, in doing so, has to be considered to be a geological and geomorphological agent. On the global scale, the deliberate shift of around 57,000 Mt (megatons)/yr of materials through mineral extraction processes exceeds the annual transport of sediment to the oceans by rivers (some 22,000 Mt/yr) by almost a factor of three. On the island of Britain, the total deliberate shift of earth-surface materials is between 688 and 972 Mt/yr, depending on whether or not the replacement of overburden in opencast coal mining is taken into account.The export of sediment to the oceans by rivers is only 10 Mt/yr whereas the export of materials in solution is about 40 Mt/yr, making the deliberate materials shift nearly 14 times larger than the shift caused by natural processes. Processes examined by industrial ecology, such as direct excavation, urban development, and waste dumping are those most driving changes in the shape of the British landscape today.These transformations pose added costs. Industrial ecology will produce an understanding of the hidden costs associated with these transformations. Such an understanding will help in planning and encouraging the reuse of materials everywhere and in identifying the key areas for intervention to reduce off-site geomorphological impacts and costs. [ABSTRACT FROM AUTHOR]

Pressure from the state government to abandon shifting cultivation and of the market to increase the production of cash crops are causing not simply a reduction in the practice of shifting cultivation in Sabah, Malaysia but marked alterations in the way many remote communities grow hill rice. Many traditional practices have been abandoned including the substitution of cash payments for community labour co-operation (gotong-royong), the use of traditional methods to monitor soil fertility such as maintaining fallow periods and the selection of appropriate hill rice varieties. The result has been a reduction in labour input, a shortage of land, continuous production, increased used of weedicides and a general failure to continue sustainable agricultural practices. Despite state incentives to abandon the practice the pressure to maintain real incomes among the rural communities has meant a continuation of the practice of shifting cultivation but under conditions which are now resulting in land degradation, slope instability and soil infertility. [ABSTRACT FROM AUTHOR]

ABSTRACT Resource development in the form of cyclical commercial logging activities results in a short period of often severe land disturbance followed by a prolonged phase of recovery. The monitoring of catchment sediment yield gives some indication of the gross erosion processes within the catchment as a result of the disturbance and may also effectively measure any ameliorative processes. Studies in Ulu Segama, Sabah, East Malaysia, recorded significant increases in stream suspended sediment loads as a result of logging. Stream loads were derived from a combination of daily sample measurements and storm event sampling using automated liquid samplers. Measured loads were then compared to computed loads from sediment discharge rating sets derived from the actual samples. Application of these ratings in the disturbed catchment initially underestimated sediment loads; however, a progressive overestimation of loads occurred as the catchment vegetation recovered. When using sediment rating curves as a tool to measure catchment erosion rates in disturbed environments, considerable caution has to be used. Vegetation recovery is reflected in the rapid recovery of stream water quality, making it necessary to continually review the rating. [ABSTRACT FROM AUTHOR]

ABSTRACT In the 1950s, few people had travelled widely through different parts of the tropics and interpretations on tropical landforms, soils, vegetation and climate largely rested on impressions gained from residence or long sojourns in particular tropical countries. Most academic geography on the tropics was then written by expatriates and lacked the perspective gained from long experience of tropical regions. Particular problems of understanding arose as people attempted to extrapolate from one part of the tropics to another. Since then, understanding has advanced enormously, largely through the efforts of tropical scientists working in their own institutions and through the greater technological ability to study tropical lands both remotely and through easier field access. The establishment of a number of field stations, aimed primarily at the biological sciences, but also facilitating the work of geographers, has been a major stimulus to this effort. Concerns over practical issues, particularly local development and global climatic change have prompted new avenues of research, many of which have been assisted by the great increase in data collection in tropical countries. For the future, South-South dialogue between tropical physical geographers is needed to improve their ability to ask meaningful questions so that they can contribute to teach the rest of their discipline more about serious applied and applicable geography. [ABSTRACT FROM AUTHOR]