Evaluation of computer based clinical decision support system and risk chart for management of hypertension in primary care: randomised controlled trial

ObjectivesTo investigate the effect of a computer based clinical decision support system and a risk chart on absolute cardiovascular risk, blood pressure, and prescribing of cardiovascular drugs in hypertensive patients.DesignCluster randomised controlled trial.Setting27 general practices in Avon.Participants614 patients aged between 60 and 79 years with high blood pressure.InterventionsPatients were randomised to computer based clinical decision support system plus cardiovascular risk chart; cardiovascular risk chart alone; or usual care.ResultsPatients in the computer based clinical decision support system and chart only groups were no more likely to have cardiovascular risk reduced to below 10% than patients receiving usual care. Patients in the computer based clinical decision support group were more likely to have a cardiovascular risk ⩾10% than chart only patients, odds ratio 2.3 (95% confidence interval 1.1 to 4.8). The chart only group had significantly lower systolic blood pressure compared with the usual care group (difference in means −4.6 mm Hg (95% confidence interval −8.4 to −0.8)). Reduction of diastolic blood pressure did not differ between the three groups. The chart only group were twice as likely to be prescribed two classes of cardiovascular drugs and over three times as likely to be prescribed three or more classes of drugs compared with the other groups.ConclusionsThe computer based clinical decision support system did not confer any benefit in absolute risk reduction or blood pressure control and requires further development and evaluation before use in clinical care can be recommended. Use of chart guidelines are associated with a potentially important reduction in systolic blood pressure.     

NHSnet in Scottish primary care: lessons for the future

ObjectiveTo evaluate the primary care communications initiative, which introduced NHSnet to primary care in Scotland.DesignSemi-structured telephone interviews, postal questionnaire.SettingAll 15 Scottish health boards, random sample of 1 in 3 of all Scottish general practices.ParticipantsInformation management and technology managers of health boards, 355 practice managers in the general practices.Results99% of Scottish general practices agreed to participate in initiative. Health boards varied significantly in project management styles (from minimal to total control), the nature of the networks they established (intranets or direct connections), costs to practices (from nothing to £125 per general practitioner per year), and training provided (from none to an extensive programme). In 56% of practices someone accessed NHSnet at least once a week. Practices varied considerably in amount of internet training received and staff groups targeted and in the intention to provide desktop access to NHSnet through a practice network.ConclusionThe initiative has successfully introduced a network that links Scottish general practices, health boards, and hospital trusts. However local variation in this “national” initiative may affect its use in primary care. Health authorities and general practices in England and Wales may wish to note these findings in order to avoid unhelpful variation.     

Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study

ObjectiveTo investigate the influence of weight reduction on obese patients with asthma.DesignOpen study, two randomised parallel groups.SettingPrivate outpatients centre, Helsinki, Finland.ParticipantsTwo groups of 19 obese patients with asthma (body mass index (kg/m²) 30 to 42) recruited through newspaper advertisements.InterventionSupervised weight reduction programme including 8 week very low energy diet.ResultsAt the end of the weight reducing programme, the participants in the treatment group had lost a mean of 14.5% of their pretreatment weight, the controls 0.3%. The corresponding figures after one year were 11.3% and a weight gain of 2.2%. After the 8 week dieting period the difference in changes in percentage of predicted FEV₁ from baseline in the treatment and control groups was 7.2% (95% confidence interval 1.9% to 12.5%, P=0.009). The corresponding difference in the changes in FVC was 8.6% (4.8% to 12.5%, P<0.0001). After one year the differences in the changes in the two groups were still significant: 7.6% for FEV₁ (1.5% to 13.8%, P=0.02) and 7.6% for FVC (3.5% to 11.8%, P=0.001). By the end of the weight reduction programme, reduction in dyspnoea was 13 mm (on a visual analogue scale 0 mm to 100 mm) in the treatment group and 1 mm in the control group (P=0.02). The reduction of rescue medication was 1.2 and 0.1 doses respectively (P=0.03). After one year the differences in the changes between the two groups were −12 for symptom scores (range −1 to −22, P=0.04) and −10 for total scores (−18 to −1, P=0.02). The median number of exacerbations in the treatment group was 1 (0-4) and in the controls 4 (0-7), P=0.001.ConclusionWeight reduction in obese patients with asthma improves lung function, symptoms, morbidity, and health status.     

Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women

BackgroundEpidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.MethodsThe study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1₁₉₂ and PON1₋₁₀₈) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.ResultsInfants'' PON1 genotype and activity were associated with birth outcome, but mothers'' were not. Infants with the susceptible PON1_−108TT genotype had shorter gestational age (β = −0.5 weeks, 95% Confidence Interval (CI): −0.9, 0.0) and smaller head circumference (β = −0.4 cm, 95% CI: −0.7, 0.0) than those with the PON1_−108CC genotype. Infants'' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1_−108TT genotype (p-value_interaction = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value_interaction = 0.06) and head circumference (p-value_interaction<0.01) in infants with non-susceptible genotypes.ConclusionsInfants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.     

Effectiveness of Group Problem Management Plus,a brief psychological intervention for adults affected by humanitarian disasters in Nepal: A cluster randomized controlled trial

BackgroundGlobally, 235 million people are impacted by humanitarian emergencies worldwide, presenting increased risk of experiencing a mental disorder. Our objective was to test the effectiveness of a brief group psychological treatment delivered by trained facilitators without prior professional mental health training in a disaster-prone setting.Methods and findingsWe conducted a cluster randomized controlled trial (cRCT) from November 25, 2018 through September 30, 2019. Participants in both arms were assessed at baseline, midline (7 weeks post-baseline, which was approximately 1 week after treatment in the experimental arm), and endline (20 weeks post-baseline, which was approximately 3 months posttreatment). The intervention was Group Problem Management Plus (PM+), a psychological treatment of 5 weekly sessions, which was compared with enhanced usual care (EUC) consisting of a family psychoeducation meeting with a referral option to primary care providers trained in mental healthcare. The setting was 72 wards (geographic unit of clustering) in eastern Nepal, with 1 PM+ group per ward in the treatment arm. Wards were eligible if they were in disaster-prone regions and residents spoke Nepali. Wards were assigned to study arms based on covariate constrained randomization. Eligible participants were adult women and men 18 years of age and older who met screening criteria for psychological distress and functional impairment. Outcomes were measured at the participant level, with assessors blinded to group assignment. The primary outcome was psychological distress assessed with the General Health Questionnaire (GHQ-12). Secondary outcomes included depression symptoms, posttraumatic stress disorder (PTSD) symptoms, “heart–mind” problems, social support, somatic symptoms, and functional impairment. The hypothesized mediator was skill use aligned with the treatment’s mechanisms of action. A total of 324 participants were enrolled in the control arm (36 wards) and 319 in the Group PM+ arm (36 wards). The overall sample (N = 611) had a median age of 45 years (range 18–91 years), 82% of participants were female, 50% had recently experienced a natural disaster, and 31% had a chronic physical illness. Endline assessments were completed by 302 participants in the control arm (36 wards) and 303 participants in the Group PM+ arm (36 wards). At the midline assessment (immediately after Group PM+ in the experimental arm), mean GHQ-12 total score was 2.7 units lower in Group PM+ compared to control (95% CI: 1.7, 3.7, p < 0.001), with standardized mean difference (SMD) of −0.4 (95% CI: −0.5, −0.2). At 3 months posttreatment (primary endpoint), mean GHQ-12 total score was 1.4 units lower in Group PM+ compared to control (95% CI: 0.3, 2.5, p = 0.014), with SMD of −0.2 (95% CI: −0.4, 0.0). Among the secondary outcomes, Group PM+ was associated with endline with a larger proportion attaining more than 50% reduction in depression symptoms (29.9% of Group PM+ arm versus 17.3% of control arm, risk ratio = 1.7, 95% CI: 1.2, 2.4, p = 0.002). Fewer participants in the Group PM+ arm continued to have “heart–mind” problems at endline (58.8%) compared to the control arm (69.4%), risk ratio = 0.8 (95% CI, 0.7, 1.0, p = 0.042). Group PM+ was not associated with lower PTSD symptoms or functional impairment. Use of psychosocial skills at midline was estimated to explain 31% of the PM+ effect on endline GHQ-12 scores. Adverse events in the control arm included 1 suicide death and 1 reportable incidence of domestic violence; in the Group PM+ arm, there was 1 death due to physical illness. Study limitations include lack of power to evaluate gender-specific effects, lack of long-term outcomes (e.g., 12 months posttreatment), and lack of cost-effectiveness information.ConclusionsIn this study, we found that a 5-session group psychological treatment delivered by nonspecialists modestly reduced psychological distress and depression symptoms in a setting prone to humanitarian emergencies. Benefits were partly explained by the degree of psychosocial skill use in daily life. To improve the treatment benefit, future implementation should focus on approaches to enhance skill use by PM+ participants.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03747055","term_id":"NCT03747055"}}NCT03747055.

Mark Jordans and co-workers evaluate a group therapy intervention in adults affected by psychological distress in Nepal.     

Human leukocyte antigen genotype and risk of HIV disease progression before and after initiation of antiretroviral therapy

While the human leukocyte antigen (HLA) genotype has been associated with the rate of HIV disease progression in untreated patients, little is known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited data reported to date identified few HLA-HIV disease associations in patients using HAART and even occasional associations that were opposite of those found in untreated patients. We conducted high-resolution HLA class I and II genotyping in a random sample (n = 860) of HIV-seropositive women enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using multivariate analyses. In untreated HIV-seropositive patients, we observed many of the predicted associations, consistent with prior studies. For example, HLA-B*57 (β = −0.7; 95% confidence interval [CI] = −0.9 to −0.5; P = 5 × 10⁻¹¹) and Bw4 (β = −0.2; 95% CI = −0.4 to −0.1; P = 0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with a low risk of rapid CD4⁺ decline (odds ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated patients, the odds of a virological response to HAART were lower for B*57:01 (OR = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P = 0.04) was associated with low odds of an immunological response. The associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and untreated patients.     

Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review

ObjectiveTo evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome.DesignSystematic review of published randomised, placebo controlled trials.ResultsOverall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was −0.028 (95% confidence interval −0.017 to −0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was −0.036 (−0.014 to −0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens.ConclusionThe evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.

What is already known on this topic

The premenstrual syndrome affects about 1.5 million women in the United KingdomThere are numerous treatment options, progesterone being one of the most strongly advocatedProgesterone and progestogens are among the most widely prescribed treatments for premenstrual syndrome in the United Kingdom and the United States

What this study adds

There is no evidence to support the claimed efficacy of progesterone in the management of premenstrual syndromeThere is insufficient evidence to make a definitive statement about progestogens, but current evidence suggests that they are not likely to be effective     

Randomised controlled trial of midwife led debriefing to reduce maternal depression after operative childbirth

ObjectiveTo assess the effectiveness of a midwife led debriefing session during the postpartum hospital stay in reducing the prevalence of maternal depression at six months postpartum among women giving birth by caesarean section, forceps, or vacuum extraction.DesignRandomised controlled trial.SettingLarge maternity teaching hospital in Melbourne, Australia.Participants1041 women who had given birth by caesarean section (n= 624) or with the use of forceps (n= 353) or vacuum extraction (n= 64).Results917 (88%) of the women recruited responded to the outcome questionnaire. More women allocated to debriefing scored as depressed six months after birth than women allocated to usual postpartum care (81 (17%) v 65 (14%)), although this difference was not significant (odds ratio=1.24, 95% confidence interval 0.87 to 1.77). They were also more likely to report that depression had been a problem for them since the birth, but the difference was not significant (123 (28%) v 94 (22%); odds ratio=1.37, 1.00 to 1.86). Women allocated to debriefing had poorer health status on seven of the eight SF-36 subscales, although the difference was significant only for role functioning (emotional): mean scores 73.32 v 78.98, t= −2.31, 95% confidence interval −10.48 to −0.84).ConclusionsMidwife led debriefing after operative birth is ineffective in reducing maternal morbidity at six months postpartum. The possibility that debriefing contributed to emotional health problems for some women cannot be excluded.     

Pragmatic randomised controlled trial to evaluate guidelines for the management of infertility across the primary care-secondary care interface

ObjectiveTo investigate the effect of clinical guidelines on the management of infertility across the primary care-secondary care interface.DesignCluster randomised controlled trial.SettingGeneral practices and NHS hospitals accepting referrals for infertility in the Greater Glasgow Health Board area.ParticipantsAll 221 general practices in Glasgow; 214 completed the trial.InterventionGeneral practices in the intervention arm received clinical guidelines developed locally. Control practices received them one year later. Dissemination of the guidelines included educational meetings.ResultsData on 689 referrals were collected. No significant difference was found in referral rates for infertility. Fewer than 1% of couples were referred inappropriately early. Referrals from intervention practices were significantly more likely to have all relevant investigations carried out (odds ratio 1.32, 95% confidence interval 1.00 to 1.75, P=0.025). 70% of measurements of serum progesterone concentrations during the midluteal phase and 34% of semen analyses were repeated at least once in hospital, despite having been recorded as normal when checked in general practice. No difference was found in the proportion of referrals in which a management plan was reached within one year or in the mean duration between first appointment and date of management plan. NHS costs were not significantly affected.ConclusionsDissemination of infertility guidelines by commonly used methods results in a modest increase in referrals having recommended investigations completed in general practice, but there are no detectable differences in outcome for patients or reduction in costs. Clinicians in secondary care tended to fail to respond to changes in referral practice by doctors. Guidelines that aim to improve the referral process need to be disseminated and implemented so as to lead to changes in both primary care and secondary care.

What is already known on this topic

Most previous research into clinical guidelines has focused on their development and implementationEvidence is lacking about the outcomes and costs associated with the use of clinical guidelines

What this study adds

Clinical guidelines that may alter the balance of care between general practice and hospital settings require more intensive implementation than guidelines aimed at either setting on its ownThe cost effectiveness of clinical guidelines should not be assumed     

Carbon stocks and fluxes in tropical lowland dipterocarp rainforests in Sabah, Malaysian Borneo

Deforestation in the tropics is an important source of carbon C release to the atmosphere. To provide a sound scientific base for efforts taken to reduce emissions from deforestation and degradation (REDD+) good estimates of C stocks and fluxes are important. We present components of the C balance for selectively logged lowland tropical dipterocarp rainforest in the Malua Forest Reserve of Sabah, Malaysian Borneo. Total organic C in this area was 167.9 Mg C ha⁻¹±3.8 (SD), including: Total aboveground (TAGC: 55%; 91.9 Mg C ha⁻¹±2.9 SEM) and belowground carbon in trees (TBGC: 10%; 16.5 Mg C ha⁻¹±0.5 SEM), deadwood (8%; 13.2 Mg C ha⁻¹±3.5 SEM) and soil organic matter (SOM: 24%; 39.6 Mg C ha⁻¹±0.9 SEM), understory vegetation (3%; 5.1 Mg C ha⁻¹±1.7 SEM), standing litter (<1%; 0.7 Mg C ha⁻¹±0.1 SEM) and fine root biomass (<1%; 0.9 Mg C ha⁻¹±0.1 SEM). Fluxes included litterfall, a proxy for leaf net primary productivity (4.9 Mg C ha⁻¹ yr⁻¹±0.1 SEM), and soil respiration, a measure for heterotrophic ecosystem respiration (28.6 Mg C ha⁻¹ yr⁻¹±1.2 SEM). The missing estimates necessary to close the C balance are wood net primary productivity and autotrophic respiration.Twenty-two years after logging TAGC stocks were 28% lower compared to unlogged forest (128 Mg C ha⁻¹±13.4 SEM); a combined weighted average mean reduction due to selective logging of −57.8 Mg C ha⁻¹ (with 95% CI −75.5 to −40.2). Based on the findings we conclude that selective logging decreased the dipterocarp stock by 55–66%. Silvicultural treatments may have the potential to accelerate the recovery of dipterocarp C stocks to pre-logging levels.     

The impact of removing financial incentives and/or audit and feedback on chlamydia testing in general practice: A cluster randomised controlled trial (ACCEPt-able)

BackgroundFinancial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT), to our knowledge. This trial aimed to determine whether chlamydia testing in general practice is sustained when financial incentives and/or audit/feedback are removed.Methods and findingsWe undertook a 2 × 2 factorial cluster RCT in 60 general practices in 4 Australian states targeting 49,525 patients aged 16–29 years for annual chlamydia testing. Clinics were recruited between July 2014 and September 2015 and were followed for up to 2 years or until 31 December 2016. Clinics were eligible if they were in the intervention group of a previous cluster RCT where general practitioners (GPs) received financial incentives (AU$5–AU$8) for each chlamydia test and quarterly audit/feedback reports of their chlamydia testing rates. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained (group A), audit/feedback removed but incentives retained (group B), both removed (group C), or both retained (group D). The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients, where the numerator was the number who had at least 1 chlamydia test within 12 months and the denominator was the number who had at least 1 consultation during the same 12 months. We undertook a factorial analysis in which we investigated the effects of removal versus retention of incentives (groups A + C versus groups B + D) and the effects of removal versus retention of audit/feedback (group B + C versus groups A + D) separately. Of 60 clinics, 59 were randomised and 55 (91.7%) provided data (group A: 15 clinics, 11,196 patients; group B: 14, 11,944; group C: 13, 11,566; group D: 13, 14,819). Annual testing decreased from 20.2% to 11.7% (difference −8.8%; 95% CI −10.5% to −7.0%) in clinics with incentives removed and decreased from 20.6% to 14.3% (difference −7.1%; 95% CI −9.6% to −4.7%) where incentives were retained. The adjusted absolute difference in treatment effect was −0.9% (95% CI −3.5% to 1.7%; p = 0.2267). Annual testing decreased from 21.0% to 11.6% (difference −9.5%; 95% CI −11.7% to −7.4%) in clinics where audit/feedback was removed and decreased from 19.9% to 14.5% (difference −6.4%; 95% CI −8.6% to −4.2%) where audit/feedback was retained. The adjusted absolute difference in treatment effect was −2.6% (95% CI −5.4% to −0.1%; p = 0.0336). Study limitations included an unexpected reduction in testing across all groups impacting statistical power, loss of 4 clinics after randomisation, and inclusion of rural clinics only.ConclusionsAudit/feedback is more effective than financial incentives of AU$5–AU$8 per chlamydia test at sustaining GP chlamydia testing practices over time in Australian general practice.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12614000595617

In a cluster randomized trial, Jane S Hocking and colleagues investigate the impact of removing financial incentives and/or audit and feedback on chlamydia testing in general practice in Australia.     

Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study

BackgroundPrior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development.Methods and findingsThis study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10–15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents’ education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: −1.2 to −0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: −1.0 to −0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (−1.2, 95% CI: −1.6, −0.9, p < 0.001), offspring cognitive ability in 2012 (−0.6, 95% CI: −0.8, −0.3, p < 0.001), offspring depression status (−0.7, 95% CI: −1.0, −0.5, p < 0.001), and parents’ cognitive ability (−0.8, 95% CI: −1.2, −0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10–11 years) than the older ones (i.e., 12–15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be −2.1 (95% CI: −2.6, −1.6, p < 0.001) in those aged 10–11 years, compared to −1.2 (95% CI: −1.6, −0.8, p < 0.001) in those aged 12–15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding.ConclusionsIn this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.

In this cohort study, Zhihui Li and colleagues explore associations between parental depression and offspring cognitive development up to six years later.     

Stability of thioester intermediates in ubiquitin‐like modifications

Ubiquitin-like modifications are important mechanisms in cellular regulation, and are carried out through several steps with reaction intermediates being thioester conjugates of ubiquitin-like proteins with E1, E2, and sometimes E3. Despite their importance, a thorough characterization of the intrinsic stability of these thioester intermediates has been lacking. In this study, we investigated the intrinsic stability by using a model compound and the Ubc9∼SUMO-1 thioester conjugate. The Ubc9∼SUMO-1 thioester intermediate has a half life of approximately 3.6 h (hydrolysis rate k = 5.33 ± 2.8 ×10⁻⁵ s⁻¹), and the stability decreased slightly under denaturing conditions (k = 12.5 ± 1.8 × 10⁻⁵ s⁻¹), indicating a moderate effect of the three-dimensional structural context on the stability of these intermediates. Binding to active and inactive E3, (RanBP2) also has only a moderate effect on the hydrolysis rate (13.8 ± 0.8 × 10⁻⁵ s⁻¹ for active E3 versus 7.38 ± 0.7 × 10⁻⁵ s⁻¹ for inactive E3). The intrinsically high stability of these intermediates suggests that unwanted thioester intermediates may be eliminated enzymatically, such as by thioesterases, to regulate their intracellular abundance and trafficking in the control of ubiquitin-like modifications.     

"Hospital at home" versus hospital care in patients with exacerbations of chronic obstructive pulmonary disease: prospective randomised controlled trial

ObjectivesTo compare “hospital at home” and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease.DesignProspective randomised controlled trial with three months'' follow up.SettingUniversity teaching hospital offering secondary care service to 350 000 patients.PatientsSelected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment.InterventionsNurse administered home care was provided as an alternative to inpatient admission.Results583 patients with chronic obstructive pulmonary disease referred for admission were assessed. 192 met the criteria for home care, and 42 refused to enter the trial. 100 were randomised to home care and 50 to hospital care. On admission, FEV₁ after use of a bronchodilator was 36.1% (95% confidence interval 2.4% to 69.8%) predicted in home care and 35.1% (6.3% to 63.9%) predicted in hospital care. No significant difference was found in FEV₁ after use of a bronchodilator at two weeks (42.6%, 3.4% to 81.8% versus 42.1%, 5.1% to 79.1%) or three months (41.5%, 8.2% to 74.8% versus 41.9%, 6.2% to 77.6%) between the groups. 37% of patients receiving home care and 34% receiving hospital care were readmitted at three months. No significant difference was found in mortality between the groups at three months (9% versus 8%).ConclusionsHospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease.     

Relation between private health insurance and high rates of caesarean section in Chile: qualitative and quantitative study

ObjectivesTo explore the circumstances and factors that explain the association between private health insurance cover and a high rate of caesarean sections in Chile.DesignQualitative analysis of audiotaped in-depth interviews with obstetricians and pregnant women; quantitative analysis of data from face to face semistructured interview survey conducted postnatally (with women who had given birth in the previous 24-72 hours), and of a review of medical notes at a public hospital, a university hospital, and a private clinic.SettingSantiago, Chile.ParticipantsQualitative arm: 22 obstetricians, 21 pregnant women; quantitative arm: 540 postnatal women.ResultsPrivate health insurance cover requires the primary maternity care provider to be an obstetrician. In the postnatal survey, women with private obstetricians showed consistently higher rates of caesarean section (range 57-83%) than those cared for by midwives or doctors on duty in public or university hospitals (range 27-28%). Only a minority of women receiving private care reported that they had wanted this method of delivery (range 6-32%). With the diversification in the healthcare market, most obstetricians now have demanding peripatetic work schedules. Private maternity patients are a lucrative source of income. The obstetrician is committed to attend these private births in person, and the “programming” (or scheduling) of births is a common time management strategy. The rate of elective caesarean sections was 30-68% in women with private obstetricians and 12-14% in women not attended by private obstetricians.ConclusionsPolicies on healthcare financing can influence maternity care management and outcomes in unforeseen ways. The prevailing business ethos in health care encourages such pragmatism among those doctors who do not have a moral objection to non-medical caesarean section.     

Cross sectional study of reporting of epileptic seizures to general practitioners

ObjectiveComparison of reporting of recent epileptic seizures by patients to a doctor and anonymously.DesignCross sectional study of patients with epilepsy by comparison of paired questionnaires.SettingRural and urban general practices in Norfolk. Participants122 patients aged over 16 years and able to self complete a questionnaire who were recruited by 31 general practitioners when attending for review of their epilepsy.Results18 patients failed to report a seizure in the past year to their general practitioner (uncontrolled epilepsy). 40% (24/60) of people with epilepsy who anonymously reported a seizure in the past year held a driving licence, but only six revealed this to their general practitioner. The unemployment rate was 34%, substantially higher than the 9% in the general population. Measures of anxiety, depression, and stigmatisation were higher in patients with uncontrolled epilepsy.ConclusionsA significant proportion of patients with epilepsy underreport their seizures. Recognition of underreporting is important if patients are to benefit from adequate and appropriate treatment. General practitioners'' ability to treat epilepsy is hampered by their role in regulating the rights of epileptic patients to hold a driving licence or access certain occupations.

Key messages

• People with epilepsy may be reluctant to report seizures to their general practitioners as epilepsy affects their eligibility for a driving licence and access to various employment and leisure activities
• In this study about a sixth of patients anonymously reported seizures in the past year which they had not revealed to their general practitioner
• 40% of patients who anonymously reported a seizure in the past year held a driving licence, but only a quarter of these admitted this to their general practitioner
• People who had had seizures in the past year were significantly more depressed and felt more stigmatised than those who had not had a seizure
• Underreporting of seizures has important consequences for treatment, and doctors need to put more effort into explaining this to patients