Sally Hargreaves

Increase in primary liver cancer in the UK, 1979–94

1 McCarthy M. Bio-engineered tissues move towards the clinic. Lancet 1996; 348: 466. 2 Meszaros L. Manufactured living tissue helps heal venous ulcers. Dermatol Times 1995; July: 15. 3 Eaglstein WH, Iriondo M, Laszlo K. A composite skin substitute for surgical wounds: a clinical experience. J Derm Surg 1995; 21: 1–5. 4 Mechcatie E. FDA expedites review of synthetic skins. Skin and Allergy News 1995; Aug: 4.

Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis.

Introduction:Since 2002, the WHO has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy. These two drugs are known to have differing toxicity profiles, but the risk of these toxicities overall is not well established. Methods:We systematically reviewed adverse events among treatment-naive HIV-positive adults and children receiving either NVP or EFV as part of first-line antiretroviral therapy. The primary outcome was drug discontinuation as a result of any adverse event; specific toxicities were evaluated as secondary outcomes. Point estimates and 95% confidence intervals (95% CIs) were calculated and proportions and odds ratios (ORs) pooled using fixed-effects meta-analysis. Results:We reviewed data on 26 446 adults and 3975 children from eight randomized trials and 26 prospective cohorts. Overall, adults on NVP were more than two times more likely to discontinue treatment due to any adverse event compared to patients on EFV (OR 2.2, 95% CI 1.9–2.6). Severe hepatotoxicity (OR 3.3, 95% CI 2.5–4.2), severe skin toxicity (OR 3.9, 95% CI 2.5–5.4), and severe hypersensitivity reactions (OR 2.4, 95% CI 1.9–2.9) were more likely to occur among patients on NVP. Patients receiving EFV were more likely to experience severe central nervous system events (OR 3.4, 95% CI 2.1–5.4). Similar associations were seen in children. Discussion:Compared to NVP, EFV is associated with a lower frequency of severe adverse events, in particular treatment discontinuations. This finding supports a move toward EFV-based therapy as the preferred first-line treatment regimen for HIV treatment within a public health approach.

Scale-up of Routine Viral Load Testing in Resource-Poor Settings: Current and Future Implementation Challenges

Cost and complexity have hindered implementation to date of viral load testing in resource-limited settings. If rapid and timely scale-up is to become a reality, numerous factors will need to be addressed, including health and laboratory system strengthening, pricing, and multiple programmatic and funding challenges.

Time to right the wrongs: improving basic health care in Nigeria.

Nigeria, once heralded as the beacon of Africa, has fallen somewhat short of this potential. Years of kleptocratic repressive dictators and military rule, coupled with widespread corruption, have resulted in large-scale neglect and deterioration of public services. Nowhere is this more apparent than within the health sector. Government-run health-care services barely function: half the population are unvaccinated for routine diseases, and a burgeoning epidemic of HIV/AIDS, only now being adequately addressed, leaves 3.5 million already infected and without access to the most basic of care. A poorly structured health service that relies on vertical programmes for HIV, tuberculosis, and malaria, means that coordination is chaotic, and already scant resources fail to reach the lower levels in which they are needed most. I visited Nigeria in October, 2001, with Médecins Sans Frontières, a humanitarian aid organisation that has been working in Nigeria since 1996. I witnessed the poor level of health care in Nigeria for myself--a country that is more than capable of providing effective services--and concluded that, even now, political priorities are being put ahead of the populations basic needs. The challenges to the new civilian government are monumental, and it is yet to show any solid commitment to improving the health of Africas biggest nation.

Mortality after Fluid Bolus in Children with Shock Due to Sepsis or Severe Infection: A Systematic Review and Meta-Analysis

Introduction Sepsis is one of the leading causes of childhood mortality, yet controversy surrounds the current treatment approach. We conducted a systematic review to assess the evidence base for fluid resuscitation in the treatment of children with shock due to sepsis or severe infection. Methods We searched 3 databases for randomized trials, quasi-randomized trials, and controlled before-after studies assessing children with septic shock in which at least one group was treated with bolus fluids. The primary outcome was mortality at 48 hours. Assessment of methodological quality followed the GRADE criteria. Relative risks (RRs) and 95% confidence intervals (CI) were calculated and data pooled using fixed-effects method. Results 13 studies met our inclusion criteria. No bolus has significantly better mortality outcomes at 48 hours for children with general septic shock (RR 0.69; 95%CI 0.54–0.89), and children with malaria (RR 0.64; 95%CI 0.45–0.91) when compared to giving any bolus. This result is largely driven by a single, high quality trial (the FEAST trial). There is no evidence investigating bolus vs no bolus in children with Dengue fever or severe malnutrition. Colloid and crystalloid boluses were found to have similar effects on mortality across all sub-groups (general septic shock, malaria, Dengue fever, and severe malnutrition). Conclusions The majority of all randomized evidence to date comes from the FEAST trial, which found that fluid boluses were harmful compared to no bolus. Simple algorithms are needed to support health-care providers in the triage of patients to determine who could potentially be harmed by the provision of bolus fluids, and who will benefit.

Engaging new migrants in infectious disease screening: a qualitative semi-structured interview study of UK migrant community health-care leads.

Migration to Europe - and in particular the UK - has risen dramatically in the past decades, with implications for public health services. Migrants have increased vulnerability to infectious diseases (70% of TB cases and 60% HIV cases are in migrants) and face multiple barriers to healthcare. There is currently considerable debate as to the optimum approach to infectious disease screening in this often hard-to-reach group, and an urgent need for innovative approaches. Little research has focused on the specific experience of new migrants, nor sought their views on ways forward. We undertook a qualitative semi-structured interview study of migrant community health-care leads representing dominant new migrant groups in London, UK, to explore their views around barriers to screening, acceptability of screening, and innovative approaches to screening for four key diseases (HIV, TB, hepatitis B, and hepatitis C). Participants unanimously agreed that current screening models are not perceived to be widely accessible to new migrant communities. Dominant barriers that discourage uptake of screening include disease-related stigma present in their own communities and services being perceived as non-migrant friendly. New migrants are likely to be disproportionately affected by these barriers, with implications for health status. Screening is certainly acceptable to new migrants, however, services need to be developed to become more community-based, proactive, and to work more closely with community organisations; findings that mirror the views of migrants and health-care providers in Europe and internationally. Awareness raising about the benefits of screening within new migrant communities is critical. One innovative approach proposed by participants is a community-based package of health screening combining all key diseases into one general health check-up, to lessen the associated stigma. Further research is needed to develop evidence-based community-focused screening models - drawing on models of best practice from other countries receiving high numbers of migrants.

Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis.

Introduction:The risk of adverse drug events associated with nevirapine (NVP) is suggested to be greater in pregnant women. We conducted a systematic review and meta-analysis of severe adverse events in HIV-positive women who initiated NVP while pregnant. Methods:We searched six databases for studies reporting adverse events among HIV-positive pregnant women who had received NVP-based antiretroviral therapy for at least 7 days. Data were pooled by the fixed-effects method. Results:Twenty studies (3582 pregnant women) from 14 countries were included in the final review. The pooled proportion of patients experiencing a severe hepatotoxic event was 3.2% [95% confidence interval (CI) 2.1–4.3%], severe rash was experienced by 3.3% of patients (95% CI 2.1–4.5%) and 6.1% (95% CI 3.9–8.3%) of patients discontinued NVP due to an adverse event. These results were comparable to frequencies observed in the general adult patient population, and to frequencies reported in non-pregnant women within the same cohort. For pregnant women with a CD4 cell count above 250 cells/&mgr;l there was a non-significant tendency towards an increased likelihood of severe cutaneous adverse events (OR 1.4, 95% CI 0.8–2.4) and severe hepatotoxic events (OR 1.5, 95%CI 0.9-2.3) and consequently an increased risk of toxicity-driven regimen substitution (OR 1.7, 95% CI 1.1–2.6). Discussion:These results suggest that the frequency of adverse events associated with NVP use in pregnant women, although high, is no higher than reported for NVP in the general adult population. Pregnant women with a high CD4 cell count may be at increased risk of adverse events, but evidence supporting this association is weak.

Impact on and use of an inner-city London Infectious Diseases Department by international migrants: a questionnaire survey.

BackgroundThe UK has witnessed a considerable increase in immigration in the past decade. Migrant may face barriers to accessing appropriate health care on arrival and the current focus on screening certain migrants for tuberculosis on arrival is considered inadequate. We assessed the implications for an inner-city London Infectious Diseases Department in a high migrant area.MethodsWe administered an anonymous 20-point questionnaire survey to all admitted patients during a 6 week period. Questions related to sociodemographic characteristics and clinical presentation. Analysis was by migration status (UK born vs overseas born).Results111 of 133 patients completed the survey (response rate 83.4%). 58 (52.2%) were born in the UK; 53 (47.7%) of the cohort were overseas born. Overseas-born were over-represented in comparison to Census data for this survey site (47.7% vs 33.6%; proportional difference 0.142 [95% CI 0.049–0.235]; p = 0.002): overseas born reported 33 different countries of birth, most (73.6%) of whom arrived in the UK pre-1975 and self-reported their nationality as British. A smaller number (26.4%) were new migrants to the UK (≤10 years), mostly refugees/asylum seekers. Overseas-born patients presented with a broad range and more severe spectrum of infections, differing from the UK-born population, resulting in two deaths in this group only. Presentation with a primary infection was associated with refugee/asylum status (n = 8; OR 6.35 [95% CI 1.28–31.50]; p = 0.023), being a new migrant (12; 10.62 [2.24–50.23]; p = 0.003), and being overseas born (31; 3.69 [1.67–8.18]; p = 0.001). Not having registered with a primary-care physician was associated with being overseas born, being a refugee/asylum seeker, being a new migrant, not having English as a first language, and being in the UK for ≤5 years. No significant differences were found between groups in terms of duration of illness prior to presentation or duration of hospitalisation (mean 11.74 days [SD 12.69]).ConclusionMigrants presented with a range of more severe infections, which suggests they face barriers to accessing appropriate health care and screening both on arrival and once settled through primary care services. A more organised and holistic approach to migrant health care is required.

Health-care provision for asylum seekers and refugees in the UK

Dec 31, 1992. Ethical approval was obtained along with permission from all hospitals prior to case-note review. It has been suggested that any increase in incidence of juvenile-onset Crohn’s disease may be attributed to earlier diagnosis rather than reflecting a true increase. We found that the mean length of time from symptom onset to first admission was 12·5 months for the period 1981–83 compared with 7·5 months for 1990–92. In view of this we have used date of symptom onset rather than date of diagnosis as our reference date. 349 incident cases of Crohn’s disease were identified (M/F ratio 1·3/1). All incidence rates were calculated per million population per year and the 95% CIs were estimated assuming a Poisson distribution of cases. The age and sex standardised incidence rose from 19·1 (CI 16·4–25·9) in 1981–83 to 29·1 (24–36·2) in 1990–92. The sexstandardised age-specific incidence rates are as follows: 0–6 year olds, no change between 1981 and 1992, (incidence about 8); 7–11 year olds, incidence increased from 18·3 (11·1–28·2) in 1981–83 to 25·8 (16·7–38·1) in 1990–92; 12–16 year olds, incidence doubled from 34·8 (25·4–46·4) in 1981–83 to 67·7 (51·9–86·5) in 1990–92. The crude incidence rates, calculated using date of first admission, show the same changes as seen for the standardised rates but are directly comparable with the 1969–83 data (figure). The rise in incidence between 1981–92 fits that predicted by a linear-trend analysis of this previous data, with the predicted incidence for 1990–92 being 27·3 (actual incidence 27·6). We conclude that the incidence of juvenile-onset Crohn’s disease continues to rise at the same rate in Scotland. This appears to be a true increase rather than a result of changing diagnostic patterns, and is largely due to the increase in incidence in the 12–16-years age group.

Rape as a war crime: putting policy into practice.

During the Bosnian war of 1992-95 Yugoslav women and hundreds of other Muslim women were systematically raped and tortured in a clear attempt to advance the cause of ethnic cleansing. Several of the women took to court and testified against three Bosnian soldiers in the courtrooms of the Yugoslav war-crimes tribunal in The Hague. The ruling made on the rape cases between Yugoslav women and the Bosnian Serb army is a landmark in establishing that systematic rape during conflict is not merely a violation of the practice of war but a crime against humanity. In turn sexual assault during slavery has been recognized as an independent crime under humanitarian and human rights laws. The ruling is very significant because it opens the door for many other victims of sexual violence to press for their recognition as victims for penalties and for compensation. It also means that effort will consequently be made to promote its application. However whether the codification of such laws can be translated into the practical protection of women during conflict remains to be seen.