Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

Cash transfers to enhance completion of TB screening among household contacts in rural Tanzania.

Tanzanian TB guidelines recommend facility-based TB screening for symptomatic household contacts (HHCs) or those aged <5 years, but cost remains a major barrier. In this study, we evaluate the use of unconditional cash transfers (UCTs) to facilitate completion of HHC TB screening.In this prospective interventional study, we enrolled index people diagnosed with TB (PWTB) within 8 weeks of TB treatment initiation from the TB clinic at Haydom Lutheran Hospital, Haydom, Tanzania, and surrounding TB dispensaries in rural Tanzania. The study provided at the time of enrollment an UCT up to 40,000 Tanzanian shillings (USD16.91) directly to heads of households with PWTB, covered medical costs from screening activities and provided three bi-weekly phone reminders to facilitate HHC TB screening. The primary outcome was TB screening completion for all HHCs compared to the same period of the preceding year.We enrolled 120 index PWTB, including 398 HHCs between July and December 2022. The median age for index PWTB was 35 years; 38% were females. Sixty-five (54%) households completed screening for all HHCs, compared to 7% during the same period of the preceding year.These interventions may considerably improve completion of HHC TB screening in rural Tanzania..

Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis.

This review presents an overview of the available literature regarding intranasal corticosteroids (INCs) for the treatment of allergic rhinitis (AR). Various treatment options exist for AR including INCs, antihistamines and leucotriene antagonists. INCs are considered to be the most effective therapy for moderate-to-severe AR, as they are effective against nasal and ocular symptoms and improve quality of life. Their safety has been widely observed. INCs are effective and safe for short-term use. Local adverse events are observed but generally well-tolerated. The occurrence of (serious) systemic adverse events is unlikely but cannot be ruled out. There is a lack of long-term safety data. INC may cause serious eye complications. The risk of INCs on the hypothalamic-pituitary-adrenal axis, on bone mineral density reduction or osteoporosis and on growth in children, should be considered during treatment. Pharmacological characteristics of INCs (e.g. the mode of action and pharmacokinetics) are well known and described. We sought to gain insight into whether specific properties affect the efficacy and safety of INCs, including nasal particle deposition, which the administration technique affects. However, advances are lacking regarding the improved understanding of the effect of particle deposition on efficacy and safety and the effect of the administration technique. This review emphasizes the gaps in knowledge regarding this subject. Advances in research and health care are necessary to improve care for patients with AR.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

National approaches to TB care in adolescents.

BACKGROUND: Adolescents bear a large burden of TB but high-prevalence countries differ significantly in their approach to address the specific needs of adolescent patients. We explore the national approaches to TB care in adolescents and compare them to the recommendations of the WHO.METHODS: We conducted a scoping review to describe the country-level guidelines to TB care in adolescents in high-burden countries. These guidelines were obtained through open sources. Information on TB care in adolescents were extracted from guidelines and compared to WHO recommendations.RESULTS: We found a lack of consensus in defining adolescents and that many national guidelines do not address the special healthcare needs of adolescents nor align with the WHO recommendations. Recently updated country guidelines are more likely to recommend short-course regimens for TB preventive treatment and countries with a higher level of income were more likely to follow WHO guidance for microbiological confirmation of TB disease in adolescents.CONCLUSION: A clear understanding of the burden of TB in adolescents that is reflected in disaggregated data reported at the country level is imperative in order to address the specific challenges to care in this high-risk group.

Impact of Cell Culture and Copper Dose on Gene Expression in Bovine Liver.

The objectives of these experiments were to investigate (1) the relative abundance of transcripts for Cu-responsive genes in whole bovine liver vs. cultured hepatocytes and (2) the influence of Cu dose on the relative abundance of transcripts for Cu-responsive genes in cultured bovine hepatocytes. Experiment 1: Liver samples were obtained immediately post-mortem from one healthy Angus steer. Half of the tissue samples were placed in RNAlater solution; the remaining half was used to isolate hepatocytes. Experiment 2: A subset of cultured hepatocytes was incubated in media containing: 0 mg/L, 0.10 mg/L, 1.0 mg/L, 10.0 mg/L, and 100 mg/L Cu for 1 h. Transcripts analyzed were aldehyde dehydrogenase (ALDH2), apolipoprotein A-1 (APOA1), antioxidant 1 (ATOX1), ATPase copper transporting alpha (ATP7A), ATPase copper transporting beta (ATP7B), betaine homocysteine methyltransferase (BHMT), flavin reductase (BLVRB), carbonic anhydrase II (CA2), copper chaperone for superoxide dismutase (CCS), cytochrome c oxidase copper chaperone (COX17), Cu transporter 1 (CTR1), glutamate dehydrogenase (GLUD1), glutathione synthetase (GSS), protein disulfide isomerase A3 (PDIA3), and superoxide dismutase (Cu-Zn) (SOD1). Β-Actin (ACTB) was selected as the endogenous control in both experiments. Experiment 1: Whole liver had greater (P < 0.01) relative abundance of mRNA for APOA1, ATOX1, ATP7A, ATP7B, COX17, CTR1, ALDH2, BHMT, BLVRB, CA2, GLUD1, and GSS when compared with cultured hepatocytes. Experiment 2: Copper dose impacted all identified transcripts. These results indicate that the relative abundance of Cu-responsive transcripts is different in whole vs. cultured hepatocytes and that the relative abundance of Cu-responsive genes is dependent on Cu dose in cultured hepatocytes.

The Relation Between Tinnitus and a Neurovascular Conflict of the Cochleovestibular Nerve on Magnetic Resonance Imaging.

INTRODUCTION: Magnetic resonance (MR) imaging is often used in diagnostic evaluation of tinnitus patients. Incidental findings like a neurovascular conflict (NVC) in the cerebellopontine angle are often found; however, the diagnostic value of this finding remains unclear. The aim of this study is to investigate whether the type or degree of compression of the vestibulocochlear nerve is of diagnostic value in patients with a NVC. METHODS: A retrospective study was performed in 111 tinnitus patients with available MR imaging between 2013 and 2015. Clinical and audiometric variables were gathered and MR imaging was reevaluated by two neuroradiologists. NVCs were analyzed using a grading system based on previous research by Sirikci et al. RESULTS:: In total, 220 ears were available for assessment. In patients with unilateral tinnitus a loop compression and an indentation of the cochleovestibular nerve were more frequent than in patients with bilateral tinnitus. However, there was no significant difference in distribution of the type of compression between tinnitus and nontinnitus ears. Patient with unilateral tinnitus had a significantly higher degree of hearing loss in the symptomatic ear, compared with the asymptomatic ear and with the bilateral tinnitus group. Also, it was found that the degree of hearing loss did not differ between the various types of compression. CONCLUSION: This study did not find a diagnostic value of specific types of compression in patients with a NVC. Although the distribution of NVC classification was different in patients with unilateral and bilateral tinnitus, there was no definite relation between the type of NVC and the presence of ipsilateral tinnitus. Also, the degree of hearing loss was not related to specific types of NVC.

Risk Factors for Sustained Cholera Transmission, Juba County, South Sudan, 2014.

We conducted a case-control study to identify risk factors for the 2014 cholera outbreak in Juba County, South Sudan. Illness was associated with traveling or eating away from home; treating drinking water and receiving oral cholera vaccination were protective. Oral cholera vaccination should be used to complement cholera prevention efforts.

Free flap reconstruction for head and neck cancer can be safely performed in both young and elderly patients after careful patient selection.

Surgical treatment of head and neck cancer often results in complex defects requiring reconstruction with microvascular free tissue transfer. However, in elderly patients, curative treatment with radical surgery and free flap reconstruction is often withheld. The objective of this study is to assess the outcomes of free flap surgery in elderly patients, using a standard surgical complication classification system. A retrospective review was conducted of patients who underwent primary free flap reconstruction following major surgery for head and neck cancer between 1995 and 2010. Complications were assessed using the Clavien Dindo classification system, and grades III-V were classified as major complications. Comorbidity was classified according to the adult comorbidity evaluation index 27. A comparison was done between patients <70 and ≥70 years. Two hundred-two patients were included in this study. Multivariate analysis showed that only disease stage was a significant predictor of recipient site complications, and comorbidity was the only significant predictor of medical complications. Age was not a predictor of complications. There were no significant differences in disease specific or overall survival between young and elderly patients. Optimal patient selection for free flap surgery is essential. This requires thorough pre-operative assessment, including analysis of comorbidity in both young and elderly patients. Patients' biological age, and not chronological age, should be individually determined to assess feasibility of major surgery. Patients should not be denied surgery based on age alone.

Outbreak of pyrazinamide-monoresistant tuberculosis identified using genotype cluster and social media analysis.

SETTING: Monoresistance to pyrazinamide (PZA) has infrequently been associated with Mycobacterium tuberculosis. OBJECTIVE: To report an outbreak of PZA-monoresistant M. tuberculosis in Virginia involving two genotype clusters from December 2004 to August 2010. RESULTS: Thirty cases were identified involving a predominantly young, US-born population with histories of substance use and incarceration and a large proportion of children aged <15 years (n= 6, 20%); of these, 23 cases (77%) were culture-confirmed as M. tuberculosis complex. DNA fingerprinting and molecular analysis of the PZA resistance gene, pncA, demonstrated a clonal strain that was not M. bovis. Genotypic data provided the initial link between seemingly unrelated cases, and helped reveal a historic genotype cluster of cases from 2004. Further genotype cluster and contact investigation procedures, including the novel use of the social networking website Facebook.com, revealed additional links between the 2004 and 2009 genotype clusters and described an ongoing, extensive outbreak necessitating an enhanced screening and treatment protocol for contacts. CONCLUSIONS: This outbreak demonstrates how tuberculosis can spread through a young, vulnerable population. The use of genotypic data and the novel incorporation of social media investigations were critical to understanding the settings and context of infectivity.

Relation between age, comorbidity, and complications in patients undergoing major surgery for head and neck cancer.

BACKGROUND: Multiple factors have been identified as predictors of complication after head and neck surgery. However, little is known about the exact role of different comorbid conditions in the development of postoperative complications. This question is especially interesting in the elderly population. The aim of this study was to investigate the association between comorbidity and types of postoperative complications with special attention to age differences. METHODS: A retrospective analysis was performed of 1,201 major surgical interventions for head and neck malignancies in a tertiary referral center between 1995 and 2010. The Adult Comorbidity Evaluation 27 (ACE-27) index was used to analyze severity (mild, moderate, and severe comorbidity) and type (12 different organ systems) of comorbidity. The Clavien-Dindo index was used to evaluate grade and type of complications after treatment. RESULTS: In univariate analysis gender, comorbidity, stage, mandibulectomy, total laryngectomy, neck dissection, and length of surgery significantly predicted grade of complication. In a multivariate analysis, complication was predicted by age, stage, length of surgery, and various comorbidities. After specification of the complications, age was only a predictor of medical complications; tumor stage was a significant factor in surgical complications. Length of surgery was the only significant variable in all types of complications. CONCLUSIONS: Specific comorbidities are associated with specific complications; however, age itself seems not to be a contraindication for major head and neck surgery. With careful preoperative assessment and risk analysis, physicians can better individualize treatment recommendations.

Predictors of postoperative complications and survival in patients with major salivary glands malignancies: a study highlighting the influence of age.

BACKGROUND: The purpose of this study was to reveal prognostic factors for surgical complications and survival in young and elderly patients with malignant salivary gland tumors. METHODS: Retrospective analysis of surgically treated patients with malignant major salivary gland tumors was performed. Of the 111 patients, 33 patients were 70 years or older and 78 patients were under 70. Comorbidity was recorded using the Adult Comorbidity Evaluation-27 index and complications using the Clavien-Dindo classification. RESULTS: Comorbidity and complications were significantly more frequent in elderly patients (p < .05). Age, comorbidity, and length of surgery were not significant independent predictors of complications. Stage was the only independent predictive factor for postoperative complications and disease-specific survival. CONCLUSION: Based on this retrospective analysis reviewing surgically treated patients, age alone should not be a reason to treat elderly patients differently, as it was not a predictor of either complications or disease-specific survival.

Comorbidity, complications, and survival of sinonasal malignancies in young and elderly treated by surgery.

OBJECTIVE: Sinonasal malignancies are uncommon neoplasms with several histological subtypes, most commonly treated with surgery and postoperative radiotherapy. The aim of this study was to evaluate complications and survival, focusing on differences between elderly and younger patients undergoing surgery. STUDY DESIGN: Historical cohort based on medical records. SETTING: Tertial referral center. SUBJECTS AND METHODS: Medical charts of 103 surgically treated patients (71 patients younger than 70 years and 32 patients aged 70 years and older) in a tertiary referral center with sinonasal malignancy were retrospectively analyzed. Comorbidity was scored according to the Adult Comorbidity Evaluation 27 system. Treatment outcomes were analyzed by collecting treatment-related complications scores and survival data. RESULTS: Although comorbidity was more common in elderly patients, no significant differences were recorded in complications. In multivariate analysis, length of surgery was the only predictor for complication. Furthermore, no significant differences were seen in disease-specific survival and recurrence in young and elderly patients. Young patients with malignant epithelial tumors and melanoma had worse overall survival than patients with other histological subtypes. However, in elderly patients, no significant differences were seen in survival between histological subtypes. CONCLUSION: For complications, survival, and recurrence, no differences were seen between young and elderly patients. Based on this study, surgery can also be safely performed in elderly sinonasal cancer patients after careful preoperative evaluation and patient selection.

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.

Diagnostic value of CT and MRI in the detection of paratracheal lymph node metastasis.

The presence of paratracheal lymph node (PTLN) metastasis harbours a worse prognosis. Uniform guidelines on PTLN dissection are missing, mainly because of the value of diagnostic techniques for the detection of PTLN metastasis are not clear. This study is performed to identify CT and MRI criteria for detection of PTLN metastasis. 149 patients who underwent laryngectomy and a PTLN dissection between 1990 and 2010 were included. Patient, tumour, treatment and follow up data were collected. On computed tomography (CT) and magnetic resonance imaging (MRI) different test criteria were examined. Considering PTLN with a maximal axial diameter of ≥5 mm as positive predicts PTLN metastasis best: sensitivity and specificity 70% and 36% (CT) and 50% and 71% (MRI). Other risk factors for PTLN metastasis were subglottic extension of the tumour (sensitivity is 45%) and clinical positive neck status (sensitivity is 59%). When at least one of these risk factors was present and the status of PTLN was considered positive, a high sensitivity (90% for CT and 100% for MRI) and a lower specificity (19% for CT and 32% for MRI) was found. If at least one of the risk factors such as subglottic extension, clinical positive neck and PTLN with a maximal axial diameter of ≥5 mm is present, sensitivity and negative predictive value for the prediction of PTLN metastasis are high, but the specificity is low. These risk factors can be used to select laryngectomy patients for PTLN dissection.

Co-morbidity and treatment outcomes of elderly pharyngeal cancer patients: a matched control study.

Treatment choice in elderly pharyngeal cancer patient is disputed. This study was aimed to asses association of co-morbidity, complications and survival in different treatment modalities of pharyngeal cancer patients. Retrospective analysis of pharyngeal cancer patients, diagnosed between 1997 and 2007 in a tertiary referral hospital was performed. Patients 75years and older (n=42), were matched with two control patients 64years and younger (n=84). Co-morbidity (ACE-27), treatment related complications and survival data were assessed and analyzed. Frequency of co-morbidity was similar in both age groups, although discarding alcohol abuse resulted in higher incidence of co-morbidity in the elderly group. Complication rate was not significantly different. In a multivariate analysis only stage found to be a significant predictor of complications. Survival estimates adjusted to sex, age and birth cohort revealed co-morbidity to be a significant predictor for survival in elderly and young patients. No evidence has been found to treat elderly pharyngeal cancer patients differently than younger ones. Treatment related complications are not predicted by co-morbidities in young and elderly patients; however survival is predicted by comorbidity. Therefore thorough pre-treatment evaluation and care necessary in the elderly population.

The impact of comorbidity on treatment-related side effects in older patients with laryngeal cancer.

The standard treatment of elderly head and neck patients is controversial. The goal of this study was to evaluate the relationship between co-morbidity and complications in elderly laryngeal cancer patients treated with different modalities. Retrospective analysis of patients 75 years old and older with laryngeal cancer (n=139) and patients 65 years old and younger as a reference control group (n=289) diagnosed in our department between 1997 and 2007 has been performed. Pretreatment co-morbidity (ACE-27), treatment-related complications and one- and six-month death rates have been analyzed. Co-morbidity rate was more pronounced in the elderly group, but did not result in more complications. Correlation has been found between co-morbidity and complication in the whole patients group, but not in the elderly group. By multivariate analysis, in all age groups radiation therapy (vs. total laryngectomy) and tumor stage were predictors of complications but co-morbidity and age were not. According to our study there is no reason to treat elderly laryngeal cancer patients differently. The weaker relation between co-morbidity and complications emphasizes the importance of careful pre-treatment evaluation in elderly.

Extensively drug-resistant tuberculosis in children with human immunodeficiency virus in rural South Africa.

SETTING: Extensively drug-resistant tuberculosis (XDR-TB) has been documented worldwide, but reports of XDR-TB in children are extremely limited. OBJECTIVE: To report the characteristics of pediatric XDR-TB patients in rural South Africa. DESIGN: We retrospectively reviewed children with sputum culture-confirmed XDR-TB from Tugela Ferry, South Africa, from January 2006 to December 2007. Demographic, clinical and microbiologic data were abstracted from medical records. RESULTS: Four children aged 6-8 years with XDR-TB were reviewed. Two had previous histories of TB. All were human immunodeficiency virus (HIV) infected orphans; three received highly active antiretroviral therapy (HAART) before XDR-TB diagnosis. All had clinical and radiographic improvement and sputum culture conversion while on standardized XDR-TB treatment and HAART. Two tolerated concomitant XDR-TB and HIV treatment well. Two experienced neuropsychiatric side effects related to cycloserine. All have survived >24 months and all were cured. Prior to XDR-TB diagnosis, the children had resided in the hospital's pediatric ward for a median of 8 months (range 5-17), including a 3-month overlapping period. CONCLUSIONS: XDR-TB is a microbiologic diagnosis that, even with HIV co-infection, can be successfully identified. Concurrent XDR-TB and HIV therapy is feasible and effective in children, although more research is needed into potential overlapping toxicities. Nosocomial transmission is suggested, calling for infection control policies in pediatric wards.

Maternal deaths from anaesthesia. An extract from Why mothers die 1997-1999, the Confidential Enquiries into Maternal Deaths in the United Kingdom.

This article is reprinted from Why Mothers Die 1997-1999, the fifth report of the Confidential Enquiries into Maternal Deaths in the United Kingdom.