Diagnostic accuracy of physician review, expert algorithms and data-derived algorithms in adult verbal autopsies

BACKGROUND: The verbal autopsy (VA) is used to collect information on cause-specific mortality from bereaved relatives. A cause of death may be assigned by physician review of the questionnaires, or by an algorithm. We compared the diagnostic accuracy of physician review, an expert algorithm, and data-derived algorithms. METHODS: Data were drawn from a multicentre validation study of 796 adult deaths that occurred in hospitals in Tanzania, Ethiopia, and Ghana. A 'gold standard' cause of death was assigned using hospital records and death certificates. The VA interviews were carried out by trained fieldworkers 1-21 months after the subject's death. A cause of death was assigned by physician review and an expert algorithm. Data-derived algorithms that most accurately estimated the cause-specific mortality fraction (CSMF) for each cause of death were identified using logistic regression. RESULTS: The most common causes of death were tuberculosis/AIDS (CSMF = 18.6%), malaria (CSMF = 10.7%), meningitis (CSMF = 8.3%), and cardiovascular disorders (CSMF = 8.2%). The CSMF obtained using physician review was within +/-20% of the gold standard value for 12 causes of death including the four common causes. The CSMF obtained using the expert algorithm was within +/-20% of the gold standard for eight causes of death, including tuberculosis/AIDS, malaria, and meningitis. The CSMF obtained using the data-derived algorithms was within +/-20% of the gold standard for seven causes of death, including tuberculosis/ AIDS, meningitis, and cardiovascular disorders. All three methods yielded a specificity of at least 80% for all causes of death, and a sensitivity of at least 80% for deaths due to injuries and rabies. CONCLUSIONS: For those settings where physician review is not feasible, expert and data-derived algorithms provide an alternative approach for assigning many causes of death. We recommend that the algorithms proposed herein are validated further.     

Investigation of under-ascertainment in epidemiological studies based in general practice

BACKGROUND: One of the aims of the Study of Infectious Intestinal Disease (IID) in England is to estimate the incidence of IID presenting to general practice. This sub-study aims to estimate and correct the degree of under-ascertainment in the national study. METHODS: Cases of presumed IID which presented to general practice in the national study had been ascertained by their GP. In 26 general practices, cases with computerized diagnoses suggestive of IID were identified retrospectively. Cases which fulfilled the case definition of IID and should have been ascertained to the coordinating centre but were not, represented the under-ascertainment. Logistic regression modelling was used to identify independent factors which influenced under-ascertainment. RESULTS: The records of 2021 patients were examined, 1514 were eligible and should have been ascertained but only 974 (64%) were. There was variation in ascertainment between the practices (30% to 93%). Patient-related factors independently associated with ascertainment were: i) vomiting only as opposed to diarrhoea with and without vomiting (OR 0.37) and ii) consultation in the surgery as opposed to at home (OR 2.18). Practice-related factors independently associated with ascertainment were: i) participation in the enumeration study component (OR 1.78), ii) a larger number of partners (OR 0.3 for 7-8 partners); iii) rural location (OR 2.27) and iv) previous research experience (OR 1.92). Predicted ascertainment percentages were calculated according to practice characteristics. CONCLUSION: Under-ascertainment of IID was substantial (36%) and non-random and had to be corrected. Practice characteristics influencing variation in ascertainment were identified and a multivariate model developed to identify adjustment factors which could be applied to individual practices. Researchers need to be aware of factors which influence ascertainment in acute epidemiological studies based in general practice.     

Postnatal depression and infant growth and development in low income countries: a cohort study from Goa, India.

BACKGROUND: Postnatal depression is a recognised cause of delayed cognitive development in infants in developed countries. Being underweight is common in South Asia. AIMS: To determine whether postnatal depression contributes to poor growth and development outcomes in Goa, India. METHODS: Cohort study for growth outcomes with nested case-control study for developmental outcomes. A total of 171 babies were weighed and measured at 6-8 weeks following birth. The following measures were used: Edinburgh Postnatal Depression Scale for maternal mood, and sociodemographic and infant health variables. Outcome measures were: weight (<5th centile), length (<5th centile), and Developmental Assessment Scale for Indian Infants scores at six months. RESULTS: Postnatal depression was a strong, and independent, predictor of low weight and length and was significantly associated with adverse mental development quotient scores. CONCLUSIONS: This study provides evidence for the first time that postnatal depression, a potentially treatable disorder, is a cause of poor growth and development in South Asia.     

Soy protein isolate reduces the oxidizability of LDL and the generation of oxidized LDL autoantibodies in rabbits with diet-induced atherosclerosis

The incidence of atherosclerosis can be modified by diet, and plant-derived proteins have a beneficial effect, but the underlying mechanisms remain unclear. It has been suggested that oxidized LDL (oxLDL) and autoantibodies against oxLDL are important in the development of atherosclerosis. We analyzed these factors in rabbits fed a nonpurified diet supplemented with high cholesterol (10.0 g/kg) containing either 270.0 g/kg casein (CAS, n = 10) or 270.0 g/kg soy protein isolate (SPI, n = 10) for 2 mo. Plasma and purified serum LDL from rabbits were analyzed at d 0, 15, 30, 45 and 60 of treatment, and the size of atherosclerotic lesions was evaluated at d 60 of treatment. CAS-fed rabbits had significantly higher plasma cholesterol at d 15-45 and LDL cholesterol levels at d 15 and 30. Levels of trilinolein and phosphatidylcholine hydroperoxides were higher in the LDL fraction of rabbits fed CAS than in those fed SPI. Also, CAS-fed rabbits had higher levels of highly oxidized LDL [monoclonal antibody (mAb) 24-reactive oxLDL] in plasma at d 60, whereas SPI-fed rabbits had higher levels of minimally oxidized LDL (mAb 28-reactive oxLDL) at d 45. These results were consistent with the earlier formation of anti-oxLDL antibodies and the presence of a larger area of atherosclerotic lesion in rabbits fed the CAS diet. These data indicate the importance of both the type of dietary protein used in the induction of atherosclerosis and the relevance of immunologic mechanisms in addition to biochemical and physiologic factors in the pathogenesis of atherosclerosis.     

Induction of CYP1A in the beagle dog by an inhibitor of kinase insert domain-containing receptor: differential effects in vitro and in vivo on mRNA and functional activity.

Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A.     

The use of the female condom by women in Brazil participating in HIV prevention education sessions.

OBJECTIVES: To study HIV-positive women and women at risk of becoming infected with HIV who attended HIV prevention education group sessions at a university hospital in Brazil and to compare the use of the female condom and the male condom by these two groups of women. METHODS: The study subjects were 165 women participating in HIV prevention education group sessions at the Medical School Hospital of Ribeir?o Preto of the University of S?o Paulo, in the city of Ribeir?o Preto, S?o Paulo, Brazil. Women could be enrolled in the study from August 2000 to June 2001, and the follow-up observation time period was from August 2000 to July 2001. Male condoms and female condoms were freely distributed to all the participants at the end of each educational session and also at the end of each follow-up visit that the participants made. Each woman took part in an initial interview and was asked to return monthly. At each follow-up visit an additional short interview was carried out in order to investigate use of the male condom and of the female condom. Variables that were examined for the study included age, education, ethnic group, marital or relationship status, number of children, the women's use of male condoms and female condoms, commercial sex (whether the women had ever had sex in exchange for money, gifts, or favors), and previous knowledge of the female condom. RESULTS: The 165 women studied fell into the following three categories: 132 of them (80.0%) were HIV-positive, 26 of them (15.8%) had a sexually transmitted disease (STD) other than HIV and did not have an HIV-positive partner, and 7 of them (4.2%) had an HIV-positive partner but did not have HIV or any other STD. The women ranged in age from 15 to 64 years, with a mean of 30.3 years. Of the women in the study, 69.7% of them were married or were cohabitating, and 90.9% of them had a sexual partner. Just over two-thirds of the women had seven years of formal schooling or less. Out of 163 women, a total of 31 of them (19.0%) had never used the male condom with a partner, and 49 of the 163 (30.1%) had not used a male condom at the time of the last sexual intercourse. Out of the 165 women, 74 of them (44.8%) returned for at least one follow-up visit. Of these 74 women, 58 of them (78.3%) reported using the female condom between the initial interview and the first follow-up visit. The majority of the 74 women who returned for a visit liked using the female condom, and the women reported that their partners also generally accepted the female condom. In comparison to women at risk of HIV, HIV-positive women were more likely to have used the male condom with a partner before the initial interview. Women who continued returning over a longer follow-up period were more likely to have used the female condom at the time of the last sexual intercourse. No association was found between female condom use at the time of last sexual intercourse and the woman's HIV infection status. CONCLUSIONS: In comparison to the women at risk of HIV, the HIV-positive women in our study were more likely to use male condoms with their partners, to return for follow-up visits, and to have a longer follow-up period. The acceptance of the female condom among the HIV-positive women in this study, as reported at their first follow-up visit, appears to be similar to the acceptance of the female condom among women in general in Brazil.     

Characteristics of Contraceptive Use in Sao Paulo State, Brazil

Objective To know the characteristics of contraceptive use in Sao Paulo State collected by the Demographic and Health Survey （DHS） conducted in 1996. Methods Data of Sao Paulo in 1996 were analyzed compared with the previous DHS carried on in 1986focusing on Sao Paulo State. Contraceptive use among married or cohabiting women by age, number of children and schooling was closely examined. Age and timing of female sterilization were also analyzed. Results The results showed that unlike Brazil there was a stability of female sterilization in Sao Paulo State during 1986 and 1996. There was a pattern in Sao Paulo： up to 30 years old the pill was the most used contraceptive, after 30 there was a predominance of female sterilization, which increased with the number of children and decreased with schooling. The use of male methods had also increased in the 1986 and 1996 period, being greater in Sao Paulo than in Brazil. Sao Paulo also presented more diversity in the use of reversible contraceptives. Conclusions The predominant two contraceptive methods in Brazil and Sao Paulo changed from 1986 to 1996, i.e..from pill to female sterilization.     

Two molecular forms of gonadotropin-releasing hormone (GnRH-I and GnRH-II) are expressed by two separate populations of cells in the rhesus macaque hypothalamus

Gonadotropin-releasing hormone represents the primary neuroendocrine link between the brain and the reproductive axis, and at least two distinct molecular forms of this decapeptide (GnRH-I and GnRH-II) are known to be expressed in the forebrain of rhesus macaques (Macaca mulatta). Although the distribution pattern of the two corresponding mRNAs is largely dissimilar, their expression appears to show some overlap in specific regions of the hypothalamus; this raises the possibility that some cells express both molecular forms of GnRH. To resolve this issue, double-label histochemistry was performed on hypothalamic sections from six male rhesus macaques, using a monoclonal antibody to GnRH-I and a riboprobe to monkey GnRH-II mRNA. In total, more than 2000 GnRH neurons were examined but in no instance were GnRH-I peptide and GnRH-II mRNA found to be coexpressed. This finding emphasizes that GnRH-I and GnRH-II are synthesized by two distinct populations of hypothalamic neurons, and suggests that they may be regulated by different neuroendocrine pathways.     

Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in mice

L-Arginine (L-Arg), a substrate for nitric oxide synthase (NOS) at a dose of 250-500 mg/kg, i.p., significantly reduced the duration of immobility both in the forced swimming test (FST) and in the tail suspension test (TST), two models of depression in mice, without changing locomotion in an open field. Paradoxically, a similar effect was observed with the administration of N(G)-nitro-L-arginine (L-NNA) (0.3-10 mg/kg, i.p.), an inhibitor of NOS. However, higher doses of L-Arg (750-1000 mg/kg) and L-NNA (30 mg/kg) did not produce any anti-immobility effect in FST and TST. The inactive isomers D-Arg (100-1000 mg/kg, i.p.) and D-NNA (0.3-30 mg/kg, i.p.) did not affect immobility duration in either the FST and TST. Preadministration of L-NNA (30 mg/kg, i.p.), but not of D-NNA completely blocked the anti-immobility effect of L-Arg (500 mg/kg, i.p.) in the FST. Similarly, L-Arg (750 mg/kg, i.p.), but not D-Arg blocked the anti-immobility effect of L-NNA (3 mg/kg, i.p.) in the FST. The results indicate that either the synthesis of NO or the inhibition of its synthesis may produce antidepressant-like effects when assessed in the FST and TST. The physiological meaning of this finding is still obscure, but it could indicate that NO has a dual role in the modulation of depression.