Pharmacotherapy of LAMA/LABA inhaled therapy combinations for chronic obstructive pulmonary disease: a clinical overview.

INTRODUCTION: Long-acting muscarinic receptor antagonist (LAMA)/ß2-agonist (LABA) combinations represent a significant improvement in the treatment of chronic obstructive pulmonary disease (COPD) due to their remarkable ability to improve lung function, dyspnea, quality of life, and exercise capacity compared to mono-components. AREAS COVERED: This article aims to report the latest information on the clinical impact of dual bronchodilation in COPD. EXPERT OPINION: The available data supports the use of inhaled LAMA/LABA FDCs in treating COPD patients, particularly those with severe or very severe disease. These combinations provide short - and long-term benefits to COPD patients without increasing the dose of the single components, which reduces the risk of adverse events while ensuring an improvement in clinical efficacy. Unfortunately, head-to-head studies comparing all exiting LABA/LAMA combinations are relatively few. Since each available LAMA/LABA combination has a unique efficacy/safety profile that must be considered for personalized COPD therapy, further randomized controlled trials and real-world studies lasting at least one year are needed to assess what differences, if any, there are in terms of clinical outcomes when dual LAMA/LABA inhalers are compared to LAMA or LABA single inhalers, and to compare different LAMA/LABA FDCs.

An investigation of the pharmacological applications used for the Ancient Egyptian systemic model 'ra-ib' compared with modern Traditional Chinese Medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Ancient Egyptian texts only offer glimpses into their conceptual understandings of the inner-body and illness manifestation. Explanations of how prescribed materia medica were believed to work are rare and obscure, often resulting in modern approximations for ancient terminology such as 'ra-ib'-an ancient Egyptian classification predominantly translated as 'stomach'-leading to misunderstandings of historical texts, and therefore their use of pharmacology. AIM OF THE STUDY: To investigate the ra-ib and the explanatory models of illness from the Egyptian perspective, and to explore the link between these and the prescribed selection of materia medica. To then compare the conceptual mechanics of these treatment strategies with those of another non-Western tradition-namely Traditional Chinese Medicine (TCM)-to provide further insight into potential conceptual frameworks. MATERIALS AND METHODS: We conducted a case study of a unit of Ancient Egyptian texts focusing on the ra-ib. Totalling 34 prescriptions, the first stage lexicographically analysed the texts using cognitive linguistic and translation theories to produce our new understanding. This enabled our comparison of the mechanics of materia medica usage within these texts with those found in TCM outlined by the Pharmacopoeia of the Peoples Republic of Pharmacopeia of the People's Republic of China 2015 for the relevant ingredients. RESULTS: the study demonstrated that-rather than denoting the organ 'stomach'-ra-ib instead constitutes a system running from the mouth, downward to the anus. This is best translated as 'inner thoroughfare', and changes the way in which we attempt to understand potential motivations in the selection of ingredients. By exploring common themes in the use of eleven securely translated ingredients from the Egyptian corpus and the Pharmacopoeia of the People's Republic of China-representing a modern traditional system which understands the body via a series of interconnected systems-we were able to highlight certain themes which might be 'universal' to system-based traditions; this provided new insights into the Egyptian motivations for treatment selection. CONCLUSIONS: Having gained the ancient view of the body and illness, cultural comparisons are important for providing further potential insights and clarifications of a discontinued historical healing tradition. The new understanding of the ra-ib from our study greatly changes the way in which we understand the dynamics of Egyptian ethnopharmacological source material from this period.

Preoperative assessment of splenic involvement in patients with peritoneal carcinomatosis with CT and MR imaging.

PURPOSE: To estimate the performances of computed tomography (CT) and magnetic resonance imaging (MRI) and those of the combination of CT with MRI in the identification of splenic involvement in patients with peritoneal carcinomatosis (PC). MATERIAL AND METHOD: CT and MRI examinations of 26 patients with PC with splenic involvement and 26 patients with PC and no splenic involvement treated by total cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) were reviewed. There were 32 women and 20 men with a mean age of 53.44 ± 12.22 (SD) years (range: 20-73 years). Imaging examinations were reviewed separately as three independent imaging sets (CT only, MRI only and CT with MRI) by two independent readers. A consensus was reached during a joint reading session and these results were used for determining the performances of the three imaging sets in the diagnosis of splenic involvement using surgical and histopathological findings as standard of reference. RESULTS: Splenic involvement was histologically proven in 26/52 patients (50%). There were no significant differences in sensitivity, specificity and accuracy for the diagnosis of splenic involvement between CT, MRI and CT + MRI, with respectively 84.62%, 96.15% and 90.00% for CT, 84.62%, 84.62% and 85.00% for MRI and 92.31%, 92.31% and 92.00% for CT + MRI. CONCLUSION: CT and MRI have similar sensitivities, specificites and accuracies for the diagnosis of splenic involvement in patients with PC. The combination of CT and MRI does not significantly improve the preoperative diagnosis of splenic involvement in patients with PC compared to CT only.

A comparison study between lycobetaine-loaded nanoemulsion and liposome using nRGD as therapeutic adjuvant for lung cancer therapy.

To achieve tumor-selective drug delivery, various nanocarriers have been explored using either passive or active targeting strategies. Despite the great number of studies published annually in the field, only nanocarriers using approved excipients reach the clinical stage. In our study, two classic nanoscale formulations, nanoemulsion (NE) and liposome (Lipo) were selected for the encapsulation of lycobetaine (LBT). To improve the lipid solubility of LBT, oleic acid (OA) was used to complex (LBT-OA) with lycobetaine (LBT). Besides, PEGylated lecithin was used to enhance the circulation time. The release behaviors of LBT from non-PEGylated and PEGylated NE and Lipo were compared. PEGylated LBT-OA loaded Lipo (LBT-OA-PEG-Lipo) exhibited a sustained release rate pattern, and in vivo pharmacokinetic profiles showed the extended circulation compared nanoemlusions. Besides, LBT-OA-PEG-Lipo showed an enhanced anti-tumor effect in the mice xenograft lung carcinoma model. Moreover, a multi-target peptide nRGD was co-administered as a therapeutic adjuvant with LBT-OA loaded formulations, which demonstrated improved tumor penetration and enhanced extravasation of formulations. Also, co-administration of nRGD significantly improved the in vivo antitumor efficacy of different formulations, likely due to the depletion of tumor-associated macrophages (TAMs). Thus, LBT-OA-PEG-Lipo+nRGD may represent a promising strategy for cancer chemotherapy against lung carcinoma.

Traditional Chinese and Thai medicine in a comparative perspective.

The work presented in this paper compares traditional Chinese medicine and traditional Thai medicine, expounding on origins, academic thinking, theoretical system, diagnostic method and modern development. Based on a secondary analysis of available literature, the paper concentrates on two crucial historical developments: (1) the response to, and consequences of, the impact of the Western medicine; and (2) the revival of traditional medicine in these two countries and its prospects. From a comparative perspective, the analysis has led to the conclusion that the rise and fall of traditional medicine is an issue closely related with social and political issues; and the development of traditional medicines requires national policy and financial support from governments, human resource development, the improvement of service quality, and the dissemination of traditional medicine knowledge to the public. In addition, this paper also suggests deepening exchanges and cooperation between China and Thailand, strengthening cooperation between traditional medicine and medical tourism.

Searching for the origins of musicality across species.

In the introduction to this theme issue, Honing et al. suggest that the origins of musicality--the capacity that makes it possible for us to perceive, appreciate and produce music--can be pursued productively by searching for components of musicality in other species. Recent studies have highlighted that the behavioural relevance of stimuli to animals and the relation of experimental procedures to their natural behaviour can have a large impact on the type of results that can be obtained for a given species. Through reviewing laboratory findings on animal auditory perception and behaviour, as well as relevant findings on natural behaviour, we provide evidence that both traditional laboratory studies and studies relating to natural behaviour are needed to answer the problem of musicality. Traditional laboratory studies use synthetic stimuli that provide more control than more naturalistic studies, and are in many ways suitable to test the perceptual abilities of animals. However, naturalistic studies are essential to inform us as to what might constitute relevant stimuli and parameters to test with laboratory studies, or why we may or may not expect certain stimulus manipulations to be relevant. These two approaches are both vital in the comparative study of musicality.

[Comparison of European therapies for cannabis addiction among adolescents]. / Comparaison de thérapies européennes pour adolescents présentant une addiction au cannabis.

BACKGROUND: In European countries, cannabis abuse and dependence among adolescents has become a public health priority. Since 2002, studies have shown that persons seeking treatment for cannabis use are increasing. Over the past ten years, the involvement of many structures working on this topic has permitted an expansion and a diversification of treatment protocols. Moreover, international scientific studies, mainly conducted in the United States, have demonstrated the effectiveness of therapies based on motivation interviews, cognitive behavioral therapy (CBT) and family approach. Among these treatments, the multi-dimensional family therapy (MDFT), developed by the team of Professor Liddle in Miami, showed great efficiency in young adolescents with cannabis abuse problems. Five European countries therefore decided to build a randomized control study (RCT) comparing MDFT to the treatments that were commonly used. For the purpose of the research, the usual treatments had to be described and were named treatment as usual (TAU). Besides the obvious interest of implementing MDFT in Europe, it seems equally important to highlight the investment that has been made by all the European structures. The goal of this article is to describe and share the previous experience of all centers that have participated in the INCANT trial including the Netherlands, Germany, Belgium, Switzerland and France in the field of cannabis adolescent abusers. METHODOLOGY: To describe and compare European treatment as usual (TAU), we visited each structure to meet and to interview the teams regarding their practices. To perform these interviews, we used a semi directive questionnaire we had built previously. We completed the therapist's interviews with their written clinical protocol (when they had one) and a video/audiotaped session or written session. Data collection took place in five addiction centers: Therapy laden in Germany, Phoenix foundation in Switzerland, Cannabis clinic in Belgium, Palm Huis in Holland and Emergence and CEDAT in France. RESULTS: In terms of monitoring arrangements, there are many similarities between the European TAU. Indeed, all European centers were practicing individual therapy mainly focusing on the adolescent, and therapists were involving parents. In almost all European countries, the teenager was seen at one session per week, the parents were seen once a month and the duration of the therapy was about 6 months. The interview analysis has revealed that between countries, despite therapeutic techniques and differences in psychopathological approach, a global care process remained quite common. The therapeutic process, in all countries, was organized in two phases: build the therapeutic alliance and assess the situation with the adolescent, and help to coach him/her to enhance changes. DISCUSSION/CONCLUSION: The comparison of the TAU highlights the difficulties to see differences between models of psychotherapies. Are the psychotherapies really different or is it just a matter of the therapists, experience and good will? The debate is open and articles have shown arguments for both hypotheses. The analysis of our TAU indeed shows a common base, but as therapists started to formalize what they usually do, differences appear. The Incant study, in which TAU was compared to a formalized family therapy, clearly indicates differences between therapies, but only with heavy cases. Perhaps the more cases became complicated, the more there's a need for formalization and of course this will lead to differences between models.

Research gaps in psoriasis: opportunities for future studies.

Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.

Evaluating midwifery units (EMU): lessons from the pilot study.

OBJECTIVE: this paper describes the pilot study that was undertaken to test the feasibility of the recruitment plan designed to recruit women who booked to give birth in two freestanding midwifery units in NSW, Australia. The pilot preceded the full prospective cohort study, Evaluating Midwifery Units (EMU), which aimed to examine the antenatal, birth and postnatal outcomes of women planning to give birth in freestanding midwifery units compared to those booked to give birth in tertiary level maternity units in Australia and New Zealand. DESIGN: a prospective cohort study with two mutually-exclusive cohorts. SETTING: two freestanding midwifery units in NSW and their corresponding tertiary referral hospitals. PARTICIPANTS: a total of 146 women with few identified risk factors recruited between 13 September 2009 and 31 March 2010 whose planned place of birth was either a freestanding midwifery unit or tertiary maternity unit. MEASUREMENTS AND FINDINGS: the pilot study identified the feasibility of relying on the booking midwife to recruit eligible women from several antenatal booking clinics to the study. Low rates of eligible women were invited resulting in a lower than expected consent rate. In addition, although mostly only low-risk women were invited to participate, some women requiring medical consultation at the time of booking were inadvertently recruited into the study. The results of this pilot study led us to revise the study protocol to find ways of including the outcomes of all women without identified risk factors who booked at either the freestanding midwifery units or the tertiary referral hospital in that area. This paper describes the revisions that were made to the study plan. KEY CONCLUSIONS: five lessons were learned from the pilot study. We found that recruitment protocols employed for the cohort study were too complicated and required simplification to maximise the potential of the study. The study protocol needed to be changed for the main study to ensure a larger sample size and to ensure the risk profile of each cohort was as similar as possible. Sources of data needed to be expanded to produce a complete data set. IMPLICATIONS FOR PRACTICE: pilot studies are extremely useful tools in testing methods to inform research protocols. We found that the first months spent undertaking a pilot study ensured a stronger design with the potential to show more meaningful results.

Treatment in Kenyan rural health facilities: projected drug costs using the WHO-UNICEF integrated management of childhood illness (IMCI) guidelines.

Guidelines for the integrated management of childhood illness (IMCI) in peripheral health facilities have been developed by WHO and UNICEF to improve the recognition and treatment of common causes of childhood death. To evaluate the impact of the guidelines on treatment costs, we compared the cost of drugs actually prescribed to a sample of 747 sick children aged 2-59 months in rural health facilities in western Kenya with the cost of drugs had the children been managed using the IMCI guidelines. The average cost of drugs actually prescribed per child was US$ 0.44 (1996 US$). Antibiotics were the most costly component, with phenoxymethylpenicillin syrup accounting for 59% of the cost of all the drugs prescribed. Of the 295 prescriptions for phenoxymethylpenicillin syrup, 223 (76%) were for treatment of colds or cough. The cost of drugs that would have been prescribed had the same children been managed with the IMCI guidelines ranged from US$ 0.16 per patient (based on a formulary of larger-dose tablets and a home remedy for cough) to US$ 0.39 per patient (based on a formulary of syrups or paediatric-dose tablets and a commercial cough preparation). Treatment of coughs and colds with antibiotics is not recommended in the Kenyan or in the IMCI guidelines. Compliance with existing treatment guidelines for the management of acute respiratory infections would have halved the cost of the drugs prescribed. The estimated cost of the drugs needed to treat children using the IMCI guidelines was less than the cost of the drugs actually prescribed, but varied considerably depending on the dosage forms and whether a commercial cough preparation was used.

PIP: This study evaluated the impact of the integrated management guidelines of childhood illness (IMCI) developed by the WHO and UN Children's Fund on the treatment cost in Kenya. To determine the impact of the guidelines, a comparison was made of the cost of drugs actually prescribed to 747 sick children aged 2-59 months in rural facilities with the treatment cost had the children been managed following the IMCI guidelines. The study found that the estimated cost of drugs required to treat children following the IMCI guidelines was lower than the cost of the drugs actually prescribed in ill children. The average cost of drugs actually prescribed for every sick child was US$0.44. Antibiotics were the most expensive component, with phenoxymethylpenicillin syrup responsible for 59% of the total cost of prescribed drugs. The cost of medications that would have been prescribed had the children been treated using the guidelines ranges from US$0.16 to US$0.39 per patient. Managing cough and colds with antibiotics is not recommended in the IMCI guidelines, thus, compliance to guidelines would have reduced the treatment cost to one half the cost of drugs actually prescribed.

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

PIP: A randomized, double-blind, controlled trial was conducted to compare the efficacy of calcium, vitamin D, and a combination of both in the treatment of nutritional rickets among Nigerian children. Subjects included 123 Nigerian children with the deformity characteristics of rickets. For each child who was enrolled, a parent or guardian was asked to recruit a control child with the same sex, age, weight, and who had no clinical signs of rickets. Children with rickets were under treatment for 24 weeks with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of both. Then the serum calcium and alkaline phosphates were measured and a 10-point radiographic score was used to assess the response to the 24-week treatment. The results revealed a low dietary calcium intake in children with rickets and in control children. Children under vitamin D treatment appeared to have a small increase in the mean serum calcium concentration when compared to children under calcium treatment or a combination of both vitamin D and calcium. A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphates concentration of 350 U/liter or less and radiographic evidence of nearly complete healing of rickets. Overall, compliance ranged from 92% to 96% across the three groups. Since Nigerian children with rickets had low calcium intake, treatment should focus on dietary supplementation with calcium or a combination of calcium and vitamin D.

Traditional birth attendants' advice toward breast-feeding, immunization and oral rehydration among mothers in rural Bangladesh.

Traditional birth attendants (TBAs) are regarded as essential child health care providers in Bangladesh. A community-based cross-sectional study was completed using questionnaires and interviews to compare trained and untrained TBAs' advice on (1) breast-feeding, (2) immunizations and (3) oral rehydration therapy as an extended part of their maternity care training. Twenty-eight trained TBAs (TTBAs) and 27 corresponding untrained TBAs (UTBAs) in the Dhaka district were interviewed to investigate the effect of their advice on the three outcome variables of maternal health care. Additionally, 276 questionnaires were distributed to the mothers cared for by these TBAs to determine their knowledge of infant-care practices. In-depth interviews with 25 mothers provided additional insight. While TTBAs may have more knowledge and be more willing to disseminate health care information to mothers with new infants than UTBAs, the mother's health practices were independent of the advice provided by the two groups of TBAs. Additionally, the mother's health practices equaled or exceeded expected norms.

PIP: A cross-sectional study conducted in rural Bangladesh's Dhaka District compared the appropriateness and accuracy of advice given by 28 trained and 27 untrained traditional birth attendants (TBAs) on breast-feeding, immunization, and oral rehydration. In addition, perceptions of care provided by trained and untrained TBAs were analyzed through a questionnaire administered to 276 clients of these TBAs. TBAs in both groups tended to be poor, married, Islamic women with no formal education. Although the trained TBAs provided more accurate information than their untrained counterparts in terms of breast-feeding, colostrum, and when to introduce solid foods, mothers' breast-feeding knowledge and practices were unrelated to whether they had been cared for by a trained or untrained TBA. Similarly, while trained TBAs provided more correct information on both immunization and oral rehydration therapy, mothers' adherence to immunization schedules and use of rehydration when their child had diarrhea were not affected by the type of TBA who provided care. Both groups of TBAs reported providing more information to mothers about these three issues than mothers reported receiving from the TBAs. In general, maternal health practices met or exceeded expected norms.

A randomized trial of the effect of moistening misoprostol before vaginal administration when used with methotrexate for abortion.

A prospective multicenter, randomized trial was performed to evaluate if moistened misoprostol results in a more rapid abortion and a higher rate of complete abortion compared with dry misoprostol when administered intravaginally for medical abortion after methotrexate. A total of 240 pregnant women < or = 49 days gestation seeking elective abortion received 50 mg/m2 methotrexate intramuscularly followed 5-6 days later by 800 micrograms misoprostol vaginally. The misoprostol dose was repeated in 1-2 days if the abortion did not occur. Group 1 moistened the misoprostol before administration and group 2 used dry tablets. There was no statistically significant difference in the cumulative rate of abortion after the first misoprostol dose (73.0% vs 71.3%, p = 0.87), second misoprostol dose (84.1% vs 81.1%, p = 0.65), or by 35 days after methotrexate administration (95.2% vs 91.8%, p = 0.40) between groups 1 and 2, respectively. The proportion of subjects with embryonic cardiac activity 2 weeks after methotrexate injection was greater in group 2 (5.7%, 95% confidence interval [CI] 1.0%, 9.9%) than in group 1 (2.4%, 95% CI 0%, 5.0%), although not statistically significant (p = 0.21). The immediate success rate in Pittsburgh was greater, albeit not statistically, for the women that moistened the misoprostol (87% vs 76%, p = 0.19); these rates were also not statistically different in Havana (82% vs 86%, p = 0.62). The rate of side effects after methotrexate was not different between groups but women in group 1 had significantly more diarrhea (36% vs 21%, p = 0.02) and fever/warmth/chills (44% vs 30%, p = 0.04). Moistening misoprostol before vaginal administration in a medical abortion regimen with methotrexate does not statistically improve efficacy. This trial demonstrates the importance of prospective, randomized studies to prove the relative efficacy of any medical abortion treatment regimen.

PIP: A randomized trial conducted in the US and Cuba assessed whether moistening misoprostol in advance of vaginal insertion enhances the efficacy of medical abortion after methotrexate administration. 240 abortion seekers from Pittsburgh, Pennsylvania (US), and Havana, Cuba, with pregnancies of 49 days' gestation or less were randomized either to dip the four 200-mcg misoprostol tablets in water before administration (group 1) or to insert the tablets dry (group 2). The misoprostol dose was repeated in 1-2 days if abortion did not occur. There were no statistically significant differences between groups 1 and 2 in the cumulative rate of abortion after the first misoprostol dose (73.0% vs. 71.3%), after the second misoprostol dose (84.1% vs. 81.1%), or by 35 days after methotrexate administration (95.2% vs. 91.8%). The proportion of women with a continuing pregnancy, defined as the presence of embryonic cardiac activity 2 weeks after methotrexate injection, was slightly but nonsignificantly higher in group 2 (5.7%) than in group 1 (2.4%). The immediate success rate in Pittsburgh was greater, although not significantly, for women who moistened the misoprostol (87% vs. 76%); in Havana, the opposite trend was observed (82% vs. 86%). Cramping began a mean of 2.8 hours after the first misoprostol administration in group 1 and a mean of 3.5 hours later in group 2. Women in group 1 had significantly more diarrhea (36% vs. 21%) and fever/chills (44% vs. 30%) than those in group 2, but rates of nausea, vomiting, dizziness, and headache did not differ. These findings suggest that moistening misoprostol before vaginal application does not significantly improve the efficacy of methotrexate abortion.

Comparative Study between Gastro g rafin Enema and Air Enema CT: Evaluation of the Diagnostic Accuracy of Lesion Detection and Staging of Colorectal Cancer

PURPOSE: We compared the use of diluted gastrografin enema- and air enema CT for the evaluation of the diagnostic accuracy of preoperative lesion detection and the staging of colorectal carcinoma. MATERIALS AND METHODS: Forty-two patients (43 lesions) with colorectal carcinoma, diagnosed by barium enema and/or colonoscopy, underwent preoperative diluted (2.5%) gastrografin enema CT, and in another 26 patients (27 lesions) with colorectal carcinoma, air enema CT was performed. The presence or absence of lesion, its spread (T), and peritumoral lymph node (N) were analyzed. All patients underwent surgery and pathologic confirmation was obtained. RESULTS: Gastrografin enema CT and air enema CT demonstrated the primary tumor in 97.7% (42 of 43) and 96.3% of cases (26 of 27), respectively. A comparison of gastrografin enema CT and the pathologic results showed that the disease was correctly staged as T2 in five of six cases, as T3 in 28 of 31, and as T4 in two of five. Using air enema CT, the disease was correctly staged as T2 in three of three cases, as T3 in 17 of 21, and as T4 in one of two. Overall, carcinoma was correctly staged by gastrografin enema CT in 83% of cases (35 of 42) and by air enema CT in 81% (21 of 26). Nodal involvement was accurately detected in 64% of cases (27 of 42) using gastrografin enema CT and in 69% (18 of 26) using air enema CT. CONCLUSIONS: These findings suggest that the use of gastrografin enema or air enema CT does not significantly affect the diagnostic outcome.

Comparative Study between Gastro g rafin Enema and Air Enema CT: Evaluation of the Diagnostic Accuracy of Lesion Detection and Staging of Colorectal Cancer

PURPOSE: We compared the use of diluted gastrografin enema- and air enema CT for the evaluation of the diagnostic accuracy of preoperative lesion detection and the staging of colorectal carcinoma. MATERIALS AND METHODS: Forty-two patients (43 lesions) with colorectal carcinoma, diagnosed by barium enema and/or colonoscopy, underwent preoperative diluted (2.5%) gastrografin enema CT, and in another 26 patients (27 lesions) with colorectal carcinoma, air enema CT was performed. The presence or absence of lesion, its spread (T), and peritumoral lymph node (N) were analyzed. All patients underwent surgery and pathologic confirmation was obtained. RESULTS: Gastrografin enema CT and air enema CT demonstrated the primary tumor in 97.7% (42 of 43) and 96.3% of cases (26 of 27), respectively. A comparison of gastrografin enema CT and the pathologic results showed that the disease was correctly staged as T2 in five of six cases, as T3 in 28 of 31, and as T4 in two of five. Using air enema CT, the disease was correctly staged as T2 in three of three cases, as T3 in 17 of 21, and as T4 in one of two. Overall, carcinoma was correctly staged by gastrografin enema CT in 83% of cases (35 of 42) and by air enema CT in 81% (21 of 26). Nodal involvement was accurately detected in 64% of cases (27 of 42) using gastrografin enema CT and in 69% (18 of 26) using air enema CT. CONCLUSIONS: These findings suggest that the use of gastrografin enema or air enema CT does not significantly affect the diagnostic outcome.

Health policy research is essential, but difficult.

PIP: Comparative Studies on Health Sector Reform have conducted three workshops in 1999. Two of them were held in Indonesia and Mexico which focused on analyzing results, developing writing skill, and writing articles for publication in international scientific peer-reviewed journals. The third one was held in the Philippines, which focused on refining the research questions, and selecting and developing appropriate research methods and tools. Several lessons can be learned from the workshops: 1) the critical role of research in health sector reform; 2) a call for multidisciplinary researchers for the development of health policy research; 3) health reform initiatives are often politically and ideologically determined with ill-defined objectives; 4) insufficient national information systems that are of little use in studying the trends and magnitude of the phenomenon; and 5) the holistic nature of most policy research requires application of a diverse range of quantitative and qualitative methods taken from the epidemiology.^ieng

A randomized, community trial of intensive sexually transmitted disease control for AIDS prevention, Rakai, Uganda.

OBJECTIVE: To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence. STUDY DESIGN: Randomized, controlled, community-based trial in Rakai District, Uganda. METHODS: In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services. RESULTS: In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis. CONCLUSIONS: Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.

PIP: An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

The association of oral contraceptive use with plasma 25-hydroxyvitamin D levels.

OBJECTIVE: This analysis was conducted to compare wintertime 25-hydroxyvitamin D (25OHD) levels of young women who did and did not use oral contraceptives (OC). METHODS: The subjects were 66 Caucasian women aged 20 through 40 recruited from the Boston area. Plasma 25OHD was measured in February or March and again 1 year later. Other measurements included height, weight and vitamin D intake from diet and supplements. RESULTS: The initial mean 25OHD level of the 26 OC users was 41% higher than those of nonusers before adjustment for age and vitamin D intake (83 +/- 40 (sd) nmol/L compared with 59 +/- 22), and 39% higher after adjustment (p = 0.003). Five women who discontinued OC use during the year following their initial measurement all had decreases in their 25OHD levels (mean change was -25.5 +/- 17.7 (SD) nmol/L), whereas levels in women whose OC use or non-use was constant did not change. CONCLUSION: OC use increases circulating levels of 25OHD, and should be considered when interpreting values obtained for clinical evaluation or nutrition research.

PIP: This study was conducted to compare wintertime hyroxyvitamin D (250HD) levels among 66 young Caucasian women between ages 20 and 40 years from the Boston area who did and did not take oral contraceptives (OCs). Plasma 250HD was measured within a 2-month period and again after 1 year. Other measurements taken were height, weight, and intake of vitamin D from diet and supplements. The study demonstrated that the 250 HD levels of women who use OCs were as much as 24.1 nmol/l higher than those of non-OC users. This 41% difference decreased to 39% after adjustment for age and intake of vitamin D. All 5 women who discontinued OC use in the year after their initial measurement had reduced 250HD levels, while levels in the women whose OC use or non-use was constant remained unchanged throughout the study period. There were no significant associations between 250HD levels and ethinyl estradiol dosage, type of OC, or duration of use. In conclusion, OC use increases the circulating levels of 250HD of premenopausal adult women and should be taken into consideration when interpreting values obtained for clinical evaluation or nutrition research.

Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand.

Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.

PIP: Pentoxifylline, an inhibitor of tumor necrosis factor, was evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria admitted to the Bangkok (Thailand) Hospital for Tropical Diseases, in a 5-month period in 1994. All patients had 1 or more clinical manifestations of severe malaria, including cerebral malaria (n = 18), renal failure requiring dialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). Patients were randomly assigned to receive treatment for 72 hours with a combination of intravenously administered artesunate and either placebo (n = 15), low-dose (0.83 mg/kg/hour) pentoxifylline (n = 15), or high-dose (1.67 mg/kg/hour) pentoxifylline (n = 15). Overall severity was comparable in all 3 groups. Concentrations of tumor necrosis factor were reduced in all 3 groups 48 hours after treatment. There were no significant differences between groups in terms of parasite and fever clearance time, recovery time from coma in patients with cerebral malaria, duration of intubation in patients with respiratory distress, number of hemodialysis treatments required for patients with acute renal failure, or number of units of blood administered to patients in need of transfusion. These findings suggest that the addition of pentoxifylline to artesunate therapy for severe malaria produces no evident clinical benefit.

Contraception during lactation: a comparison of methods.

PIP: A comparative study was conducted on nursing mothers using various contraceptives: 120 used Norplant; 117 used the progestogen-only pill (Lynestrenol, 0.5 mg daily); 187 used the progesterone vaginal ring; and 122 used the copper IUD. The contraceptives were begun at 57 days postpartum; those using the pill or vaginal ring were advised to change methods after weaning. The 256 controls were women with similar characteristics who used lactational infertility. Follow-up visits at maternal and child health clinics occurred frequently; mother and child were examined, and histories included feeding and bleeding patterns, and any symptom or side-effect. Supplementary feeding began after 6 months. Only 2 pregnancies occurred (in the pill group) in the women using contraceptive methods; 48 of the control group became pregnant at the end of the year. 26 women gave up their vaginal rings because of use-related problems. More than 50% of the contraception group bled in the first month; 26% of controls did. Women in the progesterone group had 1-5 months more amenorrhea than controls and those with the copper IUD. There were few cases of prolonged bleeding.^ieng