Single or double needle insertion in twin's amniocentesis: Does the technique influence the risk of complications?

OBJECTIVE: To compare complication rates following amniocentesis in twin gestations, according to sampling technique and number of needle insertions. STUDY DESIGN: A retrospective cohort study of all women with twin gestations who underwent amniocentesis and delivered in a single university affiliated medical center during 2002-2016. Amniocentesis was performed either through one uterine entry with passage through the inter-twin membrane or through two different entries to the two amniotic sacs. Pregnancy outcome of women that underwent single needle insertion amniocentesis, was compared to this of double needle insertion. Primary outcome was neonatal complications within 4 weeks after amniocentesis (late abortion, chorioamnionitis, preterm premature rupture of membranes, or hospitalization due to related symptoms). Secondary outcomes were gestational week at delivery and labor characteristics. RESULTS: The study group comprised 212 women. Of them, 73 (34.4%) underwent a single uterine insertion and 139 (65.6%) two separate needle insertions. Baseline characteristics did not differ between the groups. The amniocentesis complication rate was 13.7% in the single insertion group and 16.5% in the double insertion group (p = 0.587). Multivariate analysis found that a single insertion method had no statistically significant influence on complication rate, after making adjustments for potential confounders (OR = 1.085, 95% CI 0.4-2.9; p = 0.871). Other labor characteristics were similar between the groups. CONCLUSION: Needle insertion technique in twin gestation amniocentesis was not associated with procedure related complications.

The economics of polypharmacology: fixed dose combinations and drug cocktails.

The history of Fixed Dose Combination (FDC) oral drug products has been tumultuous over its history. Some FDCs were prepared for marketing purposes and others for clinical improvements. Often, the products prepared for marketing advantage ended up causing negative outcomes. However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS/HIV and for oral contraceptives, just to name two examples. International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs. The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient's medication taking compliance. On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually. Overall, there is a great deal of evidence in favor of appropriate FDCs.

Payment for research participation: a coercive offer?

Payment for research participation has raised ethical concerns, especially with respect to its potential for coercion. We argue that characterising payment for research participation as coercive is misguided, because offers of benefit cannot constitute coercion. In this article we analyse the concept of coercion, refute mistaken conceptions of coercion and explain why the offer of payment for research participation is never coercive but in some cases may produce undue inducement.

Consumption and costs of antihypertensive drugs in Mexico: are diuretic agents a standing technological trajectory?

BACKGROUND: Little is known about hypertension medication consumption and costs in Mexico. Hypertension control is a pharmacological challenge and a public health issue. OBJECTIVE: (a) To compare drug sales, number of written prescriptions, and monthly treatment costs among 5 classes of antihypertensive drugs and (b) to analyze diuretic drug sales and prescriptions to determine whether these antihypertensive agents represent an established technological trajectory. METHODS: A retrospective time series data study from 1999 to 2003. Data sources used were International Marketing Services of Mexico drug sales and the Mexico Prescription Audit databases. The 5 different classes of antihypertensive drugs were accommodated into 4 main technological trajectories according to their main biological mechanisms of action. Each technological trajectory was assessed using consumption and prescription data. Daily defined dose was used to calculate drug treatment costs. RESULTS: The market for cardiovascular agents is one of the largest, and in 2003 accounted for a value market share of 59 billion US dollar and a unit share of 40.7 million. Among cardiovascular agents, antihypertensive drugs made up a large percentage of market shares. Calcium channel blockers and angiotensin-converting enzyme inhibitors I had the biggest share value of the total cardiovascular market. Amlodipine had the highest share among calcium channel blockers, and enalapril and captopril had the largest share among angiotensin-converting enzyme inhibitors I. The top-selling diuretic drug was furosemide. The trend in number of prescriptions was parallel to that in sales. The diuretic spironolactone was the most expensive drug treatment (59 US dollar). Treatment with spironolactone might represent 47% of the income of a Mexican family if their household income was close to minimum wage (124 US dollar). CONCLUSIONS: The most effective and least expensive drugs-diuretics-had the smallest market share of all antihypertensive agents in Mexico. Nevertheless, diuretic agents are still in use and kept over time a steady market share both in value and in units.

Use of sertraline, paroxetine and fluvoxamine by nursing women.

BACKGROUND: The pharmacological treatment of depression in nursing women requires information on the magnitude of medication exposure to the infant that may occur through breast milk. AIMS: To examine serum concentrations of antidepressants in infants exposed to these medications through breast-feeding. METHOD: Maternal and infant serum concentrations of sertraline, paroxetine and fluvoxamine were determined with high-performance liquid chromatography (limit of detection=1 ng/ml). RESULTS: No detectable medication was present in any infant exposed to paroxetine (n=16) or fluvoxamine (n=4). Among infants exposed to sertraline (n=30), detectable medication was present in 24% of serum samples. A significant negative correlation was found between infant age and infant serum concentration. Sertraline was significantly more likely to be detected in an infant if the mother's daily dose was 100 mg or higher. No adverse sequelae occurred in any infant. CONCLUSIONS: This study shows that paroxetine, fluvoxamine and sertraline produce minimal exposure to infants when taken by nursing mothers.

Evaluation of studies investigating the effectiveness of pharmacists' clinical services.

A quantitative evaluation of randomized trials of counseling, education, and other clinical services provided by pharmacists was performed. Data sources were MEDLINE and the bibliographies of published articles. Pharmacists' services were categorized as counseling of patients, counseling of physicians, counseling of both patients and physicians, and patient care. The outcomes extracted were measures of patient behavior, disease, symptoms, and patient knowledge. Thirty-two trials met the inclusion criteria. The pharmacists were specified as clinical pharmacists in 24 trials and as community pharmacists in 2. In six unblinded trials of patient counseling, the outcomes favored the counseled patients over control patients in every trial, and the effects were statistically significant in five trials (the outcome was medication adherence in these five trials). In seven trials of counseling of both patients and their physicians, patient outcomes were significantly better in the intervention group in six trials, four of which were single blind. Two trials in which patients were randomized to either physician counseling or control groups yielded inconsistent results. In one trial in which physicians were randomized to receive counseling from pharmacists, the proportion of prescriptions meeting guidelines was higher in the counseling group than in the control group. Four trials of patient care by pharmacists were inconclusive. These trials demonstrated that counseling of patients and their physicians by pharmacists can improve patient outcomes. The evidence that counseling of patients alone improved patient outcomes was good, though weaker because of suboptimal trial design.

Indirect cost of ischemic heart disease to employers.

BACKGROUND: The management of healthcare programs by employers requires accurate information about the indirect and direct costs of important chronic diseases. OBJECTIVE: To determine the indirect costs of ischemic heart disease from the perspective of the employer in private industry in the United States. DESIGN: Indirect cost of illness analysis using the human capital approach, taking the perspective of the employer rather than that of society. METHODS: Ischemic heart disease was identified in a proprietary claims database of 3.1 million insured persons using an algorithm based on administrative codes. Economic data were derived from the Bureau of Labor Statistics, the Employment Management Association, and published sources. Work-loss data were taken from the National Center for Health Statistics' Health Interview Survey. The indirect cost was calculated as the sum of the costs due to morbidity and mortality. From the perspective of the employer, morbidity costs come from lost productivity, idle assets, and nonwage factors resulting from absenteeism and mortality costs are expenditures for replacing and retraining workers. This differs from calculations from the societal perspective, in which indirect costs are the value of an individual's lost income--both current and potential. RESULTS: The total indirect cost of ischemic heart disease to employers in private industry was $182.74 per enrollee. Ninety-five percent of the indirect cost was the consequence of work loss due to morbidity rather than of mortality costs. CONCLUSION: From the perspective of the employer, the indirect cost of ischemic heart disease is overwhelmingly due to morbidity costs.

Characterization of the angR gene of Vibrio anguillarum: essential role in virulence.

The ability to utilize the iron bound by high-affinity iron-binding proteins in the vertebrate host is an important virulence factor for the marine fish pathogen Vibrio anguillarum. Virulence in septicemic infections is due to the presence of a highly efficient plasmid-encoded iron transport system. AngR, a 110-kDa protein component of this system, appears to play a role in both regulation of the expression of the iron transport genes fatDCBA and the production of the siderophore anguibactin. Therefore, study of the expression of the angR gene and the properties of its product, the AngR protein, may contribute to the understanding of the mechanisms of virulence of this pathogen. In this work, we present genetic and molecular evidence from transposition mutagenesis experiments and RNA analysis that angR, which maps immediately downstream of the fatA gene, is part of a polycistronic transcript that also includes the iron transport genes fatDCBA and angT, a gene located downstream of angR which showed domain homology to certain thioesterases involved in nonribosomal peptide synthesis of siderophores and antibiotics. In order to dissect the specific domains of AngR associated with regulation of iron transport gene expression, anguibactin production, and virulence, we also generated a panel of site-directed angR mutants, as well as deletion derivatives. Both virulence and anguibactin production were dramatically affected by each one of the angR modifications. In contrast to the need for an intact AngR molecule for anguibactin production and virulence, the regulation of iron transport gene expression does not require the entire AngR molecule, since truncation of the carboxy terminus carrying the nonribosomal peptide synthetase cores, as well as the site-directed mutations, resulted in derivatives that retained their ability to regulate gene expression which was only abolished after truncation of amino-terminal sequences containing helix-turn-helix and leucine zipper motifs and a specialized heterocyclization and condensation domain found in certain nonribosomal peptide synthetases. The evidence, while not rigorously eliminating the possibility that a separate regulatory polypeptide exists and is encoded somewhere within the 5'-end region of the angR gene, strongly supports the idea that AngR is a bifunctional protein and that it plays an essential role in the virulence mechanisms of V. anguillarum. We also show in this study that the angT gene, found downstream of angR, intervenes in the mechanism of anguibactin production but is not essential for virulence or iron transport gene expression.

Compliance with prescribed drugs: challenges for the elderly population.

Compliance with prescribed drug regimens is particularly important among the elderly because of their increased vulnerability and greater burden of chronic disorders. This narrative review discusses the factors that are important to compliance, with particular reference to the elderly. These factors are the patient's perceptions of his disease and it's treatment, the physician's perceptions, the manner the physician assumes and the language he uses to communicate with the patient, the patient's living situation, regular medication review, and a continuity of health care provision. Since it is the patient who decides how to use the therapy, his or her involvement in the process of explaining and understanding it is the key to improved compliance.

Images of possibility: adult and further education opportunities for people with learning difficulties.

Further education opportunities should be an integral part of community-based provision for people with mental health problems. Yet people with a history of mental health difficulties are under-represented in adult and further education, and many colleges and local education authorities have yet to develop appropriate provision, as ALISON WERTHEIMER reports.

Outcomes research: collaboration among academic researchers, managed care organizations, and pharmaceutical manufacturers.

Medical and pharmaceutical outcomes research has been of increasing interest in the past 10 to 15 years among healthcare providers, payers, and regulatory agencies. Outcomes research has become a multidisciplinary field involving clinicians, health services researchers, epidemiologists, psychometricians, statisticians, psychologists, sociologists, economists, and ethicists. Collaboration among researchers in different organizations that offer different types of services and various research expertise is the essential element for any successful outcomes project. In this article we discuss collaboration on outcomes research among academic researchers (mainly those who work in colleges of pharmacy), managed care organizations, and research-based pharmaceutical manufacturers, with a focus on the opportunities and challenges facing each party. The pharmaceutical industry needs information to make product and promotion decisions; the managed care industry has data to offer but needs analysis of these data; and pharmacy schools, among other academic institutions, have skilled researchers and data-processing capacity but require projects for revenue, research training, experience, and publications. Challenges do exist with such endeavors, but collaboration could be beneficial in satisfying the needs of the individual parties.

The AngR protein and the siderophore anguibactin positively regulate the expression of iron-transport genes in Vibrio anguillarum.

Vibrio anguillarum virulence is associated with the presence of a plasmid-mediated iron-uptake system expressed under iron-limiting conditions, which consists of the siderophore anguibactin and specific iron-transport proteins. This system is maximally expressed under iron-limiting conditions and requires the AngR protein that acts as a positive regulator of anguibactin biosynthesis and also possess an EntE-like enzymatic function that may play a role in anguibactin biosynthesis. In this work, we demonstrate that in addition to possessing these functions related to anguibactin production, AngR also positively regulated transcription of the iron-transport genes fatA and fatB. We also show that transcription of angR is repressed by Fur under iron-rich conditions. In addition, we present evidence that anguibactin itself enhanced transcription of the iron-transport genes fatA and fatB, independently of AngR and the trans-acting factor (TAF) product(s). The presence of either AngR (together with the TAF product(s)) or anguibactin alone led to a partial level of expression of the iron-transport genes fatA and fatB, while full expression is achieved when AngR, the TAF products and anguibactin are all present.

An overview of pharmacoepidemiology.

Pharmacoepidemiology is the application of epidemiological principles and methods to the study of drug effects in human populations. The goal of this discipline is to characterize, control and predict the effects and uses of pharmacological treatment modalities. Pharmacoepidemiology is also concerned with the economic impact and health benefits of unintended drug effects. The increasing importance of pharmacoepidemiology has been created by the need to develop a more accurate portrait of how drugs are used in the general population. Sophisticated and potent drug therapies require surveillance beyond the scope of the carefully controlled clinical trials of Phases I, II and III. Case-control and cohort studies, which allow scientists to evaluate the effects of patient variables on clinical outcomes, provide a wealth of information regarding the study of unexpected drug effects, drug utilization, treatment costs and the individualization of therapy.

Structural and functional analyses of mutant Fur proteins with impaired regulatory function.

Vibrio anguillarum Fur mutants, 775met9 and 775met11, were characterized. V. anguillarum 775met9 had a change of D to G at position 104 located in the carboxy terminus resulting in impaired Fur activity. Computer analysis predicts perturbation of an alpha-helix in the carboxy terminus which may interfere with Fur protein conformation. Strain 775met11 had a change in the start codon resulting in no protein synthesis. The mutants are unstable, and reversion to the wild type occurs frequently.

Characterization of the Vibrio anguillarum fur gene: role in regulation of expression of the FatA outer membrane protein and catechols.

The chromosomally encoded Vibrio anguillarum fur gene was characterized. The amino acid sequence of the Fur protein showed a very high degree of homology with those of V. cholerae and V. vulnificus. The degree of homology was lower, although still high, with the Escherichia coli and Yersinia pestis Fur amino acid sequences, while the lowest degree of homology was found with the Pseudomonas aeruginosa Fur protein. The C-terminal portion of Fur is the least conserved region among these Fur proteins. Within this portion, two regions spanning amino acids 105 to 121 and 132 to the end are the least conserved. A certain degree of variation is also present in the N termini spanning amino acids 28 to 46. Regulation of expression of the V. anguillarum fur gene by iron was not detected by immunoblot analysis. Mutations in the cloned fur gene were generated either by site-directed mutagenesis (the Lys-77 was changed to a Gly to generate the derivative FurG77) or by insertion of a DNA fragment harboring the aph gene in the same position. FurG77 was impaired in its ability to regulate a reporter gene with the Fur box in its promoter, while the insertion mutant was completely inactive. V. anguillarum fur mutants were obtained by isolating manganese-resistant derivatives. In one of these mutants, which encoded a Fur protein with an apparent lower molecular weight, the regulation of the production of catechols and synthesis of the outer membrane protein FatA were partially lost. In the case of another mutant, no protein was detected by anti-Fur serum. This derivative showed a total lack of regulation of biosynthesis of catechols and FatA protein by iron.