Cost-effectiveness of different strategies to manage patients with sciatica

The aim of this paper is to estimate the relative cost-effectiveness of treatment regimens for managing patients with sciatica. A deterministic model structure was constructed based on information from the findings from a systematic review of clinical effectiveness and cost-effectiveness, published sources of unit costs, and expert opinion. The assumption was that patients presenting with sciatica would be managed through one of 3 pathways (primary care, stepped approach, immediate referral to surgery). Results were expressed as incremental cost per patient with symptoms successfully resolved. Analysis also included incremental cost per utility gained over a 12-month period. One-way sensitivity analyses were used to address uncertainty. The model demonstrated that none of the strategies resulted in 100% success. For initial treatments, the most successful regime in the first pathway was nonopioids, with a probability of success of 0.613. In the second pathway, the most successful strategy was nonopioids, followed by biological agents, followed by epidural/nerve block and disk surgery, with a probability of success of 0.996. Pathway 3 (immediate surgery) was not cost-effective. Sensitivity analyses identified that the use of the highest cost estimates results in a similar overall picture. While the estimates of cost per quality-adjusted life year are higher, the economic model demonstrated that stepped approaches based on initial treatment with nonopioids are likely to represent the most cost-effective regimens for the treatment of sciatica. However, development of alternative economic modelling approaches is required.     

Prevalence of Symptoms of Gastroesopahgeal Reflux in a Cohort of Saudi Arabians: A Study of 1265 Subjects

Background/Aims:

In this study, we aimed to determine the prevalence of gastroesophageal reflux disease (GERD) in the general population of the capital city of Riyadh and to assess its association with other factors including age, smoking, body mass index (BMI), asthma, as well as the presence of other co-morbid diseases.

Materials and Methods:

We used the Gastroesophageal Reflux Disease Questionnaire (GerdQ) for diagnosing GERD, based on a GerdQ score of 8 or more. Riyadh was divided into four quadrants, and from each area, a single shopping mall was chosen randomly to conduct our surveys. Data collected included age, sex, history of smoking, history of asthma or any other medical condition, dietary habits, monthly household income, history and frequency of heartburn, epigastric pain, regurgitation of food, nausea, sleep disturbance from heartburn, the use of common over-the-counter antacids for the control of their symptoms, and their height and weight.

Results:

Over a 4-week period from the 19 December 2012 to 17 January 2013, a total of 1265 individuals were included in the survey. The mean age was 29.97 ± 11.58 years. Females formed 67.81% of the respondents and 62.73% had one or more episodes of heartburn per week. Based on a cutoff GERDQ score of 8, the prevalence of GERD in the surveyed population was 45.4%. GERD was more prevalent in older individuals (mean age 31.9 vs. 30.0 years, P < 0.001) and in those with a higher BMI (27.29 vs. 26.31 kg/m², P = 0.02). There was no difference between males (45.43%) and females (45.13%) (P = 0.92); there was a trend of a higher prevalence in smokers (51.63% vs. 44.41%), but it did not reach statistical significance (P = 0.09).

Conclusion:

Symptoms suggestive of GERD as determined by the translated GerdQ are prevalent among this study population.     

Endocrinology: Ovarian response in consecutive cycles of ovarian stimulation in normally ovulating women

Ovarian stimulation combined with intra-uterine insemination(IUI) is an effective treatment of non-tubal infertility butmost women undergo several cycles of treatment to achieve apregnancy. This prospective study was designed to assess theconsistency (or variation) of ovarian responses and the effectof various ovarian stimulation protocols on this consistencyin consecutive cycles of ovarian stimulation and IUI in womenwith non-ovulatory infertility. A total of 86 regularly menstruatingovulating patients each completed three to six cycles of ovarianstimulation and IUI (n = 347 cycles). Ovarian stimulation wasachieved by sequential clomiphene citrate/human menopausal gonadotrophin(HMG), HMG-only or combined gonadotrophin-releasing hormoneanalogue—HMG protocols in 33, 29 and 24 patients respectively,and each patient used the same protocol consistently throughoutthe study. Standard methods were used to monitor ovarian responseand to perform IUI. Using each patient as her own control, repeatedmeasurements analysis of variance revealed consistency of ovarianresponse in consecutive ovarian stimulation cycles, as shownby the number and mean diameter of maturing pre-ovulatory follicles,peak plasma oestradiol, duration of stimulation and mean HMGrequirements. This consistency existed using any of the ovarianstimulation protocols. We conclude that regularly menstruatingand ovulating women are likely to have similar ovarian responsesin consecutive cycles of ovarian stimulation and IUI if thesame ovarian stimulation protocol is used consistently. Thisis expected to reduce the frequency of treatment monitoringand clinic visits and to help schedule the timing of IUI.     

Synergistic killing of gram-negative bacilli by cefotaxime, its desacetyl metabolite and human polymorphonuclear neutrophils

Using an in-vitro model the effects of sub-MIC cefotaxime and its desacetyl metabolite singly and in combination on killing of E. coli by PMNs were studied. Our purpose was to determine if the parent compound and its metabolite had a synergistic effect on killing of E. coli by PMNs. Thymidine-labelled serum resistant Escherichia coli 018:K1:H7 were incubated during log phase growth with varying sub-MICs (1/2, 1/8, 1/32) of cefotaxime, its desacetyl metabolite and both agents together, or phosphate buffered saline (PBS) as a control for 90 min at 37 degrees C. The bacteria were then washed and a series of opsonization experiments was performed using intact and sonicated PMNs. Killing of bacteria was determined at 3, 10 and 20 min. Uptake and killing of bacteria by PMNs were measured using standard techniques. Pre-treatment of E. coli with cefotaxime alone and desacetyl cefotaxime and cefotaxime together resulted in significantly enhanced bacterial killing by PMNs at all three exposure times to PMNs. Pre-treatment of the bacteria with sub-MICs of desacetyl cefotaxime alone showed enhanced killing only after exposure for three minutes. In all cases, any increased killing was independent of ingestion by the phagocytes. The opsonization experiments demonstrated that contact between bacteria and PMNs was necessary for optimal killing to occur. The enhanced killing of the sub-MIC antibiotic pre-treated bacteria was seen even when sonicated PMNs were used. The extent of bacterial killing, however, was less than that seen with intact PMNs.     

Derivation of primary sequences and secondary structures of rev responsive element from HIV-1 infected mothers and infants following vertical transmission

We have characterized the primary RRE sequences of HIV-1, including in vivo genetic variation and functional motifs required for Rev-RRE interactions as well as evaluated the RNA secondary structures of RRE derived from five mother-infant pairs following vertical transmission. Multiple (157) RRE sequences derived from mother-infant pairs showed that primary nucleotide sequences of RRE were highly conserved with a low degree of viral heterogeneity following vertical transmission. We found that the RRE sequences from mothers and infants folded and retained all the essential stem-loop formation required for Rev-RRE interactions. More importantly, a primary 9-nucleotide (5'-CACTATGGG-3') RRE sequence in the stem-loop B that is required for optimal Rev recognition and must be presented as a stem-bulge-stem structure was highly conserved in most of the sequences. The domains required for RRE-host protein interactions were also conserved in most of the RRE sequences. Taken together, the primary RRE sequences in the context of secondary structures were maintained and the Rev-RRE interaction domains were conserved following vertical transmission, which is consistent with a crucial role of RRE in HIV-1 pathogenesis.     

The potential of cord blood stem cells for use in regenerative medicine

It is estimated that up to 128 million individuals might benefit from regenerative medicine therapy, or almost 1 in 3 individuals in the US. If accurate, the need to relieve suffering and reduce healthcare costs is an enormous motivator to rapidly bring stem cell therapies to the clinic. Unfortunately, embryonic stem (ES) cell therapies are limited at present by ethical and political constraints and, most importantly, by significant biologic hurdles. Thus, for the foreseeable future, the march of regenerative medicine to the clinic will depend on the development of non-ES cell therapies. At present, non-ES cells easily available in large numbers can be found in the bone marrow, adipose tissue and umbilical cord blood (CB). Each of these stem cells is being used to treat a variety of diseases. This review shows that CB contains multiple populations of pluripotent stem cells, and can be considered the best alternative to ES cells. CB stem cells are capable of giving rise to hematopoietic, epithelial, endothelial and neural tissues both in vitro and in vivo. Thus, CB stem cells are amenable to treat a wide variety of diseases including cardiovascular, ophthalmic, orthopedic, neurologic and endocrine diseases.