Individual Observation Period Research Articles

Snow Depth and Air Temperature Seasonality on Sea Ice Derived From Snow Buoy Measurements

Snow depth on sea ice is an essential state variable of the polar climate system and yet one of the least known and most difficult to characterize parameters of the Arctic and Antarctic sea ice systems. Here, we present a new type of autonomous platform to measure snow depth, air temperature, and barometric pressure on drifting Arctic and Antarctic sea ice. “Snow Buoys” are designed to withstand the harshest environmental conditions and to deliver high and consistent data quality with minimal impact on the surface. Our current dataset consists of 79 time series (47 Arctic, 32 Antarctic) since 2013, many of which cover entire seasonal cycles and with individual observation periods of up to 3 years. In addition to a detailed introduction of the platform itself, we describe the processing of the publicly available (near real time) data and discuss limitations. First scientific results reveal characteristic regional differences in the annual cycle of snow depth: in the Weddell Sea, annual net snow accumulation ranged from 0.2 to 0.9 m (mean 0.34 m) with some regions accumulating snow in all months. On Arctic sea ice, the seasonal cycle was more pronounced, showing accumulation from synoptic events mostly between August and April and maxima in autumn. Strongest ablation was observed in June and July, and consistently the entire snow cover melted during summer. Arctic air temperature measurements revealed several above-freezing temperature events in winter that likely impacted snow stratigraphy and thus preconditioned the subsequent spring snow cover. The ongoing Snow Buoy program will be the basis of many future studies and is expected to significantly advance our understanding of snow on sea ice, also providing invaluable in situ validation data for numerical simulations and remote sensing techniques.

Efficacy and safety of everolimus plus exemestane in patients with HR+, HER2− advanced breast cancer progressing on/after prior endocrine therapy in routine clinical practice: Primary results from the non-interventional study, STEPAUT

BackgroundSTEPAUT, an Austrian non-interventional study, evaluated the safety and efficacy of everolimus plus exemestane in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) recurring/progressing on/after nonsteroidal aromatase inhibitors (NSAIs) in routine clinical practice. MethodsPostmenopausal women with HR+, HER2− ABC progressing on/after NSAIs receiving everolimus plus exemestane in accordance with routine practice and the current version of Summary of Product Characteristics were eligible. Planned individual observation period corresponded to the duration of treatment until formal study end. ResultsOverall, 236 patients (median age: 65 years) were enrolled at 17 sites across Austria. The median progression-free survival (mPFS) in the overall population was 9.5 months (95% confidence interval [CI]: 8.6–10.7 months). The mPFS (95% CI) in patients who received everolimus 10 and 5 mg was 9.9 months (7.3–11.5 months) and 8 months (4.7–10.7 months), respectively. The median time to progression was numerically longer in patients who had a therapy break (11.9 months, 95% CI: 10.0–14.6 months) versus those who did not have any therapy break (10.7 months, 95% CI: 8.9–12.6 months). Patients experienced grade 1 (53.7%), grade 2 (35.9%), grade 3 (9.9%), grade 4 (0.2%) adverse events (AEs). The most common AEs of any grade were stomatitis, mucositis (53.8%), rash, exanthema (29.7%), loss of appetite, nausea (28.4%). ConclusionsReal-world safety and efficacy data from STEPAUT were consistent with results from BOLERO-2, supporting everolimus plus exemestane as a suitable treatment option for HR+, HER2− ABC recurring/progressing on/after NSAIs.

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry.

Non‐clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non‐clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first‐ and second‐line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC‐Registry), 99 patients with papillary mRCC treated with systemic first‐line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first‐line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression‐free survival from start of first‐line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow‐up, and 9% were alive at the end of the individual 3‐year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real‐world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.

Prosthodontic Treatment Outcomes in Periodontally Compromised Patients: A 6- to 20-Year Long-Term Cohort Study.

To report and analyze long-term treatment outcomes in a patient cohort with severe periodontal disease treated with an employed protocol combining use of implants and double-crown prosthetic support. A convenience sample of 16 patients with generalized severe periodontal disease were prosthodontically managed with support from 83 dental implants and 21 removable prostheses using a double-crown concept (11 implant-tooth supported and 10 implant supported). Each patient was examined 2 to 4 weeks before scheduled teeth extraction and examined again following treatment completion at the time of insertion of the superstructures. Subsequent recall examinations were performed every 3 months over a 6- to 20-year period. Predetermined clinical parameters were recorded at each session, and intraoral radiographs were taken after insertion of the superstructure and at intervals of 1, 3, 5, 10, and 20 years. No implant or tooth loss occurred during the individual observation periods. Mucositis was recorded around 65% of the implants and was accompanied by additional maxillary marginal bone loss around 27.7% of the implants. Mean marginal bone loss at implant sites after 5 years was 0.75 ± 0.66 mm, and after 20 years was 1.50 ± 1.45 mm. Moderate bone loss around teeth was registered after 5 years (2.8%) and 20 years (7.3%). No significant differences were found between implants in patients with tooth-implant-supported and those with implant-supported double-crown restorations. These results suggest that severely periodontally compromised patients can be successfully managed in the long term with the described clinical protocol.

No evidence of excessive cancer screening in female noncarriers from BRCA1/2 mutation-positive families.

In families with a proven BRCA1/2 mutation, women not carrying the familial mutation should follow the cancer screening recommendations applying to women in the general population. In the present study, we evaluated the cancer screening practices of unaffected noncarriers from families with a proven BRCA mutation, and we assessed the role of family history in their screening practices. Self-report data were provided retrospectively by 220 unaffected female noncarriers for periods of up to 10 years (mean: 4.3 years) since disclosure of their BRCA1/2 genetic test result. A ratio for the annual frequency of breast and ovarian cancer screening exams (mammography, breast ultrasonography, breast magnetic resonance imaging, transvaginal or pelvic ultrasound, cancer antigen 125 testing) was calculated as number of screening exams divided by the number of years in the individual observation period. The annual average for mammography exams was 0.15, 0.4, 0.56, and 0.71 in women 30-39, 40-49, 50-59, and 60-69 years of age respectively. The uptake of other breast and ovarian cancer screening exams was very low. Mammography and breast ultrasonography and magnetic resonance imaging were generally more frequent among participants with at least 1 first-degree relative affected by breast cancer. In most noncarriers, screening practices are consistent with the guidelines concerning women in the general population. When noncarriers adopt screening behaviours that are different from those that would be expected for average-risk women, those behaviours are influenced by their familial cancer history. Decision tools might help female noncarriers to be involved in their follow-up in accordance with their genetic status and their family history, while taking into account the benefits and disadvantages of cancer screening.

Soil water regime and crop yields in relation to various technologies of cultivation in the Kulunda Steppe (Altai Krai)

This article presents the results of crop yield in areas with different technologies of cultivation based on the network of automatic stations that provide data on climatic and soil-hydrological monitoring in the dry steppe during the vegetation period of May–September 2013–2016 . These data on regional ecological and climatic parameters are of great interest to the ecologists, plant physiologists, and farmers working in the Kulunda Plain (Altai Territory). We compared the following options for cropping technologies: the modern system, which is the "no-till", technology without autumn tillage;the intensive technology of deep autumn tillage by plough PG-3-5 at a depth of 22–24 cm. Cultivation of crops was carried out using the following scheme of crop rotation: the modern system: 1–2–3–4 (wheat – peas – wheat – rape); the intensive system: 5/6 – 7/8 – 9/10 (fallow – wheat – wheat). We believe that the use of modern technology in these conditions is better due to exchange between the different layers of soil. When the ordinary Soviet system , the so-called "plow sole" , was used , at a depth of 24 cm , we observed that this creates a water conductivity barrier that seems to preclude the possibility of lifting water from the lower horizons. Results of the study of infiltration of soil moisture at the depth of 30 and 60 cm have shown in some years the advantages of the modern technology over the ordinary Soviet system: in the version with the use of modern technology we can trace better exchange between the various horizons and , probably, moisture replenishment from the lower horizons. Differences in individual observation periods are comparatively large due to the redistribution of soil moisture, depending on the weather conditions, the crops used in the crop rotations, and cultivation techniques. Moreover, the average moisture reserves within the one meter layer did not show any significant differences during the growing seasons of 2013–2016 . In terms of soil moisture usage and productive grain yield according to the four year experiment, the application of the modern technology with crop rotation "wheat – rape – wheat – peas" was more effective than the ordinary Soviet system with crop rotation "wheat – fallow – wheat – wheat". The four-year observation period is clearly insufficient to identify the advantages of the modern system, as during this time it is impossible to significantly improve soil quality indicators, which will continue to determine its water-retaining properties and moisture accumulation.

A Preliminary Study toward Consistent Soil Moisture from AMSR2

Abstract A preliminary study toward consistent soil moisture products from the Advanced Microwave Scanning Radiometer 2 (AMSR2) is presented. Its predecessor, the Advanced Microwave Scanning Radiometer for Earth Observing System (AMSR-E), has provided Earth scientists with a consistent and continuous global soil moisture dataset. A major challenge remains to achieve synergy between these soil moisture datasets, which is hampered by the lack of an overlapping observation period of the sensors. Here, observations of the multifrequency microwave radiometer on board the Tropical Rainfall Measuring Mission (TRMM) satellite were used to improve consistency between AMSR-E and AMSR2. Several scenarios to achieve synergy between the AMSR-E and AMSR2 soil moisture products were evaluated. The novel soil moisture retrievals from C-band observations, a frequency band that is lacking on board the TRMM satellite, are also presented. A global comparison of soil moisture retrievals against ERA-Interim soil moisture demonstrates the need for an intercalibration procedure. Several different scenarios based on filtering were tested, and the impact on the soil moisture retrievals was evaluated against two independent reference soil moisture datasets (reanalysis and in situ soil moisture) that cover both individual observation periods of the AMSR-E and AMSR2 sensors. Results show a high degree of consistency between both satellite products and two independent reference products for the soil moisture products retrieved from X-band observations. Care should be taken in the interpretation of the presented soil moisture products, and future research is needed to further align the AMSR2 and AMSR-E sensor calibrations.

Lymphedema of the upper limb: evaluation of the functional outcome by dynamic imaging of lymph kinetics after autologous lymph vessel transplantation.

The aim of this study was to evaluate by lymphoscintigraphy the functional outcome after autologous lymph vessel transplantation (Tx) of the upper limb. One hundred seventy-seven patients (172 female, 5 male; median age, 56 years; range, 12-84 years) presenting with Tx situs in an upper limb were included. For correlation of scintigraphic data versus reduction of volume (RV) surplus measurements, we examined at 4 different time points as follows: preoperatively (T0), within 2 weeks after Tx (T1), 6 to 12 months after Tx (T2), and 32 to 38 months after Tx (T3). An additional long-term follow-up after at least 8 years (T4) was available in some cases. The maximum individual postoperative observation period was 19 years. In 169 of 177 cases, lymphedema had been caused by treatment of breast cancer (mastectomy, n = 103/169; breast preserving, n = 66/169) and/or radiation therapy (n = 130/177), but 2 patients presented with primary lymphedema. The remaining 6 cases of lymphatic disorders were caused by treatment of malignant melanoma, Hodgkin lymphoma, axillary Ewing sarcoma, non-Hodgkin lymphoma, hemangioma, or abscess removal.At T1, the mean RV of the affected limb was 73%, and the mean improvement of transport index (TI) was 28%. At T2, the RV was 64% and the TI was 23%, and at T3, the RV was 63% and the TI was 25%. Long-term follow-up after at least 8 years (T4: range, 9-19.2; mean, 14.1 years) was available in 19 of 177 patients, in whom persistent improvement in the scintigraphic data (25% decrease in TI) was confirmed by a mean clinical RV of 68%. The mean overall correlation was by a factor of 2.64. Our findings in this large set of patients undergoing autologous lymph vessel Tx to an upper limb confirm that this microsurgical technique significantly and persistently improves lymph drainage in patients with lymphedema. The findings of lymphoscintigraphy correlated well with volume measurements at long-term follow-up.

FRI0233 Tocilizumab administered in daily clinical practice - final results of the german non-interventional study “routine”

BackgroundTocilizumab (TCZ) is an interleukin-6-receptor inhibitor for treatment of patients (pts) with rheumatoid arthritis (RA), which was approved in the EU in JAN 2009.ObjectivesTo evaluate the effectiveness, safety, and utilization...

Group Dynamics of Young Asian Elephant Bulls (Elephas maximus Linnaeus, 1758) in Heidelberg Zoo – Integration of a Newcomer in an Established Herd

The social organisation of elephants is based on female philopatry and male natal dispersal. The separation of males from their family group is a behavioural strategy of inbreeding avoidance. In the course of this gradual process young bulls increasingly have contact to males belonging to other herds, mainly same-aged, in form of sparring (Kurt & Garaϊ, 2006; Evans & Harris, 2008; Chiyo, Archie, Hollister-Smith, Lee, Poole, Moss, & Alberts, 2011) with spending more and more time away from their own family (Kurt, 2001; Kurt & Garaϊ, 2006; Poole & Moss, 2008). After leaving the natal herd they join other males and form loose all-male groups (McKay, 1973; Kurt, 2001; Poole & Moss, 2008). This natural process during the development of male elephants, however, raises a problem for the elephant keeping in zoological gardens because of the increasing intolerance by the herd in combination with the lack of adequate keeping facilities for bulls. As the keeping of young bulls without or limited contact to conspecifics is an unnatural way of handling them, as described above, efforts are made for establishing an appropriate husbandry. Zoo Heidelberg is the first German facility, which keeps a group of young elephant bulls. Moreover it is the first zoo which undertakes the experiment to integrate another young bull in an established group.The aim of this study was to assess the group dynamics, particularly the individual personalities and social bonds, in a group of young bulls in captivity during the integration of a new bull.By means of the focal animal sampling (Altman, 1974) the social behaviour of the four young bulls during the first four months of integration of the new bull was continuously recorded. It was quantified by the frequencies of defined social events and the individual duration of social isolation and association with another elephant. The durations and the frequencies were standardised as the percentage of the individual observation period and the number of occurrences per hour, respectively, in order to allow the comparison of the individuals.The four young bulls showed distinct personalities, which affected the strength and kind of social bonds between them. In general the members of the initial group interacted more frequently among themselves than they did with the new one. Particularly the initial three elephants exhibited physical contact and friendly behaviours to a greater extent than the new bull did. But the frequency and the motivation of the associations depended on the social partner both in the case of the initial group members and the new one. Furthermore the behaviour of the new elephant indicated social isolation and an elevated stress level. Beside a high frequency of social interactions, the existence of a dominance hierarchy and the progressive integration of the new bull suggest a stable social structure and therefore support the concept of keeping young bulls in same-sex groups.

Multicenter Randomized Clinical Trial: Early Loading of Implants in Maxillary Bone

The aim of this study was to show prognostic equivalence between implant loading in the maxilla after 12 weeks versus 4 weeks. One hundred four patients, from four centers in this open-labeled randomized multicenter prospective controlled clinical trial, were assigned to either 12 weeks or 4 weeks of unloaded healing. Two hundred sixty-nine implants (sand blasted large-grid, acid etched [SLA] surface, ≥ 4.1 mm diameter; ≥ 10 mm length) were inserted and evaluated during an individual 5-year follow-up. Primary outcome was implant success after 12 months; prognostic equivalence was characterized by a maximum difference of ± 5% in implant failure rates. Implant-wise 1-year failure rates were estimated 3.1% (5/163 implants) in the 4 weeks group versus 3.6% (4/112 implants) in the 12 weeks group (95% confidence interval [CI] for the difference -3.2 -+4.2%); implant-wise evaluation demonstrated statistically significant prognostic equivalence of 4 and 12 weeks loading. Patient-wise 1-year failure rates were estimated 6.7% (n = 4 patients) in the 4 weeks group versus 5.1% (n = 2 patients) in the 12 weeks group (95% CI for the difference -9.6 -+6.5%). All implant failures occurred within the first 3 months of the individual observation period. Prior bone augmentation, underdimensioned drilling, bone quality, implant type, implant length, implant diameter, residual teeth, and fixing of the restoration did not reveal associations with the implant outcome: trial site, posterior jaw region, and splinting were associated with a higher failure rate. Resonance frequency analysis did not serve as a predictor of implant failures at the time of implant insertion. Loading of standard SLA implants in the maxilla 4 weeks versus 12 weeks after insertion resulted in statistically equivalent failure patterns within a 1-year follow-up period; nevertheless, the observed patient-wise failure patterns of the interim analysis requires further understanding of patient-individual aspects of the early loading concept.

Transient violation of Le Chatelier’s principle for a network of water molecules

For a process in a small chemical system observed for short periods of time, the probability that it proceeds in the opposite direction to that found in the thermodynamic limit can be significant. We demonstrate this using simulations of a hydrogenbonded network of water molecules whose temperature is changed from 300 K to 310 K. It is shown that for this system, and finite periods (up to tenths of picoseconds), the change during an individual observation period might be in either direction which satisfies the transient fluctuation theorem for a temperature change (Journal of Chemical Physics, 131, 214503 (2009)).

Foraging behaviours of Diachasmimorpha kraussii (Fullaway) (Hymenoptera: Braconidae) and its host Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) in a nectarine (Prunus persica (L.) Batsch var. nectarina (Aiton) Maxim) orchard

Diachasmimorpha kraussii is a larval parasitoid of dacine fruit flies. Host utilisation behaviour, including field foraging behaviour, is poorly known in this species. The diurnal foraging behaviour of D. kraussii and one of its common hosts, Bactrocera tryoni, in a nectarine orchard was concurrently recorded. Observations of mating, resting, feeding and oviposition were taken two-hourly on 42 trees, commencing at 07:00 h and terminating at 17:30 h, for 17 days. Resting and oviposition were common events within the orchard for both species, while mating behaviours were not recorded in the orchard for either species. Feeding was not observed for D. kraussii and was rare for B. tryoni. At the level of the individual tree there was a very weak, but significant correlation between parasitoid and fly abundance over a day, but when broken down to the individual observation periods the correlations were absent, or were weakly significant in an inconsistent manner (i.e. sometimes positively correlated, sometimes negatively correlated). At the orchard level, abundance of the parasitoid was not correlated with adult fly abundance. Results suggest that D. kraussii forage independently to adult B. tryoni, a result consistent with a prediction that their foraging is largely driven by larval or plant damage cues.

Mortality and employment after in-patient opiate detoxification

AimWe considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification. MethodsThe cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years. ResultsThe standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p=0.003). ConclusionsThe assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.

Steroid‐induced Periorificial Dermatitis in Children—Clinical Features and Response to Azelaic Acid

Periorificial dermatitis, a common skin disease in young women, has been occasionally reported in children. This study elaborates the clinical features of periorificial dermatitis in children as well as possible pathogenetic factors and the response to 20% azelaic acid cream. A total of 10 children aged 3 to 12 (mean 7.7) years suffering from nongranulomatous periorificial dermatitis for 3 to 7 (mean 4.9) months were evaluated, and dermatologic examination was carried out. Pretreatment was documented. Skin prick tests with a panel of six common inhalative allergens and patch tests with the European Standard Series were performed. An association between atopy and periorificial dermatitis was evaluated, and patients were screened for skin colonization by fungi, bacteria, and Demodex mites. They were treated with 20% azelaic acid cream, which was topically applied twice daily on all affected areas, until complete resolution was achieved. Treatment period was followed by an individual observation period. Periorificial dermatitis had developed in typical distribution and morphology. In all patients, low- to high-potency topical corticosteroids had been used on the face prior to manifestation. Atopy was found in half of the patients. Allergological, bacteriological, and mycological examinations did not reveal pathologic results. Demodex mites could not be demonstrated by skin surface biopsy. Treatment with 20% azelaic acid cream led to complete resolution of skin lesions after 4 to 8 (mean 5.4) weeks in all patients. Transient exacerbation of skin condition with a peak between the 2nd and 6th day of treatment could be observed in three patients. Side effects of 20% azelaic acid cream were registered in six patients and were predominantly present in the first 2 weeks of treatment. Side effects were minimal and became rarer with ongoing treatment. No recurrences were seen within a follow-up period of 2 to 8 (mean 4.4) months. Treatment with 20% azelaic acid cream could provide an effective and safe alternative therapeutic option in children with nongranulomatous periorificial dermatitis.

Retrospective observational assessment of statin adherence among subjects patronizing different types of community pharmacies in Canada.

Community pharmacies vary widely in terms of ownership structures, location, and dispensing policies. It is unknown if an association exists between the type of community pharmacy and the degree of medication adherence exhibited by patrons-patients.To describe adherence to statin therapy among subjects patronizing different types of community pharmacy categories (department- mass merchandise, chain-franchise, and independent-banner) in Saskatchewan, Canada, between 2000 and 2005.Study data were obtained from the Saskatchewan Drug Plan and Extended Benefits database, which is maintained by the government of Saskatchewan, Canada. The study included all subjects who (a) filled a statin prescription within selected community pharmacies between January 1, 2000, and December 31, 2005; (b) had no record of statin prescriptions during the year prior to the first statin prescription, according to the records of the Saskatchewan Drug Plan and Extended Benefits; and (c) demonstrated active utilization in the drug plan database for at least 1 year after the first statin prescription. The proxy criterion for activity was any dispensing record for statin or nonstatin medications at least 1 year following the index claim. Statin adherence level was estimated as tablets per day, defined as the total number of tablets dispensed divided by the total number of days of observation. Each subject's observation period began on the index date and ended on the earlier of (a) 30 days after the last recorded fill for any type of prescription medication (statin or nonstatin), or (b) December 31, 2005. The primary end point was the proportion of subjects within each pharmacy category who maintained an adherence level of 80% or greater during their individual observation period. Additional adherence calculations were performed for each of 3 time periods, beginning on the index date and ending on days 365, 729, and 1094 (i.e., 1, 2, and 3 years). Patients were included in the analysis for each time period if they met a proxy criterion for availability for observation, defined as the dispensing of any drug at least 1 day after the end date of each period. Pearson chi square tests were used to assess the significance of differences in baseline characteristics and adherence proportions, comparing pharmacy categories. Logistic regression analysis estimated the odds of an adherence level of at least 80% during the individual observation period, adjusting for pharmacy category, sex, age 65 years or older, known low-income drug coverage, number of distinct drug classes filled concurrently during the first year of observation, loyalty to index pharmacy, and length of observation. Using similar methods, we also estimated "pharmacy loyalty" by calculating the proportion of subjects who refilled 75% or more of their statin prescriptions at the pharmacy that dispensed their first statin prescription.From an initial sample of 12,818 subjects who had at least 1 pharmacy claim for a statin in the period from January 1, 2000, through December 31, 2005, 8699 subjects met the inclusion criteria. Subjects were observed for a mean (SD, range) of 3.7 (1.7, 1.0-7.0) years after the index statin prescription. During the first year following the index claim, statin adherence rates were at least 80% for 1799 of 3761 (47.8%) patrons of department-mass merchandise, 1778 of 3235 (55.0%) patrons of chain-franchise, and 921 of 1703 (54.1%) patrons of independent-banner stores (P < 0.001). Measured from the index date through day 1094, 869 of 2292 (37.9%), 874 of 1887 (46.3%), and 457 of 975 (46.9%) subjects in the department-mass merchandise, chain-franchise, and independent banner categories, respectively, had a statin adherence level of at least 80% (P < 0.001). In logistic regression analysis, pharmacy category type was significantly associated with statin adherence; subjects in the chain franchise and independent-banner categories were more likely to be adherent to their statin medications during their observation periods than were those in the department-mass merchandise category (adjusted odds ratio [OR] = 1.36, 95% CI = 1.23-1.50, P < 0.001 and OR = 1.39, 95% CI = 1.24-1.57, P < 0.001, respectively). From the index date through day 1094, 1752 of 2292 (76.4%), 1475 of 1887 (78.2%), and 795 of 975 (81.5%) subjects remained pharmacy-loyal in the department-mass merchandise, chain franchise, and independent-banner categories, respectively (P = 0.006). Controlling for several potential confounders using logistic regression, independent-banner pharmacy patrons were more likely to remain pharmacy- loyal during their observation periods than were those patronizing department-mass merchandise (adjusted OR = 1.34, 95% CI = 1.16-1.54, P < 0.001) or chain-franchise stores (adjusted OR = 1.22, 95% CI = 1.06-1.42, P = 0.009).One year after their first statin fill, subjects demonstrated low rates of adherence, ranging from 48% to 55%, regardless of the type of pharmacy they patronized. Although the differences by type of pharmacy reached statistical significance, their clinical importance is not evident, reinforcing the fact that the problem of nonadherence appears to exist among all types of community pharmacies, regardless of their categorization.

Pinimenthol® ointment in patients suffering from upper respiratory tract infections – A post-marketing observational study

In order to gain further experience regarding the tolerability of Pinimenthol ointment(1) in adolescents (> or = 12 years) and adults suffering from upper respiratory tract infections, a post-marketing observational study was performed. In this study, data of 3060 patients were collected (64.9% prospectively over an individual observation period of 5-14 days, 35.1% retrospectively). The prospective documentation also comprised data concerning treatment effects. Sample size of the post-marketing observational study was calculated in the way that adverse drug reactions with an event probability of at least 1:1000 would occur within the study at least once with a probability of 95%. Most patients suffered from cold, acute or chronic bronchitis, bronchial catarrh or hoarseness. Pinimenthol ointment was prescribed to inunction (29.6%), inhalation (17.3%) or inunction and inhalation (53.1%), respectively. The mean duration of study participation was 8.0 +/- 3.4 days. The tolerability was rated as excellent or good by 96.7% of physicians and 95.7% of patients. A total of 22 patients (0.7%) reported adverse drug reactions which mostly affected the skin or mucus membrane and therefore correspond to the expected adverse effects profile of Pinimenthol ointment. The treatment effect was mostly judged as excellent or good (physicians: 88.3%; patients: 88.1%). In conclusion, the study confirms Pinimenthol ointment as a well tolerated therapy option for upper respiratory tract infections in both adolescents and adults.

HAART is neuroprophylactic in HIV-1 infection.

To find out about the prophylactic value of antiretroviral therapy on HIV-1-associated subclinical and clinical psychomotor slowing as one marker of HIV-1-associated CNS disease. Prospective study with regular clinical and neurophysiologic examination every three months of 1482 consecutive HIV-1-seropositive and AIDS patients seen at our department till June 30, 1999. Antiretroviral therapy has a significant prophylactic value over an individual observation period of ten years with regard to the first, potentially transient manifestation of HIV-1-associated subclinical psychomotor slowing and with regard to the clinical manifestation of motor signs. However, a subgroup of patients is characterized through a second, more sustained manifestation of subclinical psychomotor slowing which cannot be prevented by any type of currently available antiretroviral therapy. These findings suggest the existence of different pathomechanisms underlying HIV-1-associated brain disease which may in part be effectively prevented, but which in part also escape all antiretroviral treatment strategies in use today.

Fluctuations in HIV-1 Viral Load Are Correlated to CD4+ T-Lymphocyte Count During the Natural Course of Infection

Viral load fluctuates during the natural course of asymptomatic HIV-1 infection. It is often assumed that these fluctuations are random around a set point or underlying growth trend. Using longitudinal data, we tested whether fluctuations in viral load can be better explained by changes in CD4+ T-cell count than by a set point or trend of exponential growth. The correspondence between viral load and CD4+ T-cell count could be described by a simple mathematical relation. Using a bootstrapping approach, the hypothesis that viral load fluctuations are random around a set point was rejected with p < .00005. The hypothesis that viral load fluctuations are random around a trend of exponential growth was rejected with p < .005. Viral load data was explained better by changes in CD4+ T-cell counts than by a set point or by a trend of exponential growth. The implications of this finding for improved prognostication are discussed.

Human Clinical and Histologic Responses to the Placement of HTR Polymer Particles in 11 Intrabony Lesions

Eleven intrabony periodontal lesions in five volunteer patients received surgical debridement followed by site implantation of a porous particulate polymeric composite (HTR polymer). These patients were observed over time periods varying from 4 weeks to 26 weeks. At the end of the individual observation periods, treated sites were surgically removed in block for histologic analysis. Clinical observations indicated a reduction in pocket depth following treatment which consisted of both gingival recession and gain in clinical closure. No untoward effects were observed clinically in any treated patient during the observation periods. Histologic responses varied from gain in closure by epithelial adhesion to new attachment of varying magnitude. Such varied responses were seen within the same patient and between patients. Graft particles were present at sites from 4 weeks to 26 weeks after implantation and were surrounded by connective tissue capsules. At the periphery of some particles, limited bone formation was present. The alveolar bed was remodeling, at times surrounding specific particles. In our sample, HTR polymer, therefore, appeared to be a well tolerated synthetic graft material when implanted in human intrabony lesions.