Changing a profession, influencing community pharmacy

The authors set out to describe the possible impact of the continuing education activities of the Community Pharmacy Section (CPS) of the International Pharmaceutical Federation (FIP) on the profession in the period from 1980 to 2002 (approximately the last two decades of the 20th century) by reviewing and interpreting documents of the Community Pharmacy Section of the International Pharmaceutical Federation. The educational activities of the CPS have resulted in a high level of satisfaction among the participants. The CPS has also coordinated international practice research and the dissemination of the concept of pharmaceutical care. Additionally, the section's activities have informed the members of national pharmaceutical associations about new concepts, and stimulated projects on the added value of pharmacy. There are reasons to believe that the activities have created agents of change. It seems that the activities of the section have had some effect, although the exact impact remains difficult to measure because no structured evaluation method has been applied from the beginning of the continuing education activities.     

Assessment of reproducibility of measures of intraocular pressure and central corneal thickness in young white adults over a 16-h time period

PURPOSE: The aims of this study were to obtain clinical measures of intraocular pressure (IOP) and central corneal thickness (CCT) and during waking hours to further assess both the nature of diurnal changes, and the reproducibility of any possible association between the two measures. METHODS: Fifteen white (Norwegian) healthy young adult subjects aged 20-29 years had IOP and CCT measures made, using a non-contact specular microscope and non-contact tonometry (NCT), every hour over a period of 16 h, starting at 06.30 hours. The experiment was repeated on two successive days. RESULTS: The average NCT readings were 12.5 and 11.4 mmHg for days 1 and 2, while pachometry averages were 0.518 and 0.514 mm. The range of NCT values, for any set of readings, averaged 2 mmHg, while this range was 0.014 mm for CCT measures. The reproducibility of these measures, as estimated by the coefficient of variation (COV) was 7.2% for NCT and 1.0% for pachometry measures. The COV for tonometry was inversely proportional to the actual values of these measures. A significant time-related decline in tonometry values was seen over day 1 but not day 2. Pachometry values declined very rapidly over the first hour in both sessions and were essentially constant for the rest of the sessions. The strongest association between pachometry data and NCT measures was noted around midday (12.30 hours) on both sessions. CONCLUSIONS: These studies confirm that the reproducibility (repeatability) of NCT and pachometry are substantially different. It is suggested that this aspect of tonometry needs to be taken into account, especially where there are lower values, when considering the possible impact of corneal thickness on tonometry measures and their interpretation. These types of effects need to be further assessed in older patients with ocular hypertension, or other glaucoma suspects.     

The problem of the children; waifs of the city's slums

Jacob Riis was born in 1849 in Denmark and arrived at the Port of New York in 1870. After seven years of semi-poverty he became a police reporter covering the tenements on the city's east side. During the post-Civil War period industrialization, urbanization, and immigration had combined to undermine living conditions in the quickly growing cities of America. It was about life in the tenements of these cities that Riis wrofe.HisHow the Other Half Lives had a major impact on the nation, drawing attention to the terrible conditions of the lives that were led in the tenements. The excerpt reprinted here, like the rest of the book, forced the nation to see what it was doing to its children.Riis's work can be seen as part of the great turn-of-the-century effort from which the social sciences and social welfare services emerged, or it can still function as a prod to action, raising indignation on behalf of the children of the 1990s, as it did for those of the 1890s.Reprinted with permission fromHow the Other Half Lives: Studies among the Tenements of New York, by Jacob A. Riis. New York: Hill and Wang, 1957.     

Plasma levels of parathyroid hormone,vitamin D,calcitonin, and calcium in association with endurance exercise

Summary Nine male marathon runners were investigated during habitual training (week 0), after 3 weeks of training break (week 3), and after 2 weeks (week 5) and 4 weeks (week 7) of retraining. Maximal oxygen uptake, body fat (BF), and plasma levels of 25(OH)D₃, 1,25(OH)₂D₃, parathyroid hormone (PTH), calcitonin (CT), albumin, and albumincorrected calcium were determined throughout weeks 0–7. The maximal oxygen uptake decreased after training break and increased during retraining (P=0.002). BF did not change significantly. Plasma 1,25(OH)₂D₃ was elevated after training break and decreased after 2 and 4 weeks of retraining [week 0: 44.0±3.7 (SEM) pg×1^-1; week 3: 52.4±6.0 pg×1^-1; week 5: 42.0±2.8 pg×1^-1; week 7: 36.9±2.3 pg×1^-1; P=0.03]. Plasma 25(OH)D₃ did not change significantly. Plasma PTH increased throughout the training break and retraining (week 0: 1.36±0.25 pmol×1^-1; week 3: 2.02±0.43 pmol×1^-1; week 5: 2.23±0.60 pmol×1^-1; week 7: 2.63±0.34 pmol×1^-1; P=0.03). Albumincorrected calcium values were transiently decreased during retraining (week 3: 2.77±0.08 mM; week 5: 2.47±0.05 mM; week 7: 2.66±0.07 mM; P=0.01). Plasma CT did not change during training break, but was transiently decreased during retraining (week 0: 9.97±0.39 pmol×1^-1; week 3: 9.91±0.37 pmol×1^-1; week 5: 8.19±0.50 pmol×1^-1; week 7: 9.02±0.45 pmol×1^-1; P=0.01). Plasma CT was correlated to albumin (r=0.46, P=0.005), albumin-corrected calcium (r=0.34, P=0.04), and maximal oxygen uptake (r=0.45, P=0.006). Plasma 1,25(OH)₂D₃ was correlated to 25(OH)D₃ (r=0.04, P=0.02), and BF (r=0.50, P=0.002). The described endurance training induced significant changes of plasma 1,25(OH)₂D₃ and PTH despite only transient changes of albumin-corrected calcium and CT.     

Gender and age related differences in left ventricular function and geometry with focus on the long axis.

AIMS: To study age and gender related alterations in left ventricular (LV) long axis function. METHODS: Eighty-two healthy individuals from the general population in three age groups were investigated. LV long axis and short axis function and dimensions were studied with echocardiographic M-mode and two-dimensional technique. RESULTS: The most prominent age related differences were observed in LV long axis function, whereas only minor alterations in short axis function were noticed. Both systolic and diastolic long axis function decreased with advancing age; maximal systolic velocity (r=0.61, p<0.0001), maximal early diastolic filling velocity (r=0.87, p<0.0001). The length of the long axis decreased with age, while the relative contraction amplitude was maintained. LV global and short axis measurements revealed significant differences between genders, males having generally larger dimensions, even when correcting for body surface area. Females exhibited a more pronounced remodelling process with advancing age. CONCLUSION: Functional age related changes in LV function are more prominent in the long axis, while differences between genders are more pronounced in short axis and in volume measurements. These findings might be of importance when remodelling processes are evaluated, as these appear to be different in men and women and also age related.     

Dose-toxicity relationship of carboplatin in combination with cyclophosphamide in ovarian cancer patients

Summary A study was undertaken to examine the relationships between carboplatin's pharmacokinetic parameters and the myelotoxicity associated with its administration in combination with cyclophosphamide. An additional aim of the study was to test the applicability of the method proposed by Calvert et al. for calculation of the carboplatin dose to be used in the combination regimen. A total of 24 previously untreated ovarian cancer patients were given a combination of 250–500 mg/m² carboplatin and 500 mg/m² cyclophosphamide every 4 weeks for 4 months. The pharmacokinetics of carboplatin and the associated myelotoxicity were investigated in 64 courses. The results showed a significant correlation (r=0.89) between the AUC calculated for carboplatin and that predicted according to Calvert's formula [carboplatin dose in milligrams=AUC (glomerular filtration rate +25)]. We conclude that the model is a useful guide in the calculation of the carboplatin dose to be given in combination with cyclophosphamide, and it enables a more precise prediction of the carboplatin exposure than does the conventional calculation, which is based on milligrams of drug per square meter of body surface. The AUC for carboplatin was a reliable predictor of the myelotoxicity as measured by the relative decrease in thrombocyte count. However, the relationship between AUC and myelotoxicity changed during the treatment because of increasing bone marrow toxicity. Despite this finding, dose calculation based on carboplatin's AUC appears to provide an improvement in the clinical use of the drug, and the method also seems to be fully applicable in combination chemotherapy with cyclophosphamide.Supported by grants from the Lundbeck Foundation and the Danish Cancer Society     

Elimination of alkaline phosphatases from circulation by the galactose receptor. Different isoforms are cleared at various rates

Three isoforms of human alkaline phosphatase (liver, bone and placental ALP) were purified and their elimination studied after intravenous injection in rats. The rates of elimination were significantly inhibited by prior injection of asialofetuin, indicating that the uptake was mediated by the galactose receptor in liver. Their relative clearance rates differed, being rapid for the bone ALP, significantly slower for the liver isoform and very slow for the placental ALP. The bone ALP showed a rapid initial clearance, apparently related to its large glycan heterogeneity and to the presence of molecules with a low sialic acid content. When isolated from serum the liver and bone ALP isoforms showed clearance rates differing slightly from those of the organ derived forms. We conclude that differences in carbohydrate structure and amount of sialic acid of the three isoforms result in various clearance rates. These differences will also affect their serum concentrations as well as the composition and heterogeneity of the individual isoforms in serum.     

Aneuploidy and elevated CEA indicate an increased risk for metachronous metastasis in colorectal cancer

Purpose

Presently, no markers exist to predict metachronous metastasis at the time a primary colorectal cancer is diagnosed. While aneuploidy indicates poor survival prognosis and elevated carcinoembryonic antigen (CEA) levels the presence of recurrent disease, the predictive value of both markers regarding imminent metachronous metastases is unclear.

Methods

Sixty patients with distant recurrence throughout a 5-year follow-up (TM+) were randomly chosen and 60 patients without metastasis matched to this cohort (TM?). In addition, an enlarged collective (n?=?217; n _TM+?=?85, n _TM-?=?132) with median follow-up of 79.2 months was assessed by logistic regression regarding metachronous metastases. Univariate and stepwise regression analyses included clinicopathological characteristics, preoperative CEA levels and aneuploidy assessed by DNA image cytometry.

Results

The matched-pair collective showed aneuploidy in 71.1 % (TM?) and 85.0 % (TM+; p?=?0.076), and elevated CEA in 24.5 % (TM?) and 52.2 % [TM+; odds ratio (OR), 3.414; p?=?0.007]. The enlarged collective presented aneuploidy in 71.2 % (TM?) and 83.5 % (TM+; OR 2.050, p?=?0.038), and elevated CEA in 28.6 % (TM?) and 48.9 % (TM+; OR 2.391, p?=?0.020). Elevated CEA and aneuploidy did not show any association (p?=?0.919). In contrast, logistic regression analyses demonstrated that besides increased T category (OR 1.745, p?=?0.019), both elevated CEA level (OR 2.633, p?=?0.015) and aneuploidy (OR 1.929, p?=?0.058) were independent predictive markers for metachronous metastasis.

Conclusions

Our data show that aneuploidy and elevated CEA levels besides increased T category could serve for individual risk assessment to predict metachronous metastases. The fact that still aneuploidy missed the significance level by a small margin emphasizes the need for larger validation studies.     

A Newly Identified Deletion of 970 bp at the α-Globin Locus That Removes the Promoter Region of the α1 Gene

The most common causes of α-thalassemia (thal) are deletions that remove a part, or one or both of the functional α-globin genes. These deletions cause diminished expression of the α-globin protein, which may result in relatively low hemoglobin (Hb) and/or mean corpuscular volume (MCV) values. We here report the identification of a 970 bp deletion in the α1-globin gene that encompasses the entire promoter region of the α1-globin gene and 26 bp encoding the 5′ end of the mRNA. Thus, the affected α1-globin gene is prone to be nonfunctional. We therefore nominated the newly identified deletion allele α?α^Δ970. The MCV values of four related carriers of the α?α^Δ970 allele were slightly lowered, consistent with the presence of three functional α-globin genes.     

Clinical Response,Drug Survival,and Predictors Thereof Among 548 Patients With Psoriatic Arthritis Who Switched Tumor Necrosis Factor α Inhibitor Therapy: Results from the Danish Nationwide DANBIO Registry

Objective

To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care.

Methods

We conducted an observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated using the American College of Rheumatology criteria for 20% improvement (ACR20)/ACR50/ACR70, European League Against Rheumatism (EULAR) response criteria for good response, and the 28‐joint count Disease Activity Score (DAS28) (remission). Kaplan‐Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after treatment switching.

Results

Of 1,422 patients starting TNFi agents, 548 patients (39%) switched to a second biologic drug during up to 10 years of followup. Median followup was 2.3 years (interquartile range [IQR] 1.0–4.3 years). Switchers were more frequently women (56% versus 45%), had a shorter disease duration (3 versus 4 years), a higher median Health Assessment Questionnaire (HAQ) score (1.1 [IQR 0.6–1.6] versus 0.9 [IQR 0.5–1.4]), DAS28 (4.8 [4.0–5.7] versus 4.4 [3.6–5.2]), pain score on a visual analog scale (VAS) (65 mm [46–77] versus 62 mm [40–75]), and fatigue score on a VAS (69 mm [50–83] versus 64 mm [42–80] mm) (all P < 0.05 at start of first TNFi). During the first and second treatment, HAQ, DAS28, and VAS scores and C‐reactive protein levels had decreased after 6 months (all P < 0.05), and median drug survival was 2.2 versus 1.3 years (P < 0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving a sustained ACR20, ACR50, ACR70, EULAR good response, and DAS28 remission after 3–6 months were 22% (number needed to treat [NNT] 4.5), 13% (NNT 7.9), 5% (NNT 20), 19% (NNT 5.3), and 34% (NNT 2.9), respectively. Response rates were lower during the second treatment (all P < 0.01 versus first TNFi). At the 2‐year visit, 47% of switchers had achieved an ACR20 response. No differences between drug–drug combinations were found.

Conclusion

Thirty‐nine percent of the patients with PsA switched TNFi agents. Response rates and drug survival were lower after switching; however, half of the switchers had an ACR20 response 2 years after starting the first TNFi.