Do unions contribute to creative destruction?

We apply a shift-share approach and historical unionisation data from 1918 to study the impact of regional unionisation changes in Norway on regional wage and productivity growth, job-creation and -destruction and social security uptake during the period 2003-2012. As unionisation increases, wages grow. Lay-offs through plant closures and shrinking workplaces increase, causing higher retirement rates, while job creation, plant entry and other social security uptakes are unaffected. Productivity grows, partly by enhanced productivity among surviving and new firms and partly by less productive firms forced to close due to increased labour costs. Thus, unions promote creative destruction.

Gender difference in sickness absence: Do managers evaluate men and women differently with regard to the appropriateness of sickness absence?

Aims: Women have much higher rates of sickness absence than men, but the causes of the difference are not well understood. This study examines whether managers have more lenient attitudes towards women's than towards men's absence, as this might contribute to higher rates of sickness absence among women. Differences between managers and other employees are also assessed. Methods: Vignettes were used to measure attitudes towards the legitimacy of sickness absence. The vignettes consisted of brief case descriptions of individuals considering asking their physicians for sick leave, with information about the medical condition (mainly taken from the descriptions in ICPC-2), occupation and gender. Respondents judged how appropriate sickness absence was in each case. Quota sampling was used, and the effective sample size was 899 managers and 1396 other employees, with each respondent evaluating either four or six vignettes. Generalised ordinal logistic regression was used. Results: The gender of the vignette person had no effect on the managers' evaluations of the appropriateness of sickness absence. Irrespective of the gender of the vignette person, however, managers were generally more restrictive than non-managers. Conclusions: Different attitudes on the part of managers towards sickness absence in men and women do not seem to contribute to gender differences in sickness absence, but managers are generally more restrictive compared to non-managerial employees.

Gender equality in sickness absence tolerance: Attitudes and norms of sickness absence are not different for men and women.

Previous research offers limited understanding as to why sickness absence is higher among women than among men, but attitudes and norms have been suggested as plausible explanations of this gender gap. The purpose of the present study is to examine whether the gender gap in sickness absence reflects gender differences in sickness absence attitudes or gendered norms of sickness absence in society. The analyses are based on data from a factorial survey experiment covering 1,800 male and female employed respondents in Norway in 2016. Each participant was asked to evaluate whether sick leave would be reasonable in six unique, hypothetical sickness absence scenarios (i.e. vignettes) in which occupation, gender and reason for sick leave varied. Sick leave judgments were regressed on respondent gender and vignette gender using binary logistic regressions across three cut points. Overall, we did not find a substantial gender difference in either attitudes towards sickness absence or sickness absence norms. However, further analyses indicated more tolerant social norms of sickness absence for employees in gender-dominated occupations than for employees in gender-integrated occupations. This pattern could be a result of the type of work attributed to these occupations rather than their gender composition. Contrary to popular belief, we conclude that widely held attitudes and norms of sickness absence are unlikely to be drivers of the gender gap in sickness absence. The results can be useful for policies and interventions aimed at safeguarding gender equality in the labour market.

Validation and use of microdialysis for determination of pharmacokinetic properties of the chemotherapeutic agent mitomycin C - an experimental study.

BACKGROUND: Mitomycin C is a chemotherapeutic agent used in the treatment of peritoneal surface malignancies, administered as hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Pharmacokinetic studies have been based on analyses of blood, urine and abdominal perfusate, but actual tissue concentrations of the drug have never been determined. Microdialysis is an established method for continuous monitoring of low-molecular substances in tissues, and in the present study microdialysis of mitomycin C was studied in vitro and in vivo. METHODS: Using in vitro microdialysis, relative recovery was determined when varying drug concentration, temperature and perfusion flow rate. In vivo microdialysis was performed in rats to verify long-term stability of relative recovery in four compartments (vein, peritoneum, extraperitoneal space and hind leg muscle). Subsequently, intravenous and intraperitoneal bolus infusion experiments were performed and pharmacokinetic parameters were calculated. RESULTS: In vitro, compatibility of mitomycin C and microdialysis equipment was demonstrated, and relative recovery was stable over an adequate concentration range, moderately increased by raising medium temperature and increased when flow rate was reduced, all according to theory. In vivo, stable relative recovery was observed over seven hours. Mitomycin C exhibited fast and even distribution in rat tissues, and equal bioavailability was achieved by intravenous and intraperitoneal infusion. The half-life of mitomycin C calculated after intravenous infusion was 40 minutes. CONCLUSIONS: Mitomycin C concentration can be reliable monitored in vivo using microdialysis, suggesting that this technique can be used in pharmacokinetic studies of this drug during hyperthermic intraperitoneal chemotherapy.

Pharmacokinetic analysis of two different docetaxel dose levels in patients with non-small cell lung cancer treated with docetaxel as monotherapy or with concurrent radiotherapy.

BACKGROUND: Previous pharmacokinetic studies with docetaxel have mostly used 3-weekly (75 mg/m2 and 100 mg/m2) or weekly regimens (35-40 mg/m2). The pharmacokinetics and radiosensitizing efficacy of weekly 20 mg/m2 docetaxel, has however not been well characterized. We examined the pharmacokinetics of weekly docetaxel when administered with concurrent radiotherapy and compared the results with a 3-weekly 100 mg/m2 regimen. METHODS: Thirty-four patients with non small cell lung cancer (NSCLC) were included in this study, 19 receiving 100 mg/m2 docetaxel 3-weekly as single therapy, and 15 receiving 20 mg/m2 docetaxel weekly with concurrent radiotherapy. A newly developed HPLC method was used for measuring docetaxel levels, capable of quantifying docetaxel in plasma down to the nanomolar level. RESULTS: The HPLC method showed detectable concentrations of docetaxel in plasma even after 72 hours. In the present study we have demonstrated that median docetaxel plasma levels of 3 nM can be obtained 72 hours after a dose of 20 mg/m2. CONCLUSION: The pharmacokinetics of docetaxel is characterized by great inter-individual variability and at some time points plasma concentrations for 20 mg/m2 and 100 mg/m2 docetaxel were overlapping. Extrapolation of these results indicates that radio sensitizing docetaxel concentrations may be present for as long as 1 week, thus supporting the use of 20 mg/m2 weekly docetaxel.

Tobramycin once versus three times daily, given with penicillin G, to febrile neutropenic cancer patients in Norway: a prospective, randomized, multicentre trial.

OBJECTIVES: Penicillin G with an aminoglycoside is the standard initial empirical treatment in febrile neutropenia in Norway. It has been argued that giving the aminoglycoside once daily to neutropenic patients with Gram-negative bacteraemia may be hazardous when penicillin G is the beta-lactam antibiotic. We questioned this argument and hypothesized that tobramycin once daily was as efficacious as three times daily. METHODS: We conducted a randomized prospective multicentre study, comparing the efficacy of tobramycin 6 mg/kg once (arm A) versus three times (arm B) daily, plus penicillin G 5 million IU x 4, in febrile neutropenic cancer patients. PRIMARY OUTCOME: modification of the antibiotic regimen. RESULTS: One hundred and seventy-four patients were evaluable for intention-to-treat analyses. One hundred and fifty-five patients had lymphoma or leukaemia as the underlying cancer diagnosis. In arm A, 35 of 88 patients and in arm B, 34 of 86 patients, that is 40% in both arms had no modification of the antibiotic regimen. No patients died while participating in the study. Upon modification of the antibiotic regimen, all patients were successfully treated. The increase in serum creatinine was modest and similar in the two treatment groups. CONCLUSIONS: When administered with penicillin G, tobramycin given once daily was as efficacious and safe as tobramycin given three times daily in cancer patients with febrile neutropenia in Norway, provided the regimen was modified according to the clinical response.

High sensitivity assays for docetaxel and paclitaxel in plasma using solid-phase extraction and high-performance liquid chromatography with UV detection.

BACKGROUND: The taxanes paclitaxel and docetaxel have traditionally been used in high doses every third week in the treatment of cancer. Lately there has been a trend towards giving weekly low doses to improve the therapeutic index. This article describes the development of high performance liquid chromatographic (HPLC) methods suitable for monitoring taxane levels in patients, focusing on patients receiving low-dose therapy. METHODS: Paclitaxel and docetaxel were extracted from human plasma by solid phase extraction, and detected by absorbance at 227 nm after separation by reversed phase high performance liquid chromatography. The methods were validated and their performance were tested using samples from patients receiving paclitaxel or docetaxel. RESULTS: The limits of quantitation were 1 nM for docetaxel and 1.2 nM for paclitaxel. For both compounds linearity was confirmed from the limit of quantitation up to 1000 nM in plasma. The recoveries ranged between 92% and 118% for docetaxel and between 76% and 104% for paclitaxel. Accuracy and precision were within international acceptance criteria, that is within +/- 15%, except at the limit of quantitation where values within +/- 20% are acceptable. Low-dose patients included in an on going clinical trial had a median docetaxel concentration of 2.8 nM at 72 hours post infusion. Patients receiving 100 mg/m2 of paclitaxel had a mean paclitaxel concentration of 21 nM 48 hours after the end of infusion. CONCLUSION: We have developed an HPLC method using UV detection capable of quantifying 1 nM of docetaxel in plasma samples. The method should be useful for pharmacokinetic determinations at all relevant doses of docetaxel. Using a similar methodology paclitaxel can be quantified down to a concentration of 1.2 nM in plasma with acceptable accuracy and precision. We further demonstrate that the previously reported negative influence of Cremophor EL on assay performance may be overcome by degradation of the detergent by incubation with lipase.

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo.

RATIONALE: The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered. OBJECTIVE: This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo. METHODS: Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers ( n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo. RESULTS: Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response. CONCLUSIONS: Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.

Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro.

BACKGROUND: Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company. METHODS: The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism. RESULTS: The drugs were highly bound to albumin (95-99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilizers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilizers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity. CONCLUSION: This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen no longer detectable in pharmaceutical-grade albumin. It further shows that the addition of stabilizers may be of major importance for this effect.

[Use of naltrexone in the treatment of young drug addicts]. / Behandling av unge stoffmisbrukere med naltrekson.

BACKGROUND: The study explores the use of naltrexone as an adjuvant therapy for psychosocial treatment in a unit for young heroin addicts with frequent relapses. MATERIAL AND METHOD: Naltrexone was introduced through discussions in the therapeutic community. 16 patients elected to participate in a six-month trial. Side effects were recorded daily, then weekly, and patient reactions by weekly self-ratings. At end point patient and counsellor independently scored estimated utility. The group was followed up at four years. RESULTS AND INTERPRETATION: Staff and patients developed an increasing degree of consensus during the project. Naltrexone is a useful adjuvant therapy. Several short-term goals were reached; side effects were minimal. Four out of 16 patients completed the full six-month treatment. 11 patients judged the use of naltrexone as somewhat or very positive. Therapists judged naltrexone to be beneficiary for 10. At four years follow up, six patients were rehabilitated without illegal substance use and two were substantially improved. Four of these were, however, on methadone maintenance. Naltrexone is useful as an adjuvant therapy to increase therapeutic potency in comprehensive therapeutic units for heroin addicts. The long-term effects are limited. Therapeutic units for heroin addicts should integrate both agonists and antagonists in their psychosocial programs.