Consultation prevalence among children, adolescents and young adults with pain conditions: A description of age- and gender differences.

BACKGROUND: Pain is a common complaint presented in healthcare, but most epidemiological pain research has focused either on single pain conditions or on the adult population. The aim of this study was to investigate the 2017 consultation prevalence of a wide range of pain conditions in the general population of young people. METHODS: We used the Skåne Healthcare Register, covering prospectively collected data on all healthcare delivered (primary and secondary care) to the population in the region of Skåne, southern Sweden (population 2017 n = 1,344,689). For individuals aged 1-24 in 2017 (n = 373,178), we calculated the consultation prevalence, stratified by sex and age, and the standardised morbidity ratio (SMR) to assess overall healthcare consultation. RESULTS: A total of 58,981 (15.8%) individuals consulted at least once for any of the predefined pain conditions. Of these, 13.5% (n = 7,996) consulted four or more times for pain. Abdominal pain, joint pain/myalgia, headache and back/neck pain were the most common complaints. Overall, females had higher consultation prevalence than males: 17.6% versus 14.1% (p < .0001). SMR was 1.82 (95% CI = 1.74-1.87) for females with pain and 1.51 (95% CI = 1.42-1.56) for males with pain. Consultation prevalence increased with age, but this pattern varied between sex and pain condition. CONCLUSIONS: Among individuals under the age of 25, a significant proportion consult for pain already in early ages, and they also have high healthcare consultation rates for conditions other than pain. The even higher consultation rates among young females need additional attention, both in the clinic and in research. SIGNIFICANCE: We present comprehensive 1-year healthcare consultation prevalence data covering all levels of care. A significant proportion of children, adolescents and young adults consult for different pain conditions at multiple occasions warranting greater clinical awareness.

Comorbidity between pain and mental illness - Evidence of a bidirectional relationship.

BACKGROUND: Pain from various locations in the body and mental illness are common and the comorbidity between the two is well-known although the temporal relationship remains to be determined. Our aim was to follow patients over time to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an increased risk of developing mental illness (here depression/anxiety) and/or the reverse, that is whether patients with mental illness have an increased risk to develop pain or fibromyalgia, compared to the rest of the population. METHODS: This prospective cohort study used the Skåne Healthcare Register, covering all care in the region of Skåne, southern Sweden (population ~1.3 million). The cohort included healthcare consultations in primary care, outpatient specialized care and inpatient care between 2007 and 2016 for all patients without prior registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365). RESULTS: The incidence rate ratio (IRR) for developing mental illness after pain was 2.18 (95% CI = 2.14-2.22) compared to without pain. IRR for developing pain after mental illness was 2.02 (95% CI = 1.98-2.06) compared to without mental illness. Corresponding IRR for developing mental illness after fibromyalgia was 4.05 (95% CI = 3.58-4.59) and for developing fibromyalgia after mental illness 5.54 (95% CI = 4.99-6.16). CONCLUSIONS: This study shows a bidirectional influence of similar magnitude of pain and mental illness, respectively. In monitoring patients with pain or mental illness, a focus on both conditions is thus important to develop appropriate, targeted interventions and may increase the likelihood of improved outcomes. SIGNIFICANCE: We followed a population-based cohort over a period of 10 years, including incident cases of both exposure and outcome and found a bidirectional relationship between pain and mental illness. Clinicians need to pay attention on both conditions, in patients seeking care due to mental illness or pain.

Pulmonary clearance rate of two chemically different forms of inhaled pertechnetate.

Attempts to image the pulmonary deposition site of radiolabeled aerosols delivered by dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs) using single photon emission computed tomography (SPECT) have been limited by the rapid pulmonary clearance of radiolabel. To determine whether aqueous solubility of the radiolabel is a significant factor, the pulmonary clearance rates of two chemically different forms of 99mTc were calculated. A dry powder formulation of terbutaline sulphate was radiolabeled for inhalation by Turbuhaler (AstraZeneca) using the water-soluble salt sodium pertechnetate and the water-insoluble salt tetraphenylarsonium pertechnetate. A pilot study was conducted during which two control subjects each inhaled the two radiolabeled aerosols on separate days. Intrasubject clearance rates for the two species were very similar. It was therefore concluded that water insolubility of the pertechnetate salt alone was not enough to extend the lung residency time of the radiolabel.

An advanced and detailed in vitro validation procedure for the radiolabeling of carrier-free terbutaline sulphate dry powder.

The aerodynamic properties of 99mTc radiolabeled carrier-free terbutaline sulphate (TBS) have been thoroughly investigated following delivery by Turbuhaler (AstraZeneca Lund, Sweden). A full and detailed radiolabeling procedure is also reported. The in vitro radiolabel validation was performed to determine whether TBS radiolabeled in this way would be representative of the commercially available product Bricanyl Turbuhaler during clinical trials. The results indicated that variations in aerodynamic properties had been introduced and that the radiolabel would slightly underestimate the fine particle fraction of Bricanyl, but would nonetheless act as a suitable marker in vivo. Assumptions regarding the aerodynamic properties of doses likely to be received by clinical trial subjects were also examined. This has been achieved by extending the validation procedures beyond those usually reported to include dose number, time, and homogeneity dependent studies. It was found that doses extracted for testing purposes and simulated patient doses extracted shortly afterward had similar properties. Doses extracted 2 h after initial testing also had similar properties to the test doses. These results suggested that data from the test doses could be used for quality control purposes, would be representative of the doses to be received by clinical trial subjects, and that a short delay between initial testing and trial subject inhalation would be acceptable.

Cumulative and single-dose design to assess the bronchodilator effects of beta2-agonists in individuals with asthma.

With the development of different chlorofluorocarbon (CFC)-free metered dose aerosol and dry powder devices, it is necessary to study and validate the methods used for assessing and comparing their efficacy. This study evaluated the cumulative dose design by determining the bronchodilator response to salbutamol given according to either a high or a low cumulative dose regimen. Adults with asthma (n = 24) were studied in a placebo-controlled, randomized, double-blind, cross-over design. On separate days, cumulative doses of salbutamol (50+50+100+200 or 100+100+ 200+400 or 400+0+0+0 or 0+0+0+0 microg) were given via Turbuhaler with 30 min between doses. The two cumulative dose regimens produced almost identical bronchodilator responses at each time point. The relative dose-potency between the 800- and 400- microg cumulative dose regimens was 0.7 with a 95% confidence interval of 0.5-1.0, excluding the true value of 2. The 400-microg cumulative dose regimen resulted in a higher FEV1 at 115 min than the 400-microg single-dose regimen. There was no difference in the bronchodilator response to the single dose of 50, 100, or 400 microg of salbutamol after either 5 or 25 min. Thus, care should be exercised when using either a cumulative or single-dose design for comparing different beta2-agonists, or different inhalation devices, with respect to their relative dose-potency. In addition, this study provides further evidence that for short-acting beta2-agonists such as salbutamol, lower doses than those normally recommended may be used, and that repeated self-administration of low doses over a period of 60 min may give a better bronchodilator response than a single administration of a high dose.

Safety and efficacy of a high cumulative dose of salbutamol inhaled via Turbuhaler or via a pressurized metered-dose inhaler in patients with asthma.

An open, crossover and randomized study was carried out to compare the safety and efficacy of salbutamol inhaled using the dry-powder inhaler Turbuhaler, and using a pressurized metered-dose inhaler (pMDI). Twelve patients with moderate to severe asthma, aged 47-68 years, were included in the study. On two separate days, patients received a total dose of 1600 micrograms of salbutamol administered in a cumulative dose fashion: 100, 100, 200, 400 and 800 micrograms at 3-min intervals. Salbutamol inhaled via Turbuhaler caused a larger decrease in serum potassium concentration than did salbutamol inhaled via pMDI. The estimated relative dose potency of the hypokalaemic effect of salbutamol Turbuhaler vs salbutamol pMDI was 2.0 with a 95% confidence interval of 1.3-3.6. Turbuhaler caused a small (but statistically significantly greater than with pMDI) increase in heart rate, QTc interval and tremor. Blood pressure was unaffected by the treatments. No adverse events of clinical relevance were reported. The estimated relative dose potency of the bronchodilating effect (FEV1) of salbutamol Turbuhaler vs salbutamol pMDI was 3.0 with a 95% confidence interval of 1.8-5.8. In conclusion, salbutamol inhaled via Turbuhaler was more potent and seemed to have a better therapeutic ratio than salbutamol inhaled via pMDI. Both treatments were equally well tolerated.

Differences in bronchodilating potency of salbutamol in Turbuhaler as compared with a pressurized metered-dose inhaler formulation in patients with reversible airway obstruction.

Two studies are presented, with the aim of establishing the dose potency ratio for salbutamol given via Turbuhaler and via a pressurized metered-dose inhaler (pMDI). Both studies were of a double-blind, randomized design. Outpatients with mild-to-moderate chronic reversible airway obstruction were given single doses of salbutamol administered via Turbuhaler and via pMDI. Efficacy and safety variables were measured before and during 6 h after each dose. The first study was a four-way crossover study including 12 patients. The salbutamol doses given were: 50, 100 and 2x100 microg via Turbuhaler and 2x100 microg via pMDI (Ventolin). The study showed that 2x100 microg of salbutamol inhaled via Turbuhaler is more potent than 2x100 microg salbutamol inhaled via a pMDI, and that 100 microg salbutamol via Turbuhaler is at least as potent as 2x100 microg salbutamol inhaled via a pMDI. The second study including 50 patients was a placebo-controlled five-way crossover, study. Two doses of salbutamol via Turbuhaler, 50 and 2x100 microg, and via pMDI, 100 and 2x200 microg, were given. There was a dose-dependent response in forced expiratory volume in one second (FEV1) for both inhalers. Adjusted for differences in baseline FEV1 values, the estimated relative dose potency for Turbuhaler versus pMDI was 1.98:1 (95% confidence interval 12-3.2). These studies showed that the same bronchodilating effect can be achieved when half the dose of salbutamol given via a conventional pressurized metered-dose inhaler is given via Turbuhaler.

Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects.

We wanted to evaluate whether lung deposition of budesonide and terbutaline sulphate differs, and to determine lung deposition of budesonide inhaled at different peak inspiratory flows, through Turbuhaler. Lung deposition of budesonide, a lipophilic substance, and of terbutaline sulphate, a hydrophilic substance, was therefore compared, after administration via an inspiratory flow-driven, multi-dose, powder inhaler (Turbuhaler, Astra Draco AB) to 10 healthy volunteers. The radionuclide 99mTc was used to label drug particles, and radioactivity, indicating drug deposition, was measured using a gamma camera. Budesonide was inhaled at a normal flow of 58 l.min-1 and at a slow flow of 36 l-min-1. At the faster flow, a mean +/- SD 27.7 +/- 9.5% of the metered dose was deposited in the lung and at the slower flow 14.8 +/- 3.3% was deposited (p < 0.001). Mean lung deposition of terbutaline sulphate inhaled at 57 l.min-1 was 27.0 +/- 7.7%. We conclude that inspiratory flow has an important effect on lung deposition, but water solubility appears to have no effect.