Safety and tolerability of oral daily and intermittent ibandronate are not influenced by age

OBJECTIVE: The risk of osteoporosis increases exponentially with age. Elderly patients, who are often frail, have declining functional status and take multiple medications, and require osteoporosis therapies that are not only effective, but also very well tolerated. Ibandronate is a potent nitrogen-containing bisphosphonate that can be given intermittently with extended between-dose intervals. Oral daily and intermittent ibandronate (interval between doses > 2 mo) was found to significantly reduce the risk of new morphometric vertebral fractures by 62% and 50%, respectively, compared with calcium and vitamin D supplementation alone. We investigated the effect of age on the safety profile of oral daily and intermittent ibandronate, with particular emphasis on the upper gastrointestinal (GI) safety profile of ibandronate. METHODS: A predefined subgroup analysis examined the tolerability of oral ibandronate in women aged < 70 and > or = 70 years. RESULTS: The incidence of adverse events in patients aged > or = 70 years receiving oral daily and intermittent ibandronate was similar and comparable to placebo. The incidence of upper GI adverse events, including dyspepsia and esophagitis, was also similar between the 2 treatment groups and placebo. CONCLUSION: Older patients (> or = 70 yrs) receiving oral daily and intermittent ibandronate are at no greater risk of adverse events than older patients receiving placebo. Older patients were at no greater risk of upper GI adverse events than younger patients or patients receiving placebo. As a result of the good efficacy and tolerability observed in this trial, a once-monthly oral regimen of ibandronate is in late-stage clinical development.     

Social exploitation of vitellogenin

Vitellogenin is a female-specific glucolipoprotein yolk precursor produced by all oviparous animals. Vitellogenin expression is under hormonal control, and the protein is generally synthesized directly before yolk deposition. In the honeybee (Apis mellifera), vitellogenin is not only synthesized by the reproductive queen, but also by the functionally sterile workers. In summer, the worker population consists of a hive bee group performing a multitude of tasks including nursing inside the nest, and a forager group specialized in collecting nectar, pollen, water, and propolis. Vitellogenin is synthesized in large quantities by hive bees. When hive bees develop into foragers, their juvenile hormone titers increase, and this causes cessation of their vitellogenin production. This inverse relationship between vitellogenin synthesis and juvenile hormone is opposite to the norm in insects, and the underlying proximate processes and life-history reasons are still not understood. Here we document an alternative use of vitellogenin by showing that it is a source for the proteinaceous royal jelly that is produced by the hive bees. Hive bees use the jelly to feed larvae, queen, workers, and drones. This finding suggests that the evolution of a brood-rearing worker class and a specialized forager class in an advanced eusocial insect society has been directed by an alternative utilization of yolk protein.     

A method for enzymatic dissociation of cells from isolated pancreatic islets

Summary An enzymatic method for isolation of single cells from the islets of Langerhans is described. The isolated cells appeared well preserved and survived for at least 7 days when maintained in culture. The dry mass of the isolated islet cells was found to be decreased 30 min after administration of alloxan to obese-hyperglycemic mice. Isolated individual islet cells from obese-hyperglycemic mice had a higher dry mass than those from their lean litter mates. Traduzione a cura di G. U.     

Acupuncture treatments for infantile colic: a systematic review and individual patient data meta-analysis of blinding test validated randomised controlled trials

Objective: Needle acupuncture in small children has gained some acceptance in Western medicine. It is controversial, as infants and toddlers are unable to consent to treatment. We aimed to assess its efficacy for treating infantile colic.

Design: A systematic review and a blinding-test validation based on individual patient data from randomised controlled trials. Primary end-points were crying time at mid-treatment, at the end of treatment and at a 1-month follow-up. A 30-min mean difference (MD) in crying time between acupuncture and control was predefined as a clinically important difference. Pearson’s chi-squared test and the James and Bang indices were used to test the success of blinding of the outcome assessors [parents].

Eligibility criteria and data sources: We included randomised controlled trials of acupuncture treatments of infantile colic. Systematic searches were conducted in Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, and in the Chinese language databases CNKI, VIP, Wang fang, SinoMed and Chinese Clinical Trial Registry.

Results: We included three randomised controlled trials with data from 307 participants. Only one of the included trials obtained a successful blinding of the outcome assessors in both the acupuncture and control groups. The MD in crying time between acupuncture intervention and no acupuncture control was ?24.9?min [95% confidence interval, CI ?46.2 to ?3.6; three trials] at mid-treatment, ?11.4?min [95% CI ?31.8 to 9.0; three trials] at the end of treatment and ?11.8?min [95% CI ?62.9 to 39.2; one trial] at the 4-week follow-up. The corresponding standardised mean differences [SMDs] were ?0.23 [95% CI ?0.42 to ?0.06], ?0.10 [95% CI ?0.29 to 0.08] and ?0.09 [95% CI ?0.48 to 0.30]. The heterogeneity was negligible in all analyses. The statistically significant result at mid-treatment was lost when excluding the apparently unblinded study in a sensitivity analysis: MD ?13.8?min [95%CI ?37.5 to 9.9] and SMD ?0.13 [95%CI ?0.35 to 0.09]. The registration of crying during treatment suggested more crying during acupuncture [odds ratio 7.7; 95% CI 2.7–20.6; one trial]. GRADE-Moderate quality evidence.

Conclusions: Percutaneous needle acupuncture treatments should not be recommended for infantile colic on a general basis.

Systematic review registration: PROSPERO 2015:CRD42015023253

• Key points

• The role of acupuncture in the treatment of infantile colic is controversial. Available trials are small and present conflicting results.

• There were no clinically important differences between infants receiving acupuncture and no acupuncture control in this IPD meta-analysis of randomised controlled trials.

• The data indicate that acupuncture induces some treatment pain in many of the children.

• The study results indicate that percutaneous needle acupuncture should not be recommended for treatment of infantile colic on a general basis.

     

Accounting for Attribute‐Level Non‐Attendance in a Health Choice Experiment: Does it Matter?

An extensive literature has established that it is common for respondents to ignore attributes of the alternatives within choice experiments. In most of the studies on attribute non‐attendance, it is assumed that respondents consciously (or unconsciously) ignore one or more attributes of the alternatives, regardless of their levels. In this paper, we present a new line of enquiry and approach for modelling non‐attendance in the context of investigating preferences for health service innovations. This approach recognises that non‐attendance may not just be associated with attributes but may also apply to the attribute's levels. Our results show that respondents process each level of an attribute differently: while attending to the attribute, they ignore a subset of the attribute's levels. In such cases, the usual approach of assuming that respondents either attend to the attribute or not, irrespective of its levels, is erroneous and could lead to misguided policy recommendations. Our results indicate that allowing for attribute‐level non‐attendance leads to substantial improvements in the model fit and has an impact on estimated marginal willingness to pay and choice predictions.Copyright © 2014 John Wiley & Sons, Ltd.     

Upper respiratory tract infections in general practice: diagnosis,antibiotic prescribing,duration of symptoms and use of diagnostic tests

A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.     

One-year follow-up study of patients with enterochromaffin-like cell carcinoids after treatment with octreotide long-acting release

OBJECTIVE: In a one-year study of 5 patients with chronic atrophic gastritis (CAG), pernicious anaemia (PA), hypergastrinaemia and enterochromaffin-like (ECL) cell tumours, the somatostatin analogue octreotide LAR (long-acting release) in a dose of 20 mg given intramuscularly at monthly intervals had an antiproliferative effect on the ECL cells. The aim of the present study was to follow neuroendocrine (NE) markers in the blood and macroscopic and histopathological changes in the stomach during a 12-month follow-up after discontinuation of octreotide LAR treatment. MATERIAL AND METHODS: Five patients underwent upper gastrointestinal endoscopy at 6 and 12 months' follow-up after octreotide LAR treatment. Biopsies from flat, oxyntic mucosa and from tumours were obtained. Sections were stained with haematoxylin-erythrosin and immunostained for the NE cell marker chromogranin A (CgA). Serum gastrin and CgA were measured every 3 months. RESULTS: The number of visible tumours was unchanged (7) at 12 months' follow-up. One lesion showed carcinoid tumour and the others various degrees of linear and micronodular NE hyperplasia. At the same time-point, biopsies from flat, oxyntic mucosa showed a slightly (non-significant) elevated number of CgA immunoreactive (IR) cells. Serum gastrin increased from 186+/-50 pM (mean+/-SEM) to 603+/-109 pM (normal < 40 pM); p<0.05, and serum CgA increased non-significantly from 25+/-2 ng/ml (normal < 30 ng/ml) to 61+/-11 ng/ml. CONCLUSIONS: During follow-up, slightly elevated levels of serum CgA and CgA IR cells in the oxyntic mucosa, without significant recurrence of ECL cell carcinoids, were observed.     

Peroxisome proliferator-activated receptor-gammaPro12Ala polymorphism and the association with blood pressure in type 2 diabetes: skaraborg hypertension and diabetes project

OBJECTIVE: This study explored whether the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPARgamma) is associated with blood pressure in subjects with type 2 diabetes. DESIGN: A community-based, cross-sectional observation study. SETTING: Primary care. PATIENTS: One hundred and ninety-two men and 192 women with type 2 diabetes who consecutively underwent annual follow-up. MAIN OUTCOME MEASURE: The PPARgammaPro12Ala genotype was determined by polymerase chain reaction-based techniques. Associations between genotype and blood pressure were analysed by linear regression and expressed as differences in blood pressure (delta) with 95% confidence interval (CI). RESULTS: The mean systolic blood pressure and the diastolic blood pressure were 160 mmHg (standard deviation = 22.8) and 84 mmHg (standard deviation = 9.6), respectively. Subjects with Pro/Ala (24%) or Ala/Ala (2%) had lower diastolic blood pressure (delta = 2.8; 95% CI, 0.6-5.0) when adjusted for age and gender compared with Pro/Pro subjects (74%). This association was restricted to men (delta = 4.4; 95% CI, 1.3-7.4), who also had a borderline significant difference in systolic blood pressure (delta = 6.9; 95% CI, -0.8 to 13.8). In men the difference in diastolic blood pressure remained after adjustment for age, body mass index, serum triglycerides, serum insulin and haemoglobin A(1c) (delta = 4.6; 95% CI, 1.1-8.1). A subanalysis of normotensive men (n = 100) confirmed the difference associated with the Pro12Ala polymorphism in diastolic blood pressure (delta = 5.2; 95% CI, 0.6-10.0). CONCLUSIONS: The common Pro12Ala polymorphism in PPARgamma is associated with lower diastolic blood pressure in male subjects with type 2 diabetes.