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.     

Understanding college student spring break drinking: Demographic considerations,perceived norms and travel characteristics

Research has documented normative perceptions of others' alcohol use and how these related to increased rates of drinking and related problems among college students. Recently, research has expanded this concept to specific events (21st birthday drinking and tailgating). No studies to date examine the construct of normative perceptions of alcohol use for spring break (SB). SB is a known time of risk for increased alcohol use, and understanding whether students overestimate SB drinking norms, variables that influence norms perceptions (gender, ethnicity and travel) and whether SB norms relate to one's own drinking can inform future prevention and intervention efforts. We extend the literature by examining SB normative perceptions: (1) whether or not these perceptions are accurate and (2) the relationship to students' own drinking and related consequences. A random sample (N?=?1583) of students were asked about their SB drinking, consequences and norm perceptions. Students' SB drinking in this study was lower than their perception of typical student SB drinking (p?<?0.001), and women's perceptions were higher than men's (p?<?0.001). After adjusting for demographics and typical drinking, SB norms were significantly associated with SB drinking among those taking a trip over SB (p?<?0.001). After controlling for SB drinking, SB drinking norms were unrelated to consequences. Similar misperceptions exist for SB drinking. Prevention and intervention efforts aimed at reducing SB drinking and consequences, particularly for those planning a trip, may incorporate SB specific social norms education.     

Slow Infusion of Low‐dose Ketamine Reduces Bothersome Side Effects Compared to Intravenous Push: A Double‐blind,Double‐dummy,Randomized Controlled Trial

Objective

We compared the analgesic efficacy and incidence of side effects when low‐dose (0.3 mg/kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over 1 minute.

Methods

This was a prospective, randomized, double‐blind, double‐dummy, placebo‐controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating scale [NRS] score ≥ 5). Patients received 0.3 mg/kg ketamine administered either as a SI or a IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference (%SPID).

Results

Fifty‐nine participants completed the study. A total of 86.2% of the IVP arm and 70.0% of the SI arm experienced any side effect (difference = 16.2%, 95% confidence interval [CI] = –5.4 to 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration—75.9% reported moderate or greater side effects versus 43.4% in the SI arm (difference = 32.5%, 95% CI = 7.9 to 57.1). Additionally, the IVP arm experienced more hallucinations (n = 8, 27.6%) than the SI arm (SI n = 2, 6.7%, difference = 20.9%, 95% CI = 1.8 to 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean %SPID values in the IVP and SI arms were 39.9 and 33.5%, respectively, with a difference of 6.5% (95% CI = –5.8 to 18.7).

Conclusion

Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia.

     

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.