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As the population ages, spine-related pain is increasingly common in older adults. While medications play an important role in pain management, their use has limitations in geriatric patients due to reduced liver and renal function, comorbid medical problems, and polypharmacy. This review will assess the evidence basis for medications used for spine-related pain in older adults, with a focus on drug metabolism and adverse drug reactions. A PubMed/OVID search crossing common spine, neck, and back pain terms with key words for older adults and geriatrics was combined with common drug classes and common drug names and limited to clinical trials and age over 65 years. The results were then reviewed with identification of commonly used drugs and drug categories: nonsteroidal anti-inflammatories (NSAIDs), acetaminophen, corticosteroids, gabapentin and pregabalin, antispastic and antispasmodic muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol, and opioids. Collectively, 138 double-blind, placebo-controlled trials were the focus of the review. The review found a variable contribution of high-quality studies examining the efficacy of medications for spine pain primarily in the geriatric population. There was strong evidence for NSAID use with adjustments for gastrointestinal and renal risk factors. Gabapentin and pregabalin had mixed evidence for neuropathic pain. SNRIs had good evidence for neuropathic pain and a more favorable safety profile than TCAs. Tramadol had some evidence in older patients, but more so in persons aged < 65 years. Rational therapeutic choices based on geriatric spine pain diagnosis are helpful, such as NSAIDs and acetaminophen for arthritic and myofascial-based pain, gabapentinoids or duloxetine for neuropathic and radicular pain, antispastic agents for myofascial-based pain, and combination therapy for mixed etiologies. Tramadol can be well tolerated in older patients, but has risks of cognitive and classic opioid side effects. Otherwise, opioids are typically avoided in the treatment of spine-related pain in older adults due to their morbidity and mortality risk and are reserved for refractory severe pain. Whenever possible, beneficial geriatric spine pain pharmacotherapy should employ the lowest therapeutic doses with consideration of polypharmacy, potentially decreased renal and hepatic metabolism, and co-morbid medical disorders. Plain Language Summary Acetaminophen (paracetamol) is safe in older adults, but non-steroidal anti-inflammatories (e.g. ibuprofen) may be more effective for spine-related pain. Non-steroidal anti-inflammatories should be used in short-term lower dose courses with gastrointestinal precaution. Corticosteroids have the least evidence for treating nonspecific back pain. Gabapentin and pregabalin may cause dizziness or difficulty walking, but may have some benefit for neck and back nerve pain (e.g. sciatica) in older adults. They should be used in lower doses with smaller dose adjustments. Some muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine) are avoided in older adults due to risk for sedation and falls. Others (tizanidine, baclofen, dantrolene) may be helpful for neck and back pain, with the most evidence for tizanidine and baclofen. These should be used in reduced doses, avoiding tizanidine with liver disease and reducing baclofen dosing with kidney disease. Older antidepressants are typically avoided in older adults due to their side effects, but nortriptyline and desipramine may be better tolerated for neck and back nerve pain at lower doses. Overall, newer antidepressants (namely duloxetine) have a better safety profile and good efficacy for spine-related nerve pain. Tramadol may be tolerated in older adults, but has risk for sedation, upset stomach, and constipation. It may be used in lower doses after alternative medications have failed, and works well with co-administered acetaminophen. Opioids are avoided due to their side effects and mortality risk, but low-dose opioid therapy may be helpful for severe refractory pain with close monitoring of patients clinically.

In E . coli , double strand breaks (DSBs) are resected and loaded with RecA protein. The genome is then rapidly searched for a sequence that is homologous to the DNA flanking the DSB. Mismatches in homologous partners are rare, suggesting that RecA should rapidly reject mismatched recombination products; however, this is not the case. Decades of work have shown that long lasting recombination products can include many mismatches. In this work, we show that in vitro RecA forms readily observable recombination products when 16% of the bases in the product are mismatched. We also consider various theoretical models of mismatch-tolerant homology testing. The models test homology by comparing the sequences of L test bases in two single-stranded DNAs (ssDNA) from the same genome. If the two sequences pass the homology test, the pairing between the two ssDNA becomes permanent. Stringency is the fraction of permanent pairings that join ssDNA from the same positions in the genome. We applied the models to both randomly generated genomes and bacterial genomes. For both randomly generated genomes and bacterial genomes, the models show that if no mismatches are accepted stringency is ∼ 99% when L test = 14 bp. For randomly generated genomes, stringency decreases with increasing mismatch tolerance, and stringency improves with increasing L test . In contrast, in bacterial genomes when L test ∼ 75 bp, stringency is ∼ 99% for both mismatch-intolerant and mismatch-tolerant homology testing. Furthermore, increasing L test does not improve stringency because most incorrect pairings join different copies of repeats. In sum, for bacterial genomes highly mismatch tolerant homology testing of 75 bp provides the same stringency as homology testing that rejects all mismatches and testing more than ∼75 base pairs is not useful. Interestingly, in vivo commitment to recombination typically requires homology testing of ∼ 75 bp, consistent with highly mismatch intolerant testing.

We study how the quality of local business environments helps explain growth outcomes of micro- and small enterprise microfinance clients by drawing on long-term nationwide administrative data and a policy shock in Cambodia. The staggered launch of special economic zones, which we link to positive shocks to the business environment on both the demand and supply side, leads to significantly increased employment in micro- and small enterprises (MSEs) located in these special economic zones (SEZs), compared to enterprises in contextually similar districts that are unexposed to an SEZ. Key channels explaining the improved growth outcomes include expanded access to external markets for the enterprises’ goods and services, more dynamic labor environments, and improved credit terms and conditions. To broaden the relevance of our findings, we combine data from prominent empirical studies on microfinance and demonstrate how related business conditions identified in the enterprise growth literature help explain differences in client business outcomes found in their results. Policy implications are that a smaller but influential segment of microfinance borrowers significantly benefit from opportunities provided by improved local business environments and that governments and lenders can play active roles in facilitating the necessary improvements for such MSEs.Plain English SummaryFinancial access may not be fulfilling its real potential in low-income settings, unless coupled with the right opportunities in the business environment for micro- and small enterprises. We use Cambodia’s special economic zones as a policy shock to study how the quality of local business environments help explain micro- and small enterprise microfinance clients’ growth. We find that the SEZs generate large increases in employment for microfinance borrowers for both micro- and small enterprises. These increases are concentrated in locations where SEZs expand access to local markets and where there are more dynamic labor environments. The SEZs also lead the microfinance lender to improve credit terms, which contribute notably to improved enterprise outcomes. To broaden the relevance of our findings, we demonstrate how related sub-national business environment factors help explain different borrower outcomes found in extant studies that measure microfinance impacts. Policy implications are that an important subset of microfinance borrowers is able to seize opportunities provided by local business environments, and that national and subnational governments can play active roles in facilitating such improved business environments for micro and small enterprises.

Details for This Review Study Population: Adults with community-acquired pneumonia (CAP)1 Efficacy End Points: All-cause mortality; need for mechanical ventilation; rate of acute respiratory distress syndrome (ARDS); length of hospital stay Harm End Points: Hyperglycemia requiring treatment; gastrointestinal bleeding Narrative: Pneumonia is common, is associated with significant morbidity, and is a leading cause of death.2-4 In response to infection, the body generates an adaptive inflammatory response.5 Systemic corticosteroids may blunt the potentially harmful effects of this response.6-8 This review summary assesses the benefits and harms of systemic corticosteroids in hospitalized patients with CAP. All but one study used multiple-day regimens (most used seven to 10 days). [...]varying proportions of patients in each trial had chronic obstructive pulmonary disease, a condition known to benefit from corticosteroid use. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial.

“Boxed warnings” (BW), sometimes referred to as “black box warnings,” are the most serious level of warning provided by the Food and Drug Administration (FDA). We aimed to assess physician awareness and knowledge of BW, and to gain a better understanding of where physicians obtain information about serious adverse drug reactions for commonly prescribed medications. A cross-sectional survey instrument was administered to emergency medicine (EM) and pediatrician (Peds) attending and resident physicians. The main outcome measures were physician performance in identifying medications with and without black box warnings and the content of the warnings. The survey response rate was 81/198 (41 %). Respondents correctly identified medications with BW only 36.3 % of the time, but were able to correctly identify medications without such warnings 83.8 % of the time. Attending physicians were better able to identify medications with or without BW when compared with residents ( p  < 0.05). Among residents, there was a statistically significant increase in the ability to identify medications with or without BW with increasing year of training ( p  < 0.01). Correct identification of the content of BW was low in both groups (13.3 %). Only 19/50 (37 %) EM physicians and 16/31 (52 %) Peds reported that they consider BW when prescribing medications. 23/81 (29 %) respondents indicated that they did not stay current or had no method of staying current with black box information. EM and Peds attending and resident physicians at a single institution had limited ability to identify medications containing BW or the content of such warnings. A significant number reported that they did not stay current or had no consistent method for staying current with BW.

Background: Despite recent prevention gains, motor vehicle crashes continue to be the leading cause of death for US adolescents and young adults. Many of these deaths involve young unlicensed drivers that are more likely to be in fatal crashes and to engage in high-risk driving behaviors like impaired driving, speeding, and driving unrestrained. In a crash context, the influence of these high-risk behaviors may spillover to adversely affect passenger safety restraint use. Objective: To examine the effect of young unlicensed drivers on safety restraint use and mortality of their passengers. Methods. A cross-sectional analysis of the National Highway Traffic Safety Administration's Fatality Analysis Reporting System from years 1996-2008 was conducted. Fatal crashes involving unlicensed drivers (15-24 yrs) and their passengers (15-24 yrs) were included. Multivariate logistic regression with generalized estimating equations were undertaken to assess the relationship between unlicensed driving and passenger restraint use, controlling for established predictors of restraint use, including driver restraint use, passenger gender, alcohol use, number of occupants, crash year, and crash location (rural vs. urban). Results: 102,092 passengers were involved in fatal crashes nationally from 1996-2008 with 64,803 unique drivers. 6,732 (10.51%) were never licensed drivers and 5,603(8.8%) were drivers with suspended, revoked, or expired licenses. Rates of unlicensed driving ranged from 17.7% to 25.1% and increased over time. While passengers in fatal crashes averaged 40.9% restraint use, passengers of never and invalidly licensed drivers had a further decreased odds of wearing a safety restraint (OR 0.73, 95% CI 0.69-0.77, p<0.001) and (OR 0.84, 95% CI 0.79-0.90, p<0.001). Other factors related to passenger restraint use were driver restraint use (OR 15.40, 95% CI 14.71-16.11, p<0.001), being a front- seated passenger (OR 3.61, 95% CI 3.47-3.74, p<0.001), rural crash location (OR 0.71, 95% CI 0.68-0.74, p<0.001), and driver alcohol use (OR 0.74, 95% CI 0.70-0.77, p<0.001). Conclusions: We found a strong inverse correlation between unlicensed driving and passenger restraint use, suggesting a significant risk spillover effect. Unlicensed driving was involved in a disproportionate and increasing number of fatal crashes and plays a detrimental role in the lifesaving safety behaviors of their passengers. Unlicensed driving not only puts the driver and public at risk, but may also diminish passengers' ability to mitigate risk in a crash context. Our findings highlight an alarming peer influence between unlicensed drivers and passengers that has considerable implications for US highway safety and the public's health. Further in-depth study in this area can guide the development of targeted countermeasures and traffic safety programs.

We draw on mobile application data from 74 countries to document the effects of the COVID-19 pandemic on the adoption of digital finance and fintech. We estimate that the spread of COVID-19 and related government lockdowns have led to between a 24 and 32 percent increase in the relative rate of daily downloads of finance mobile applications in the sample countries. In absolute terms, this equates to an average daily increase of roughly 5.2 to 6.3 million application downloads and an aggregate increase of about 316 million app downloads since the pandemic’s outbreak to the present, taking into account prior trends. Most regions across the world exhibit notable increases in absolute, relative, and per capita terms. Preliminary analysis of country-level characteristics suggest that market size and demographics, rather than level of economic development and ex-ante adoption rates, drive differential trends.