Gabapentinoids and Acetaminophen as Adjuvants for Managing Postoperative Pain.

With the current opiate epidemic in the United States, there is renewed interest in evaluating non-opiate adjuvant medications as effective alternatives for the prevention and treatment of postoperative pain. A systematic review of randomized, controlled trials on Pub Med, Medline, and Embase was conducted looking on postoperative pain management from 2008 to 2018. Studies were included if they used a gabapentenoid with or without acetaminophen and evaluated supplemental opiate use. All adult (18 years or older) surgical populations were considered for inclusion, and fourteen clinical trials met inclusion criteria. Gabapentenoid dosing varied among studies. In nine of fourteen studies, there was a finding of superiority as compared to placebo in managing postoperative pain and decreasing supplemental opiate use. Pregabalin was used in twelve of the fourteen studies and gabapentin was used in two of the fourteen studies. Of the nine studies that found a benefit from using a gabapentoid, all included pregabalin. While the rate of adverse effects was low in all studies, it was found to increase as dosages increased. Results support that pregabalin has a role in decreasing postoperative pain intensity and supplemental opiate use; however, the optimal dose or dosing regimen is not yet well understood.

Measurement of Diacetyl and Related Compounds in Coffee Roasteries and Breweries.

α-Diketones such as diacetyl (2,3-butanedione) and 2,3-pentanedione are generated during the roasting and fermentation of foods and are also used as flavoring compounds. Exposure to these compounds has been associated with obliterative bronchiolitis in workers. We report indoor air concentrations of diacetyl and 2,3-pentanedione, as well as acetoin (3-hydroxy-2-butanone), in several small coffee roasteries and breweries using standard integrated air sampling sorbent tubes followed by gas chromatography tandem mass spectrometry as well as the first use of on-site continuous real-time proton-transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). Diacetyl and 2,3-pentanedione were detected in most of the sorbent samples at concentrations between 0.02 and 8 ppbv, and in general were higher in coffee roasteries compared with breweries. Three integrated air samples, all from the barista area at one facility, exceeded the NIOSH recommended exposure limit (REL) of 5 ppbv for diacetyl. 2,3-Pentanedione concentrations in these three samples were greater than 50% of its REL, but did not exceed it. Acetoin, a precursor to diacetyl, was also detected at concentrations between 0.03 and 5 ppbv in most sorbent tube samples, with concentrations generally higher in breweries. PTR-ToF-MS measurements exhibited similar trends and provided continuous real-time volatile organic compound data that showed episodic excursions with peak concentrations of diacetyl and 2,3-pentanedione between 15 and 20 ppbv. Examination of the time series data identified specific activities associated with peak diketone emissions, including transfer of freshly roasted coffee beans to the cooling tray, or the opening of a brew kettle. Additional indoor air quality parameters including CO2, NO2, and PM2.5 were also assessed on-site. Airway inflammation was assessed in 19 workers before and after each work shift using online measurements of fractional exhaled nitric oxide (FENO). The pre-shift mean FENO was 3.7 (95% confidence interval: -3.6, 11.0) ppbv higher and the post-shift FENO was 7.1 (-1.9, 16.1) ppbv higher for workers at coffee roasteries compared with breweries. The cross-shift change in FENO was 3.4 (-2.8, 9.6) ppbv higher for workers at coffee roasteries compared with breweries. However, none of these differences were statistically significant, and the cross-shift change in FENO was not statistically different from zero for either group of workers. The findings from this pilot study demonstrate that α-diketones and related compounds are present in the indoor air of both breweries and coffee roasteries and may exceed health protective guidelines in coffee roasteries. Additional studies are required to fully characterize worker exposures in these settings and to identify specific work activities and processes associated with high exposures. Engineering controls, including targeted exhaust ventilation and the use of low-cost sensors, are recommended as an approach to protect workers from exposure to hazardous levels of α-diketones.

Can traditional birth attendants be trained to accurately identify septic infants, initiate antibiotics, and refer in a rural African setting?

BACKGROUND: Neonatal sepsis is a major cause of neonatal mortality. In populations with limited access to health care, early identification of bacterial infections and initiation of antibiotics by community health workers (CHWs) could be lifesaving. It is unknown whether this strategy would be feasible using traditional birth attendants (TBAs), a cadre of CHWs who typically have limited training and educational backgrounds. METHODS: We analyzed data from the intervention arm of a cluster-randomized trial involving TBAs in Lufwanyama District, Zambia, from June 2006 to November 2008. TBAs followed neonates for signs of potential infection through 28 days of life. If any of 16 criteria were met, TBAs administered oral amoxicillin and facilitated referral to a rural health center. RESULTS: Our analysis included 1,889 neonates with final vital status by day 28. TBAs conducted a median of 2 (interquartile range 2-6) home visits (51.4% in week 1 and 48.2% in weeks 2-4) and referred 208 neonates (11%) for suspected sepsis. Of referred neonates, 176/208 (84.6%) completed their referral. Among neonates given amoxicillin, 171/183 (93.4%) were referred; among referred neonates, 171/208 (82.2%) received amoxicillin. Referral and/or initiation of antibiotics were strongly associated with neonatal death (for referral, relative risk [RR] = 7.93, 95% confidence interval [CI] = 4.4-14.3; for amoxicillin administration, RR = 4.7, 95% CI = 2.4-8.7). Neonates clinically judged to be "extremely sick" by the referring TBA were at greatest risk of death (RR = 8.61, 95% CI = 4.0-18.5). CONCLUSION: The strategy of administering a first dose of antibiotics and referring based solely on the clinical evaluation of a TBA is feasible and could be effective in reducing neonatal mortality in remote rural settings.

Bottlenecks, barriers, and solutions: results from multicountry consultations focused on reduction of childhood pneumonia and diarrhoea deaths.

Millions of children still die unnecessarily from pneumonia and diarrhoea, mainly in resource-poor settings. A series of collaborative consultations and workshops involving several hundred academic, public health, governmental and private sector stakeholders were convened to identify the key barriers to progress and to issue recommendations. Bottlenecks impairing access to commodities included antiquated supply management systems, insufficient funding for drugs, inadequate knowledge about interventions by clients and providers, health worker shortages, poor support for training or retention of health workers, and a failure to convert national policies into action plans. Key programmatic barriers included an absence of effective programme coordination between and within partner organisations, scarce financial resources, inadequate training and support for health workers, sporadic availability of key commodities, and suboptimal programme management. However, these problems are solvable. Advocacy could help to mobilise needed resources, raise awareness, and prioritise childhood pneumonia and diarrhoea deaths in the coming decade.

Training Zambian traditional birth attendants to reduce neonatal mortality in the Lufwanyama Neonatal Survival Project (LUNESP).

OBJECTIVE: To provide relevant details on how interventions in the Lufwanyama Neonatal Survival Project (LUNESP) were developed and how Zambian traditional birth attendants (TBAs) were trained to perform them. METHODS: The study tested 2 interventions: a simplified version of the American Academy of Pediatrics' neonatal resuscitation protocol (NRP); and antibiotics with facilitated referral (AFR). RESULTS: Key elements that enabled the positive study result were: focusing on common and correctible causes of mortality; selecting a study population with high unmet public health need; early community mobilization to build awareness and support; emphasizing simplicity in the intervention technology and algorithms; using a traditional training approach appropriate to students with low literacy rates; requiring TBAs to demonstrate their competence before completing each workshop; and minimizing attrition of skills by retraining and reassessing the TBAs regularly throughout the study. CONCLUSION: An effective NRP training model was created that is suitable for community-based neonatal interventions, in research or programmatic settings, and by practitioners with limited obstetric skills and low rates of literacy. Clinicaltrials.gov NCT00518856.

Costs and cost-effectiveness of training traditional birth attendants to reduce neonatal mortality in the Lufwanyama Neonatal Survival study (LUNESP).

BACKGROUND: The Lufwanyama Neonatal Survival Project ("LUNESP") was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. METHODS AND FINDINGS: We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011-2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as 'conservative' and 'optimistic' scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. CONCLUSIONS: Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was 'highly cost effective'. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care.

Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study.

OBJECTIVE: To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. DESIGN: Prospective, cluster randomised and controlled effectiveness study. SETTING: Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers' homes, in rural village settings. PARTICIPANTS: 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. INTERVENTIONS: Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). MAIN OUTCOME MEASURES: The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. RESULTS: Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by intervention birth attendants (0.37, 0.17 to 0.81) and by 81% within the first two days after birth (0.19, 0.07 to 0.52). Stillbirths and deaths from serious infection occurred at similar rates in both groups. CONCLUSIONS: Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting. This approach has high potential to be applied to similar settings with dispersed rural populations. Trial registration Clinicaltrials.gov NCT00518856.

Barriers to adherence to antiretroviral medications among patients living with HIV in southern China: a qualitative study.

Although China's government is rapidly expanding access to antiretroviral therapy, little is known about barriers to adherence among Chinese HIV-infected patients, particularly among injection drug users. To better understand barriers to antiretroviral treatment adherence, we conducted a qualitative research study, using both focus group and key informant methods, among 36 HIV-positive men and women in Dali, in southwestern China. All interviews utilized semi-structured question guides and were conducted in Mandarin, audio-recorded and translated into English for analysis. The most commonly cited adherence challenges were stigma, including secondary stigma experienced by family members; mental health issues; and economic concerns, particularly related to finding and maintaining employment. Distinctive gender differences emerged, partly due to previous heroin use among male respondents. Optimizing adherence may require that antiretroviral therapy programs be linked to other services, including drug addiction treatment, mental health services and vocational treatment and support. HIV care and service providers and policy makers in China responsible for HIV treatment should be aware of these important barriers to adherence.

Asymmetric total synthesis of the proposed structure of the medicinal alkaloid jamtine using the chiral base approach.

[reaction: see text] A highly step-economic asymmetric synthesis of the tetracyclic structure assigned to the medicinal alkaloid jamtine has been accomplished using a chiral lithium amide base desymmetrization of a ring-fused imide. The structure synthesized appears to be different from that of the natural product originally reported.