A Nationwide Enumeration of the Surgical Workforce, its Production and Disparities in Operative Productivity in Liberia.

BACKGROUND: Any health care system that strives to deliver good health and well-being to its population relies on a trained workforce. The aim of this study was to enumerate surgical provider density, describe operative productivity and assess the association between key surgical system characteristics and surgical provider productivity in Liberia. METHODS: A nationwide survey of operation theatre logbooks, available human resources and facility infrastructure was conducted in 2018. Surgical providers were counted, and their productivity was calculated based on operative numbers and full-time equivalent positions. RESULTS: A total of 286 surgical providers were counted, of whom 67 were accredited specialists. This translated into a national density of 1.6 specialist providers per 100,000 population. Non-specialist physicians performed 58.3 percent (3607 of 6188) of all operations. Overall, surgical providers performed a median of 1.0 (IQR 0.5-2.7) operation per week, and there were large disparities in operative productivity within the workforce. Most operations (5483 of 6188) were categorized as essential, and each surgical provider performed a median of 2.0 (IQR 1.0-5.0) different types of essential procedures. Surgical providers who performed 7-14 different types of essential procedures were more than eight times as productive as providers who performed 0-1 essential procedure (operative productivity ratio = 8.66, 95% CI 6.27-11.97, P < 0.001). CONCLUSION: The Liberian health care system struggles with an alarming combination of few surgical providers and low provider productivity. Disaggregated data can provide a high-resolution picture of local challenges that can lead to local solutions.

Clean Cut (adaptive, multimodal surgical infection prevention programme) for low-resource settings: a prospective quality improvement study.

BACKGROUND: Clean Cut is an adaptive, multimodal programme to identify improvement opportunities and safety changes in surgery by enhancing outcomes surveillance, closing gaps in surgical infection prevention standards, and strengthening underlying processes of care. Surgical-site infections (SSIs) are common in low-income countries, so this study assessed a simple intervention to improve perioperative infection prevention practices in one. METHODS: Clean Cut was implemented in five hospitals in Ethiopia from August 2016 to October 2018. Compliance data were collected from the operating room focused on six key perioperative infection prevention standards. Process-mapping exercises were employed to understand barriers to compliance and identify locally driven improvement opportunities. Thirty-day outcomes were recorded on patients for whom intraoperative compliance information had been collected. RESULTS: Compliance data were collected from 2213 operations (374 at baseline and 1839 following process improvements) in 2202 patients. Follow-up was completed in 2159 patients (98·0 per cent). At baseline, perioperative teams complied with a mean of only 2·9 of the six critical perioperative infection prevention standards; following process improvement changes, compliance rose to a mean of 4·5 (P < 0·001). The relative risk of surgical infections after Clean Cut implementation was 0·65 (95 per cent c.i. 0·43 to 0·99; P = 0·043). Improved compliance with standards reduced the risk of postoperative infection by 46 per cent (relative risk 0·54, 95 per cent c.i. 0·30 to 0·97, for adherence score 3-6 versus 0-2; P = 0·038). CONCLUSION: The Clean Cut programme improved infection prevention standards to reduce SSI without infrastructure expenses or resource investments.

The role of epidemiology in informing United States childhood immunization policy and practice.

One of the ten greatest public health achievements is childhood vaccination because of its impact on controlling and eliminating vaccine-preventable diseases (VPDs). Evidence-based immunization policies and practices are responsible for this success and are supported by epidemiology that has generated scientific evidence for informing policy and practice. The purpose of this report is to highlight the role of epidemiology in the development of immunization policy and successful intervention in public health practice that has resulted in a measurable public health impact: the control and elimination of VPDs in the United States. Examples in which epidemiology informed immunization policy were collected from a literature review and consultation with experts who have been working in this field for the past 30 years. Epidemiologic examples (e.g., thimerosal-containing vaccines and the alleged association between the measles, mumps, and rubella (MMR) vaccine and autism) are presented to describe challenges that epidemiologists have addressed. Finally, we describe ongoing challenges to the nation's ability to sustain high vaccination coverage, particularly with concerns about vaccine safety and effectiveness, increasing use of religious and philosophical belief exemptions to vaccination, and vaccine hesitancy. Learning from past and current experiences may help epidemiologists anticipate and address current and future challenges to respond to emerging infectious diseases, such as COVID-19, with new vaccines and enhance the public health impact of immunization programs for years to come.

Impact of surgical infrastructure and personnel on volume and availability of essential surgical procedures in Liberia.

BACKGROUND: Essential surgical procedures rank among the most cost-effective of all healthcare interventions. The aim of this study was to enumerate surgical volumes in Liberia, quantify surgical infrastructure, personnel and availability of essential surgical procedures, describe surgical facilities, and assess the influence of human resources and infrastructure on surgical volumes. METHODS: An observational countrywide survey was done in Liberia between 20 September and 8 November 2018. All healthcare facilities performing surgical procedures requiring general, regional or local anaesthesia in an operating theatre between September 2017 and August 2018 were eligible for inclusion. Information on facility infrastructure and human resources was collected by interviewing key personnel. Data on surgical volumes were extracted from operating theatre log books. RESULTS: Of 70 healthcare facilities initially identified as possible surgical facilities, 52 confirmed operative capacity and were eligible for inclusion; all but one shared surgical data. A national surgical volume of 462 operations per 100 000 population was estimated. The median hospital offered nine of 26 essential surgical procedures. Unequal distributions of surgical infrastructure, personnel, and essential surgical procedures were identified between facilities. In multivariable regression analysis, surgical human resources (ß = 0·60, 95 per cent c.i. 0·34 to 0·87; P < 0·001) and infrastructure (ß = 0·03, 0·02 to 0·04; P < 0·001) were found to be strongly associated with operative volumes. CONCLUSION: The availability of essential surgical procedures in Liberia is extremely low. Descriptive tools can quantify inequalities, guide resource allocation, and highlight rational investment areas.

ANTECEDENTES: Los procedimientos quirúrgicos esenciales se encuentran entre los más coste-efectivos de todas las intervenciones de salud. El objetivo de este estudio fue enumerar los volúmenes quirúrgicos en Liberia, cuantificar la infraestructura quirúrgica, personal y disponibilidad de procedimientos quirúrgicos esenciales, describir las instalaciones quirúrgicas y evaluar la influencia de los recursos humanos e infraestructura en los volúmenes quirúrgicos. MÉTODOS: Se realizó una encuesta observacional a nivel nacional en Liberia entre el 20 de septiembre y 8 de noviembre de 2028. Todos los centros médicos que realizaban procedimientos quirúrgicos que precisasen anestesia general, regional o local en un quirófano entre septiembre 2017 y agosto 2018 fueron elegibles para su inclusión. La información sobre la infraestructura de las instalaciones y los recursos humanos fue recogida entrevistando a personal clave. Los datos sobre los volúmenes quirúrgicos se extrajeron de los libros de registro de quirófano. RESULTADOS: De 70 centros médicos inicialmente identificados como posibles instalaciones quirúrgicas, 52 confirmaron disponer de capacidad quirúrgica y fueron elegibles para la inclusión; todos menos uno, compartieron los datos quirúrgicos. Se estimó un volumen quirúrgico nacional de 462 operaciones por 100.000 habitantes. El hospital promedio ofrecía nueve de 26 procedimientos quirúrgicos esenciales. Se identificaron distribuciones desiguales de infraestructura quirúrgica, personal y procedimientos quirúrgicos esenciales entre los centros. Se encontró que los recursos humanos quirúrgicos (ß = 0,60, P < 0,001, i.c. del 95% 0,34-0,87) y la infraestructura (ß = 0,029, P < 0,001, i.c. del 95% 0,019-0,039) estaban fuertemente asociadas con los volúmenes quirúrgicos. CONCLUSIÓN: La disponibilidad de procedimientos quirúrgicos esenciales en Liberia es extremadamente bajo. Instrumentos descriptivos pueden cuantificar desigualdades, orientar las decisiones de asignación de recursos y destacar las áreas para una inversión racional.

The Lifebox Surgical Headlight Project: engineering, testing, and field assessment in a resource-constrained setting.

BACKGROUND: Poor surgical lighting represents a major patient safety issue in low-income countries. This study evaluated device performance and undertook field assessment of high-quality headlights in Ethiopia to identify critical attributes that might improve safety and encourage local use. METHODS: Following an open call for submissions (December 2018 to January 2019), medical and technical (non-medical) headlights were identified for controlled specification testing on 14 prespecified parameters related to light quality/intensity, mounting and battery performance, including standardized illuminance measurements over time. The five highest-performing devices (differential illumination, colour rendering, spot size, mounting and battery duration) were distributed to eight Ethiopian surgeons working in resource-constrained facilities. Surgeons evaluated the devices in operating rooms, and in a comparative session rated each headlight in terms of performance and willingness to purchase. RESULTS: Of 25 submissions, eight headlights (6 surgical and 2 technical) met the criteria for full specification testing. Scores ranged from 8 to 12 (of 14), with differential performance in lighting, mounting and battery domains. Only two headlights met the illuminance parameters of more than 35 000 lux during initial testing, and no headlight satisfied all minimum specifications. Of the five headlights evaluated in Ethiopia, daily operation logbooks noted variability in surgeons' opinions of lighting quality (6-92 per cent) and spot size (0-92 per cent). Qualitative interviews also yielded important feedback, including preference for easy transport. Surgeons sought high quality with price sensitivity (using out-of-pocket funds) and identified the least expensive but high-functioning device as their first choice. CONCLUSION: No device satisfied all the predetermined specifications, and large price discrepancies were critical factors leading surgeons' choices. The favoured device is undergoing modification by the manufacturer based on design feedback so an affordable, high-quality surgical headlight crafted specifically for the needs of resource-constrained settings can be used to improve surgical safety.

ANTECEDENTES: Una iluminación quirúrgica deficiente conlleva importantes problemas de seguridad para los pacientes en países de bajos ingresos. En Etiopía, se evaluó el rendimiento y la capacidad de iluminar el campo quirúrgico de varias lámparas de alta calidad para identificar aspectos esenciales que podrían mejorar la seguridad y fomentar su uso local. MÉTODOS: Tras una convocatoria abierta (diciembre de 2018-enero de 2019), se identificaron lamparás médicas y técnicas (no médicas) para realizar un análisis de 14 variables previamente definidas en relación con la calidad/intensidad de la luz, montaje y rendimiento de la batería, además de mediciones estandarizadas de iluminancia a largo plazo. Los cinco dispositivos de mayor rendimiento (iluminación diferencial, reproducción del color, tamaño del foco, montaje y duración de la batería) se distribuyeron entre 8 cirujanos etíopes que trabajaban en instalaciones con recursos limitados. Los cirujanos evaluaron los dispositivos en quirófano y en sesiones comparativas calificaron el rendimiento de cada lámpara y la disposición para su compra. RESULTADOS: De las 25 propuestas presentadas, 8 lámparas (6 quirúrgicas y 2 técnicas) cumplieron los criterios para realizar las pruebas de especificación completas. Las puntuaciones oscilaron entre 8 y 12 (de un total de 14), con diferencias en los ámbitos de iluminación, montaje y batería. Solo 2 lámparas proporcionaron > 35000 lux de iluminancia durante la prueba inicial, y ninguna lámpara cumplió con todas las especificaciones mínimas. De las cinco lámparas evaluadas en Etiopía, hubo una gran variabilidad en las opiniones de los cirujanos anotadas en los registros realizados, tanto sobre la calidad de la iluminación (21-92%), como del tamaño del foco (0-92%). En las entrevistas cualitativas surgieron comentarios importantes como la preferencia por un transporte fácil. Los cirujanos buscaban la mejor calidad al precio más razonable (dado que se utilizaban fondos propios para su adquisición) e identificaron el dispositivo menos costoso pero con alto funcionamiento como primera opción. CONCLUSIÓN: El hecho de que ningún dispositivo satisfizo todas las especificaciones predeterminadas y la gran variabilidad de precios fueron los aspectos esenciales que determinaron la elección de los cirujanos. El dispositivo mejor valorado está siendo modificado por el fabricante en función de los comentarios de diseño, para lograr una lámpara quirúrgica asequible y de alta calidad diseñada específicamente para satisfacer las necesidades de entornos con recursos limitados en la mejora la seguridad quirúrgica.

Variation in global uptake of the Surgical Safety Checklist.

BACKGROUND: The Surgical Safety Checklist (SSC) is a patient safety tool shown to reduce mortality and to improve teamwork and adherence with perioperative safety practices. The results of the original pilot work were published 10 years ago. This study aimed to determine the contemporary prevalence and predictors of SSC use globally. METHODS: Pooled data from the GlobalSurg and Surgical Outcomes studies were analysed to describe SSC use in 2014-2016. The primary exposure was the Human Development Index (HDI) of the reporting country, and the primary outcome was reported SSC use. A generalized estimating equation, clustering by facility, was used to determine differences in SSC use by patient, facility and national characteristics. RESULTS: A total of 85 957 patients from 1464 facilities in 94 countries were included. On average, facilities used the SSC in 75·4 per cent of operations. Compared with very high HDI, SSC use was less in low HDI countries (odds ratio (OR) 0·08, 95 per cent c.i. 0·05 to 0·12). The SSC was used less in urgent compared with elective operations in low HDI countries (OR 0·68, 0·53 to 0·86), but used equally for urgent and elective operations in very high HDI countries (OR 0·96, 0·87 to 1·06). SSC use was lower for obstetrics and gynaecology versus abdominal surgery (OR 0·91, 0·85 to 0·98) and where the common or official language was not one of the WHO official languages (OR 0·30, 0·23 to 0·39). CONCLUSION: Worldwide, SSC use is generally high, but significant variability exists. Implementation and dissemination strategies must be developed to address this variability.

ANTECEDENTES: Se ha demostrado que la utilización de la lista de verificación de seguridad quirúrgica (Surgical Safety Checklist, SSC) reduce la mortalidad y mejora el trabajo en equipo, así como el cumplimiento de las prácticas de seguridad perioperatorias. Los resultados de un trabajo piloto original se publicaron hace 10 años. El objetivo de este estudio fue determinar la prevalencia actual y los predictores de uso de la SSC a nivel mundial. MÉTODOS: Se analizaron los datos agrupados de los estudios GlobalSurg y Surgical Outcomes para describir la utilización de la SSC entre 2014-2016. La principal variable de exposición fue el índice de desarrollo humano (Human Development Index, HDI) del país informante y la principal variable de resultado, la tasa de utilización de la SCC. Para determinar las diferencias en la utilización de la SSC por paciente, centro y características nacionales se utilizó una ecuación de estimación generalizada con conglomerados por centros. RESULTADOS: Se incluyeron 85.957 pacientes de 1.464 centros en 94 países. La tasa media de utilización de la SSC fue del 75,4% de las operaciones. Al compararlos con países de HDI muy alto, la utilización de la SCC fue menor en los países con HDI bajo (razón de oportunidades, odds ratio, OR 0,08, i.c. del 95% 0,05-0,12). En países con HDI bajo, la SSC se utilizó menos en operaciones urgentes en comparación con operaciones electivas (OR 0,68, i.c. del 95% 0,53- 0,86) a diferencia de los países con HDI elevado, en los que se utilizó por igual en ambas situaciones (OR 0,96, i.c. del 95% 0,87-1,06). La utilización de la SSC fue menor en operaciones de obstetricia y ginecología que en cirugía abdominal (OR 0,91, i.c. del 95% 0,85 a 0,98) y en aquellos países en los que el idioma habitual u oficial era diferente a los idiomas oficiales de la OMS (OR 0,30, i.c. del 95% 0,23 a 0,39). CONCLUSIÓN: A nivel mundial, el uso de SSC en general es alto, pero existe una variabilidad significativa. Se deben desarrollar estrategias de implementación y difusión para resolver esta variabilidad.

Evaluating the collection, comparability and findings of six global surgery indicators.

BACKGROUND: In 2015, six indicators were proposed to evaluate global progress towards access to safe, affordable and timely surgical and anaesthesia care. Although some have been adopted as core global health indicators, none has been evaluated systematically. The aims of this study were to assess the availability, comparability and utility of the indicators, and to present available data and updated estimates. METHODS: Nationally representative data were compiled for all World Health Organization (WHO) member states from 2010 to 2016 through contacts with official bodies and review of the published and grey literature, and available databases. Availability, comparability and utility were assessed for each indicator: access to timely essential surgery, specialist surgical workforce density, surgical volume, perioperative mortality, and protection against impoverishing and catastrophic expenditure. Where feasible, imputation models were developed to generate global estimates. RESULTS: Of all WHO member states, 19 had data on the proportion of the population within 2h of a surgical facility, 154 had data on workforce density, 72 reported number of procedures, and nine had perioperative mortality data, but none could report data on catastrophic or impoverishing expenditure. Comparability and utility were variable, and largely dependent on different definitions used. There were sufficient data to estimate that worldwide, in 2015, there were 2 038 947 (i.q.r. 1 884 916-2 281 776) surgeons, obstetricians and anaesthetists, and 266·1 (95 per cent c.i. 220·1 to 344·4) million operations performed. CONCLUSION: Surgical and anaesthesia indicators are increasingly being adopted by the global health community, but data availability remains low. Comparability and utility for all indicators require further resolution.

Evaluation of an adult immunization composite measure in the Indian Health Service.

BACKGROUND: Government agencies, healthcare accreditation bodies and quality improvement organizations support the development of new quality measures. Composite quality measures use more than one measure to develop a broader assessment of healthcare system function. Currently, no composite measures for adult immunization coverage exist. Development of such measures could facilitate improvements in adult immunization coverage by focusing on measurement of receipt of all age-recommended vaccines. METHODS: We recruited five Indian Health Service (IHS) and Tribal health clinics to pilot an Adult Immunization Composite Measure (AICM). Data were collected monthly over seven months using a pre-programmed electronic health record (EHR) reporting tool (IHS sites); Tribal sites used third-party software or a programmable EHR reporting function. Data collected included: number of adults aged 19 years and over who were active users of the facility with at least two visits in the last three years; the cumulative number fully immunized per age-based recommendations for tetanus toxoid-containing vaccines, pertussis, zoster and pneumococcal vaccines; and the percent immunized for the AICM and for each individual vaccine. Coverage was calculated for three age groups: 19-59 years; 60-64 years; and 65 years and older. RESULTS: All sites reported aggregate immunization data monthly from patient EHR records. For all adults 19 years and older, AICM coverage ranged from 49% to 87% at the end of the report period. Two sites showed increases in AICM coverage ≥ 3%. Improvements in zoster vaccine coverage accounted for most of the increase observed. One site specifically focused on improving zoster coverage as a result of using the AICM. CONCLUSIONS: We demonstrated the feasibility of implementing a composite measure of adult immunization coverage. This is the first measure capable of monitoring immunization completeness, coverage improvement and overall adult vaccine program effectiveness for adults who receive all recommended, age-based vaccines.

Efficacy and safety of a fixed-dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction.

BACKGROUND: Ibuprofen is an effective analgesic treatment with a ceiling effect at doses above 400 mg. This study compared the combination of ibuprofen 400 mg and caffeine 100 mg with ibuprofen 400 mg monotherapy, caffeine and placebo in the analgesic treatment of moderate to severe acute dental pain following third molar extraction. METHODS: Phase III, active-/placebo-controlled, double-blind, single-centre, two-stage, parallel-group study in adult patients with at least moderate baseline pain intensity. Primary endpoint was defined as the time-weighted sum of pain relief and pain intensity difference over 8 h (SPRID0-8 h), secondary endpoints included duration of pain relief, time to meaningful pain relief and more. RESULTS: N = 748 patients were enrolled and N = 562 treated. Mean baseline pain intensity was 7.7 on a 0-10 numerical rating scale. Analysis of SPRID0-8 h demonstrated superior analgesic effects for a single dose of ibuprofen/caffeine versus ibuprofen, caffeine and placebo over 8 h, rescue medication in this stage was requested by more patients on ibuprofen (32.5%) than on ibuprofen/caffeine (16.0%). Median time to meaningful pain relief was shorter for ibuprofen/caffeine (1.13 h) compared with ibuprofen (1.78 h; p = 0.0001). More patients on ibuprofen/caffeine than on ibuprofen reported meaningful pain relief. Adverse events were infrequent and mostly mild or moderate across treatment groups. Tolerability was rated as 'very good' or 'excellent' by most patients in both treatment groups. CONCLUSION: This study demonstrated clinically relevant superiority of ibuprofen/caffeine over monotherapy with ibuprofen in patients with acute dental pain. All treatments were well tolerated. SIGNIFICANCE: This trial showed superior efficacy of 400/100 mg ibuprofen/caffeine, compared to 400 mg ibuprofen alone, for treating acute pain, reflecting that caffeine is an effective analgesic adjuvant. Data on efficacy of 400 mg ibuprofen combined with caffeine for the treatment of acute pain were not available yet.

Efficacy and safety of nicoboxil/nonivamide ointment for the treatment of acute pain in the low back - A randomized, controlled trial.

BACKGROUND: Until now, nonivamide/nicoboxil ointment has not been tested in a randomized trial for the treatment of acute non-specific low back pain. METHODS: This phase III randomized, double-blind, active- and placebo-controlled, multi-centre trial investigated efficacy, safety and tolerability of topical nicoboxil 2.5%/nonivamide 0.4% for treatment of acute non-specific low back pain [primary endpoint: pain intensity (PI) difference between pre-dose baseline and 8 h after the first application]. RESULTS: Patients (n = 805), 18-74 years of age were treated for up to 4 days with nicoboxil 2.5%/nonivamide 0.4%, nicoboxil 2.5%, nonivamide 0.4% or placebo ointment. Pre-dose baseline pain intensity (6.6 on a 0- to 10-point numerical rating scale) was reduced by 1.049 points with placebo, by 1.428 points with nicoboxil, by 2.252 points with nonivamide and by 2.410 points with nicoboxil/nonivamide after 8 h (p < 0.0001 for nicoboxil/nonivamide vs. placebo, nicoboxil; p = 0.4171 for nicoboxil/nonivamide vs. nonivamide). At the end of treatment, the combination provided more pronounced PI reduction (3.540 points) compared with nicoboxil (2.371, p < 0.0001), nonivamide (3.074, p = 0.0259) and placebo (1.884, p < 0.0001). Low back mobility scores on Day 1 were better for the combination compared with all other treatments (p < 0.044); on Day 2-4, scores were better than for placebo and nicoboxil (p < 0.003). Patients assessed efficacy of the combination as greater than of the comparators (p ≤ 0.0129). All treatments were tolerated well. No treatment-related serious adverse events were reported. CONCLUSION: Nicoboxil/nonivamide ointment is an effective, well-tolerated medication for the treatment of acute non-specific low back pain.

Topical ambroxol for the treatment of neuropathic pain. An initial clinical observation.

BACKGROUND: Neuropathic pain is difficult to treat, and the available options are often inadequate. The expectorant ambroxol also acts as a strong local anaesthetic and blocks sodium channels about 40 times more potently than lidocaine. It preferentially inhibits the channel subtype Nav 1.8, which is expressed especially in nociceptive C-fibres. In view of the low toxicity of ambroxol, it seemed reasonable to try using it for the treatment of neuropathic pain that failed to respond to other standard options. MATERIAL AND METHODS: The medical records of seven patients with severe neuropathic pain and pain reduction following topical ambroxol treatment are reported retrospectively. As standard therapies had not proved sufficient, a topical ambroxol 20% cream was repeatedly applied by the patients in the area of neuropathic pain. RESULTS: The reasons for neuropathic pain were postherpetic neuralgia (2 ×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and foot neuropathy of unknown origin. The individual mean pain intensity reported was between 4 and 6/10 (NRS), maximum pain at 6-10/10 (NRS). The pain reduction achieved individually following ambroxol cream was 2-8 points (NRS) within 5-30 min and lasted for 3-8 h. Pain attacks were reduced in all five patients presenting with this problem. Four patients with no improvement after lidocaine 5% and one patient with no response to capsaicin 8% nevertheless experienced a pain reduction with topical ambroxol. No patient reported any side effects or skin changes during a treatment that has since been continued for up to 4 years. CONCLUSION: Ambroxol acts as a strong local anaesthetic and preferentially inhibits the nociceptively relevant sodium channel subtype Nav 1.8. For the first time, we report below on a relevant pain relief following topical ambroxol 20% cream in patients with neuropathic pain. In view of the positive side effect profile, the clinical benefit in patients with pain should be investigated further.

[Topical ambroxol for the treatment of neuropathic pain: A first clinical observation. German version]. / Topisches Ambroxol zur Behandlung neuropathischer Schmerzen: Eine erste klinische Beobachtung.

BACKGROUND: Neuropathic pain is difficult to treat and available options are frequently not sufficient. The expectorant ambroxol also works as a strong local anesthetic and blocks sodium channels about 40 times more potently than lidocaine. Ambroxol preferentially inhibits the channel subtype Nav 1.8, which is expressed particularly in nociceptive C fibers. Due to the low toxicity, topical ambroxol seemed to represent a reasonable therapeutic attempt for treatment of neuropathic pain resistant to other standard options. MATERIALS AND METHODS: Medical records of 7 patients with severe neuropathic pain, in whom many attempts at treatment with approved substances were not sufficient or possible, are reported retrospectively. Patients were then treated with topical ambroxol 20% cream applied in the area of neuropathic pain. RESULTS: Causes of neuropathic pain were postherpetic neuralgia (2-×), mononeuropathy multiplex, phantom pain, deafferentation pain, postoperative neuralgia and an unclear allodynia of the foot. Mean pain intensity was reported as 4-6/10 on a numeric rating scale (NRS) and maximum pain intensity as 6-10/10. Pain reduction following ambroxol cream was 2-8 points (NRS) within 15-30 min and lasted 3-8 h. Pain attacks were reduced in all 5 patients presenting this problem. Topical ambroxol achieved pain reduction in 4 patients with no improvement after lidocaine 5% and 1 patient with no response to capsaicin 8%. No adverse events or skin changes have been observed, and the longest treatment duration is currently 4 years. CONCLUSION: Ambroxol acts as a strong local anesthetic and preferentially inhibits the nociceptive-relevant sodium channel subtype Nav 1.8. For the first time, we report relevant pain reduction following topical Ambroxol 20% cream in patients with neuropathic pain. Regarding the advantageous profile with rare side effects, the clinical benefit for pain patients should be further investigated.

Surgically avertable burden of obstetric conditions in low- and middle-income regions: a modelled analysis.

OBJECTIVE: To quantify the burden of maternal and neonatal conditions in low- and middle-income countries (LMICs) that could be averted by full access to quality first-level obstetric surgical procedures. DESIGN: Burden of disease and epidemiological modelling. SETTING: LMICs from all global regions. POPULATION: The entire population in 2010. METHODS: We included five conditions in our analysis: maternal haemorrhage; obstructed labour; obstetric fistula; abortion(1) ; and neonatal encephalopathy. Demographic and epidemiological data were obtained from the Global Burden of Disease 2010 study. We split the disability-adjusted life years (DALYs) of these conditions into surgically 'avertable' and 'non-avertable' burdens. We applied the lowest age-specific fatality rates from all global regions to each LMIC region to estimate the avertable deaths, assuming that the differences of death rates between each region and the lowest rates reflect the gap in surgical care. MAIN OUTCOME MEASURES: Deaths and DALYs avertable. RESULTS: Of the estimated 56.6 million DALYs (i.e. 56.6 million years of healthy life lost) of the selected five conditions, 21.1 million DALYs (37%) are avertable by full coverage of quality obstetric surgery in LMICs. The avertable burden in absolute term is substantial given the size of burden of these conditions in LMICs. Neonatal encephalopathy constitutes the largest portion of avertable burden (16.2 million DALYs) among the five conditions, followed by abortion (2.1 million DALYs). CONCLUSIONS: Improving access to quality surgical care at first-level hospitals could reduce a tremendous burden of maternal and neonatal conditions in LMICs.

Evaluation of a large-scale donation of Lifebox pulse oximeters to non-physician anaesthetists in Uganda.

Pulse oximetry is widely accepted as essential monitoring for safe anaesthesia, yet is frequently unavailable in resource-limited settings. The Lifebox pulse oximeter, and associated management training programme, was delivered to 79 non-physician anaesthetists attending the 2011 Uganda Society of Anaesthesia Annual Conference. Using a standardised assessment, recipients were tested for their knowledge of oximetry use and hypoxia management before, immediately following and 3-5 months after the training. Before the course, the median (IQR [range]) test score for the anaesthetists was 36 (34-39 [26-44]) out of a maximum of 50 points. Immediately following the course, the test score increased to 41 (38-43 [25-47]); p < 0.0001 and at the follow-up visit at 3-5 months it was 41 (39-44 [33-49]); p = 0.001 compared with immediate post-training test scores, and 75/79 (95%) oximeters were in routine clinical use. This method of introduction resulted in a high rate of uptake of oximeters into clinical practice and a demonstrable retention of knowledge in a resource-limited setting.

Effect of hyoscine butylbromide (Buscopan®) on cholinergic pathways in the human intestine.

BACKGROUND: Hyoscine butylbromide (HBB, Buscopan(®) ) is clinically used to treat intestinal cramps and visceral pain. Various studies, mainly on animal tissues, suggested that its antimuscarinic action is responsible for its spasmolytic effect. However, functional in vitro studies with human tissue have not been performed so far. METHODS: We wanted to provide a comprehensive study on the mode of action of HBB in human intestinal samples and investigated HBB (1 nmol L(-1) -10 µmol L(-1)) effects on muscle activity with isometric force transducers and calcium imaging, on epithelial secretion with Ussing chamber technique and on enteric neurons using fast neuroimaging. KEY RESULTS: Hyoscine butylbromide concentration dependently reduced muscle contractions, calcium mobilization, and epithelial secretion induced by the muscarinic agonist bethanechol with IC50 values of 429, 121, and 224 nmol L(-1), respectively. Forskolin-induced secretion was not altered by HBB. Cholinergic muscarinic muscle and epithelial responses evoked by electrical nerve stimulation were inhibited by 1-10 µmol L(-1) HBB. Moreover, HBB significantly reduced the bethanechol-induced action potential discharge in enteric neurons. Interestingly, we observed that high concentrations of HBB (10 µmol L(-1)) moderately decreased nicotinic receptor-mediated secretion, motility, and nerve activity. CONCLUSIONS & INFERENCES: The results demonstrated the strong antimuscarinic action of HBB whereas the nicotinic antagonism at higher concentrations plays at most a moderate modulatory role. The muscle relaxing effect of HBB and its inhibition of muscarinic nerve activation likely explain its clinical use as an antispasmodic drug. Our results further highlight a so far unknown antisecretory action of HBB which warrants further clinical studies on its use in secretory disorders.

A label-free, impedance-based real time assay to identify drug-induced toxicities and differentiate cytostatic from cytotoxic effects.

Cell-based assays are key tools in drug safety assessment. However, they usually provide only limited information about time-kinetics of a toxic effect and implementing multiple measurements is often complex. To overcome these issues we established an impedance-based approach which is able to differentiate cytostatic from cytotoxic drugs by recording time-kinetics of compound-effects on cells. NIH 3T3 fibroblasts were seeded on xCELLigence® E-plates and impedance was continuously measured over 5 days. The obtained results reflected cytotoxicity and cell proliferation, as confirmed by neutral red uptake in vitro. Based on known toxicants, we established an algorithm able to discriminate cytostatic, cytotoxic and non-toxic compounds based on the shape of the impedance curves. Analyzing impedance curve patterns of additional 37 compounds allowed the identification and differentiation of these distinct effects as results correlated well with previous in vivo findings. We show that impedance-based real-time cell analysis is a convenient tool to characterize and discriminate effects of compounds on cells in a time-dependent and label-free manner. The presented impedance assay could be used to further characterize toxicities observed in vivo or in vitro. Due to the ease of performance it may also be a suitable screening tool.