Retrospective review of Surgical Availability and Readiness in 8 African countries.

OBJECTIVES: The purpose of this study was to assess surgical availability and readiness in 8 African countries using the WHO's Service Availability and Readiness Assessment (SARA) tool. SETTING: We analysed data for surgical services, including basic and comprehensive surgery, comprehensive obstetric care, blood transfusion, and infection prevention, obtained from the WHO's SARA surveys in Sierra Leone, Uganda, Mauritania, Benin, Zambia, Burkina Faso, Democratic Republic of Congo and Togo. PRIMARY AND SECONDARY OUTCOME MEASURES: Among the facilities that were expected to offer surgical services (N=3492), there were wide disparities between the countries in the number of facilities per 100 000 population that reported offering basic surgery (1.0-12.1), comprehensive surgery (0.1-0.8), comprehensive obstetric care (0.1-0.8) and blood transfusion (0.1-0.8). Only 0.1-0.3 facilities per 100 000 population had all three bellwether procedures available, namely laparotomy, open fracture management and caesarean section. In all the countries, the facilities that reported offering surgical services generally had a shortage of the necessary items for offering the services and this varied greatly between the countries, with the facilities having on average 27-53% of the items necessary for offering basic surgery, 56-83% for comprehensive surgery, 49-72% for comprehensive obstetric care and 54-80% for blood transfusion. Furthermore, few facilities had all the necessary items present. However, facilities that reported offering surgical services had on average most of the necessary items for the prevention of infection. CONCLUSIONS: There are important gaps in the surgical services in the 8 African countries surveyed. Efforts are therefore urgently needed to address deficiencies in the availability and readiness to deliver surgical services in these nations, and this will require commitment from multiple stakeholders. SARA may be used to monitor availability and readiness at regular intervals, which will enable stakeholders to evaluate progress and identify gaps and areas for improvement.

Methylglyoxal, the foe and friend of glyoxalase and Trx/TrxR systems in HT22 nerve cells.

Methylglyoxal (MGO) is a major glycating agent that reacts with basic residues of proteins and promotes the formation of advanced glycation end products (AGEs) which are believed to play key roles in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, we examined the effects of MGO on immortalized mouse hippocampal HT22 nerve cells. The endpoints analyzed were MGO and thiol status, the glyoxalase system, comprising glyoxalase 1 and 2 (GLO1/2), and the cytosolic and mitochondrial Trx/TrxR systems, as well as nuclear Nrf2 and its target genes. We found that nuclear Nrf2 is induced by MGO treatment in HT22 cells, as corroborated by induction of the Nrf2-controlled target genes and proteins glutamate cysteine ligase and heme oxygenase 1. Nrf2 knockdown prevented MGO-dependent induction of glutamate cysteine ligase and heme oxygenase 1. The cystine/glutamate antiporter, system xc(-), which is also controlled by Nrf2, was also induced. The increased cystine import (system xc(-)) activity and GCL expression promoted GSH synthesis, leading to increased levels of GSH. The data indicate that MGO can act as both a foe and a friend of the glyoxalase and the Trx/TrxR systems. At low concentrations of MGO (0.3mM), GLO2 is strongly induced, but at high MGO (0.75 mM) concentrations, GLO1 is inhibited and GLO2 is downregulated. The cytosolic Trx/TrxR system is impaired by MGO, where Trx is downregulated yet TrxR is induced, but strong MGO-dependent glycation may explain the loss in TrxR activity. We propose that Nrf2 can be the unifying element to explain the observed upregulation of GSH, GCL, HO1, TrxR1, Trx2, TrxR2, and system xc(-) system activity.

Circadian disruption and biomarkers of tumor progression in breast cancer patients awaiting surgery.

Psychological distress, which can begin with cancer diagnosis and continue with treatment, is linked with circadian and endocrine disruption. In turn, circadian/endocrine factors are potent modulators of cancer progression. We hypothesized that circadian rest-activity rhythm disruption, distress, and diurnal cortisol rhythms would be associated with biomarkers of tumor progression in the peripheral blood of women awaiting breast cancer surgery. Breast cancer patients (n=43) provided actigraphic data on rest-activity rhythm, cancer-specific distress (IES, POMS), saliva samples for assessment of diurnal cortisol rhythm, cortisol awakening response (CAR), and diurnal mean. Ten potential markers of tumor progression were quantified in serum samples and grouped by exploratory factor analysis. Analyses yielded three factors, which appear to include biomarkers reflecting different aspects of tumor progression. Elevated factor scores indicate both high levels and strong clustering among serum signals. Factor 1 included VEGF, MMP-9, and TGF-ß; suggesting tumor invasion/immunosuppression. Factor 2 included IL-1ß, TNF-α, IL-6R, MCP-1; suggesting inflammation/chemotaxis. Factor 3 included IL-6, IL-12, IFN-γ; suggesting inflammation/TH1-type immunity. Hierarchical regressions adjusting age, stage and socioeconomic status examined associations of circadian, distress, and endocrine variables with these three factor scores. Patients with poor circadian coordination as measured by rest-activity rhythms had higher Factor 1 scores (R(2)=.160, p=.038). Patients with elevated CAR also had higher Factor 1 scores (R(2)=.293, p=.020). These relationships appeared to be driven largely by VEGF concentrations. Distress was not related to tumor-relevant biomarkers, and no other significant relationships emerged. Women with strong circadian activity rhythms showed less evidence of tumor promotion and/or progression as indicated by peripheral blood biomarkers. The study was not equipped to discern the cause of these associations. Circadian/endocrine aberrations may be a manifestation of systemic effects of aggressive tumors. Alternatively, these results raise the possibility that, among patients with active breast tumors, disruption of circadian activity rhythms and elevated CAR may facilitate tumor promotion and progression.

Deficiencies in the availability of essential musculoskeletal surgical services at 883 health facilities in 24 low- and lower-middle-income countries.

BACKGROUND: The sequelae of acute musculoskeletal conditions, especially injuries and infections, are responsible for significant disability in low- and middle-income countries. This study characterizes the availability of selected musculoskeletal surgical services at different tiers of the health system in a convenience sample of 883 health facilities from 24 low- and lower-middle-income countries. METHODS: Selected data points from the World Health Organization's (WHO) tool of situational analysis of surgical availability were extracted from the WHO's database in December, 2013. These included infrastructure, physical resources and supplies, interventions, and human resources. For a descriptive analysis, facilities were divided into two groups based on number of beds (<100, 100-300, and >300) and level of facility (primary referral, secondary/tertiary, and Private/NGO/Mission). Statistical comparison was made between public and Private/NGO/Mission facilities based on number of beds (≤100, 100-300, and >300) using a Chi-Square analysis, with statistical significance at p < 0.05. FINDINGS: Significant deficiencies were noted in infrastructure, physical resources and supplies, and human resources for the provision of essential orthopedic surgical services at all tiers of the health system. Availability was significantly lower in public versus Private/NGO/Mission facilities for nearly all categories in facilities with ≤100 beds, and in a subset of measures in facilities with between 100 and 300 beds. INTERPRETATION: Deficiencies in the availability of orthopedic surgical services were observed at all levels of health facility and were most pronounced at facilities with ≤100 beds in the public sector. Strengthening the delivery of essential surgical services, including orthopedics, at the primary referral level must be prioritized if we are to reduce the burden of death and disability from a variety of emergent health conditions. FUNDING: There were no sources of funding.

The Ponseti method in the treatment of children with idiopathic clubfoot presenting between five and ten years of age.

Our goal was to evaluate the use of Ponseti's method, with minor adaptations, in the treatment of idiopathic clubfeet presenting in children between five and ten years of age. A retrospective review was performed in 36 children (55 feet) with a mean age of 7.4 years (5 to 10), supplemented by digital images and video recordings of gait. There were 19 males and 17 females. The mean follow-up was 31.5 months (24 to 40). The mean number of casts was 9.5 (6 to 11), and all children required surgery, including a percutaneous tenotomy or open tendo Achillis lengthening (49%), posterior release (34.5%), posterior medial soft-tissue release (14.5%), or soft-tissue release combined with an osteotomy (2%). The mean dorsiflexion of the ankle was 9° (0° to 15°). Forefoot alignment was neutral in 28 feet (51%) or adducted (< 10°) in 20 feet (36%), > 10° in seven feet (13%). Hindfoot alignment was neutral or mild valgus in 26 feet (47%), mild varus (< 10°) in 19 feet (35%), and varus (> 10°) in ten feet (18%). Heel-toe gait was present in 38 feet (86%), and 12 (28%) exhibited weight-bearing on the lateral border (out of a total of 44 feet with gait videos available for analysis). Overt relapse was identified in nine feet (16%, six children). The parents of 27 children (75%) were completely satisfied. A plantigrade foot was achieved in 46 feet (84%) without an extensive soft-tissue release or bony procedure, although under-correction was common, and longer-term follow-up will be required to assess the outcome.

Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.

The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.

Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A-->G promoter polymorphism.

AIM: To investigate the association of serum levels and the -2518 A-->G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus. METHODS: MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients. RESULTS: Two hundred and thirty-one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non-diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP-1 mean concentrations and percentiles were substantially higher in non-diabetic populations but were not influenced by the genotype (AA: 662.0 +/- 323.0 pg/ml; AG: 730.6 +/- 491.4 pg/ml; GG: 641.2 +/- 323.8 pg/ml). MCP-1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF-alpha and IL-6). CONCLUSIONS: This is the first study providing MCP-1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP-1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non-diabetic patients and were not related to MCP-1 levels. The mechanisms behind these elevated MCP-1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes.

Developing a free supportive care program for cancer patients within an integrative medicine clinic.

The cancer patient's journey not only includes a threat to one's life, but the need to face many medical and emotional challenges. The free Cancer Supportive Care Program (CSCP) within the Center for Integrative Medicine Clinic at Stanford University Hospital and Clinics has been identified as a successful model for helping patients to deal with these challenges. Its programs include informational lectures, support groups, chair massages, exercise, alternative modality classes, a Life Tapes Project, an informational website, and a bimonthly newsletter available free to anybody touched by cancer. Now in its third year, this program benefits from a blending of leadership resources, availability of space, institutional agreement on patient need and funds from private and corporate donations. By presenting the basic premises of the Cancer Supportive Care program and outlining specifics about the program, institutions in various national and international demographic regions may implement similar programs according to their resources and the needs of patients. It is our hope that the CSCP can become a model for the development of similar programs in various parts of the United States and abroad.

Trabecular meshwork bypass tube shunt: initial case series.

AIMS: This study describes a prospective consecutive case series of the initial six eyes of five patients undergoing implantation of the trabecular bypass tube shunt. METHODS: A prospective consecutive case series. The initial six eyes of five patients with uncontrolled open angle glaucoma who had never previously undergone ocular surgery. Implantation of the trabecular bypass tube shunt measuring 150 micro m outer diameter and 50 micro m inner diameter was performed with the distal end placed in Schlemm's canal and the proximal end in the anterior chamber. The main outcome measures were visual acuity, intraocular pressure, glaucoma medication use. RESULTS: The tube was successfully implanted in five of six eyes. In four eyes longer term follow up of 5-9 months showed no loss of visual acuity with decreased intraocular pressure from preoperative levels (mean 23.4-16.5 mm Hg) and reduced requirement of glaucoma medications (mean 3-0.5). In a subset of two eyes, there was no measured increase in aqueous flare or reduction of endothelial cell count. In one eye the tube was explanted because of presumed misplacement by excessive bleeding during surgery. Two eyes showed a diffuse bleb. CONCLUSIONS: This study reports the initial experience with a novel approach to surgical glaucoma therapy. This very small tube allows a direct communication to be established between the anterior chamber and Schlemm's canal, effecting a trabecular bypass. In this small number of eyes this procedure reduced intraocular pressure and the need for glaucoma medications without appreciable side effects.

[Nutritional workshops for cancer patients: a pilot approach]. / Les ateliers de nutrition en oncologie médicale: une expérience pilote.

The authors describe an original experience with 3 years of a nutritional workshop for cancer patients. This intervention combine an information about nutritional aspects of cancer with psychosocial support, to buffer psychological and nutritional consequences of cancer. The workshop, leaded by two specialized teams, one in medical oncology, the other in public health, is proposed to patients during and after a specific treatment. In one day, it provided information about nutrition and cancer, diet education and psychosocial support with supportive-expressive group. At this day, the evaluation of this intervention is only subjective. Fifty-six patients participated in at least one workshop, with majority of women (91%). Nineteen workshops were leaded with average participant number of 7 per workshop the third year. The authors believe that nutritional workshops are of great help for cancer patients, by enhancing social reinsertion, giving opportunity of emotional expression and humanizing the treatment. Our experience show it is possible to propose psychosocial intervention in institution in the context of Mediterranean country. We are leading currently a study that will permit a more systematic evaluation of the effects of this intervention.

Revictimization and information processing in women survivors of childhood sexual abuse.

This study examined the effect of sexual revictimization on information processing of trauma-related stimuli in a sample of child sexual abuse (CSA) survivors diagnosed with posttraumatic stress disorder (PTSD). Fifty-one treatment-seeking women participated in this study. Participants completed the Sexual Experiences Survey regarding sexual revictimization in the last 6 months and performed a modified emotional Stroop task in which they named the colors of neutral words (e.g., apple), general threat words (e.g., malignant and death), and sexual/victimization words (e.g., penis and abuser). As predicted, the revictimized participants (n = 16) took significantly longer to color-name sexual/victimization words than did the nonrevictimized participants. These results suggest that revictimization serves to prime preexisting "trauma" memory networks, thereby amplifying the impact of childhood sexual trauma on selective attention toward trauma-related stimuli.

Psychoneuroimmune and endocrine pathways in cancer: effects of stress and support.

The bulk of cancer research has productively focused on the pathophysiology of the disease, emphasizing tumor biology, especially tumor characteristics such as DNA ploidy and estrogen/progesterone receptor status as predictors of disease outcome, at the expense of studying the body's psychophysiological reactions to tumor invasion. These reactions are mediated by brain/body mechanisms, including the endocrine, neuroimmune, and autonomic nervous systems. Although a large portion of the variance in any disease outcome is accounted for by the specific local pathophysiology of that disease, some variability must also be explained by 'host resistance' factors, which include the manner of response to the stress of the illness. The evidence of links between social support, stress, emotional state, and immune and endocrine function is growing. Here we examine evidence that 2 especially promising mechanisms, one immune, one endocrine, may mediate the relationship between stress and social support on the one hand and cancer progression on the other. We chose natural killer (NK) cells and cortisol because they are particularly good examples of mediating mechanisms for which there is solid basic and clinical evidence. NK cells are of great interest because they are involved in tumor surveillance, and because their activity can be measured in vitro.

[Central retinal artery occlusion. Importance of selective intra-arterial fibrinolysis]. / Zentralarterienverschluss. Stellenwert der selektiven intraarteriellen Fibrinolyse.

BACKGROUND: Conventional treatment of a central retinal artery occlusion usually has a poor prognosis but intra-arterial fibrinolysis (IF) of the ophthalmic artery is an invasive treatment option. The importance of IF was evaluated in 62 patients with central retinal artery occlusion and in addition the risk spectrum for this disease was considered. MATERIAL AND METHODS: Data from charts of 62 patients were retrospectively analysed. Visual recovery after IF (n = 17) was compared to conventional treatment (e.g. decrease of IOP, improvement of rheological conditions, n = 45). Patients were excluded from IF if the occlusion was present for more than 8 h, if there was a history of bleeding and previous operations, or if they were older than 85 years. IF was performed using either urokinase (n = 7) or tPA (n = 10). RESULTS: Out of 62 patients, 22 (35%) with central retinal artery occlusion underwent catheterisation. Stenosis of the carotid artery excluded IF in 5 out of these 22 cases, therefore only 17 patients were treated by IF. Of the patients, 40 (65%) were excluded from IF for various reasons: 47% (19/40) arrived later than 8 h after occlusion, 17% (7/40) did not consent to IF, 15% (6/40) had medical contraindications and 13% (5/40) were over 85 years of age. Two patients required no IF because of a cilioretinal anastomosis with moderate visual acuity and another patient showed spontaneous visual recovery during ophthalmic examination. Of the 17 patients treated with IF, 4 achieved an improvement of visual acuity by more than 2 lines, no change of visual acuity was observed in 12/17 patients and 1/17 lost more than 2 lines after treatment. Of the 45 conservatively treated patients, 16 achieved improvement by more than 2 lines and no change occurred in 29/45 patients. Three patients treated with IF suffered from a stroke during treatment. The main risk factor for central retinal artery occlusion was high blood pressure in 32% of all cases and nicotine abuse in 16%. CONCLUSIONS: Many patients presented too late for IF. However, there was no statistical difference between patients with IF and conventional treatment with regards to the improvement of visual acuity. Additionally there is an increased risk of a stroke from IF, therefore a prospective study is necessary to evaluate the importance of IF. Stabilisation of high blood pressure may be the best prophylaxis for preventing a central retinal artery occlusion.

Suppression, repressive-defensiveness, restraint, and distress in metastatic breast cancer: separable or inseparable constructs?

A longstanding hypothesis links affective and behavioral inhibition with cancer incidence and progression though it does not clarify psychometric distinctions among related constructs. We hypothesized that repressive-defensiveness, suppression, restraint, and distress would be separable factors in our sample of metastatic breast cancer patients. Our results support the discriminant validity of these constructs in our total sample, and the stability over 1 year in our control group. Using factor analysis, we found 4 separate factors at our prerandomization baseline corresponding closely to hypothesized constructs. Additionally, associations in a multi-trait, multi-occasion (baseline and 1 year) matrix met each of the 3 Campbell and Fiske (1959) criteria of convergent and discriminant validity. Future research testing the links between psychological, physiological, and survival outcomes with affective inhibition in cancer patients will be clearer when informed by these distinctions.

Mind matters. Coping and cancer progression.

The idea that having an 'attitude' about cancer makes a difference in its course is a popular but controversial one. Most oncologists and surgeons believe that tumor type and stage, general health, and medical treatment are all that account for the variance in outcome. Many patients and their families believe that having the right attitude makes a difference in the course of disease. This leads us to two empirical questions: (1) Does coping make a difference in disease progression when medical prognostic variables are taken into account? and (2) What constitutes the 'right attitude'?

Supportive-expressive group therapy and distress in patients with metastatic breast cancer: a randomized clinical intervention trial.

BACKGROUND: Metastatic breast cancer carries with it considerable psychosocial morbidity. Studies have shown that some patients with metastatic breast cancer experience clinically significant anxiety and depression and traumatic stress symptoms. Supportive-expressive group psychotherapy was developed to help patients with cancer face and adjust to their existential concerns, express and manage disease-related emotions, increase social support, enhance relationships with family and physicians, and improve symptom control. METHODS: Of 125 women with metastatic breast cancer recruited into the study, 64 were randomized to the intervention and 61 to the control condition. Intervention women were offered 1 year of weekly supportive-expressive group therapy and educational materials. Control women received educational materials only. Participants were assessed at baseline and every 4 months during the first year. Data at baseline and from at least 1 assessment were collected from 102 participants during this 12-month period, and these participants compose the study population. RESULTS: Primary analyses based on all available data indicated that participants in the treatment condition showed a significantly greater decline in traumatic stress symptoms on the Impact of Event Scale (effect size, 0.25) compared with the control condition, but there was no difference in Profile of Mood States total mood disturbance. However, when the final assessment occurring within a year of death was removed, a secondary analysis showed a significantly greater decline in total mood disturbance (effect size, 0.25) and traumatic stress symptoms (effect size, 0.33) for the treatment condition compared with the control condition. CONCLUSION: Supportive-expressive therapy, with its emphasis on providing support and helping patients face and deal with their disease-related stress, can help reduce distress in patients with metastatic breast cancer.

Distress, coping, and social support among rural women recently diagnosed with primary breast cancer.

This study examined distress, coping, and group support among a sample of rural women who had been recently diagnosed with breast cancer. We recruited 100 women who had been diagnosed with primary breast cancer at one of two time points in their medical treatment: either within a window up to 3 months after their diagnosis of breast cancer, or within 6 months after completing medical treatment for breast cancer. Their mean age was 58.6 years (SD = 11.6), and 90% were of white/European American ethnicity. Women completed a battery of demographic and psychosocial measures prior to being randomized into a psychoeducational intervention study, and then again 3 months later at a follow-up assessment. The focus of this article is on the women's self-reported psychosocial status at baseline. Many of the women experienced considerable traumatic stress regarding their breast cancer. However, this distress was not reflected in a standard measure of mood disturbance that is frequently used in intervention research (the Profile of Mood States). The average woman considered her diagnosis of breast cancer to be among the four most stressful life events that she had ever experienced. Also, women on average reported a high level of helplessness/hopelessness in coping with their cancer. On average, women felt that they "often" (but not "very often") received instrumental assistance, emotional support, and informational support. Women varied considerably in which kind of social group provided them with the most support, with as many reporting that they found the greatest support in spiritual/church groups or within their family units as with breast or general cancer groups. These results suggest that among these rural women with breast cancer, distress with the diagnosis of breast cancer must be carefully assessed, as women who are highly distressed about their breast cancer may not report general mood disturbance. Furthermore, the kinds of groups that rural women with breast cancer experience as most supportive need to be identified so that psychosocial interventions can be matched to breast cancer patients' individual needs.