Strengthening primary health care in low- and middle-income countries: furthering structural changes in the post-pandemic era.

Strengthening primary health care (PHC) is the most cost-effective approach in low- and middle-income countries (LMICs) to achieve sustainable universal health coverage (UHC), protect against health shocks, and promote health and wellbeing for all people. It has been 45 years since PHC was put on the global agenda followed by multiple efforts to advocate for more funding and improved performance of PHC. Yet, investment in PHC is still insufficient and overall performance of PHC systems is weak in LMICs, resulting in increased vulnerability and poor health outcomes especially among marginalized populations. As countries recover from the COVID-19 pandemic, which exposed the fragility of PHC platforms, it is imperative to go beyond advocacy for PHC investments and make systemic changes to strengthen PHC as the foundation of resilient and equitable health systems. We propose five gamechangers to facilitate structural changes for strengthening PHC through a focused health systems approach: (i) integration of client-centered health services at PHC level; (ii) digitization of PHC services; (iii) efficiency gains invested in essential health services; (iv) strengthening management practices for PHC at district and facility levels; and (v) advancing community engagement for PHC. To be successful, the implementation of the gamechangers must be contextualized and focus on achieving sustainable health outcomes, and therefore use implementation approaches that link essential health services to health outcomes. Through this way countries will maximize the possibility of achieving UHC and attaining the ambitious health targets of the Sustainable Development Goals (SDGs) by 2030.

[A single-case research on the impact of spending cuts on the quality of care of a regional health service].

BACKGROUND: To apply single-case research methods to evaluate the impact of the Regional Government of Galicia's spending cuts on certain aspects of the quality of healthcare. METHODS: In our study, we consider average surgical wait indicators, a Generic Healthcare Deficiency Index (GHDI) of our own design, and rates of perceived improvement based on the Healthcare Barometer. Our analysis combines bottom-up approaches (both visual inspection and non-overlapping measures) with top-down approaches (parametric techniques). RESULTS: In the quinquennial period of cutbacks, we detect several adverse impacts on the quality of healthcare. The tendency to shorten the average surgical wait is reversed and this effect is statistically significant (p<0.01), according to the three estimated ARIMA models. The GHDI increases more than before, with a total effect inferred from regression analyses by both generalized least squares, using the Cochran-Orcutt procedure with the Prais-Winsten adjustment (p<0.1), and non-linear least squares (p<0.05). Indices of perceived improvement fall in primary and specialized care, as well as in hospitalization, with the effect being moderate (NAP, non-overlap of all pairs) or large (SMD, standardized mean difference). The C statistic confirms a significant change. CONCLUSIONS: In this empirical application with single-case research techniques, we notice a certain deterioration in the analyzed indicators, which primarily affect aspects of quality that are not shielded by the doctor-patient relationship, aspects more connected to the conditions of service provision and its overall perception.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: is it justified?

Background. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. Methods. This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. Results. Median PCI was 16 (range 6–39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I–II and 17% were grade III–IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24–109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). Conclusion. Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. Trial registration researchregistry1587 (retrospectively registered) (AU)

No disponible

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei and appendix tumours in elderly patients: Is it justified?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei and appendix tumours are widespread in the world. It is unclear what should be the attitude in elderly patients. METHODS: This retrospective multicenter study collected the database from ten Spanish centers from Spanish Group of Peritoneal Cancer Surgery. The study period was between November 2002 and March 2014. Seventeen patients with age greater than or equal to 75 years with peritoneal carcinomatosis from pseudomyxoma peritonei and appendix tumours met the selection criteria for the study. Outcomes in terms of morbidity and mortality such as disease-free and overall survival were analyzed. RESULTS: Median PCI was 16 (range 6-39). Ten postoperative adverse events were detected in nine patients (44.4%). 28% were grade I-II and 17% were grade III-IV. Disease-free survival at 1 and 3 years was 67 and 44%, respectively. Overall survival at 1 and 3 years was 100 and 88%, respectively. Only cytoreduction was related to worst disease free survival after univariate (p = 0.007) and multivariate (OR 11.639, 95% CI 1.24-109.74, p = 0.03) analyses. Cytoreduction was related to the worst overall survival after univariate analysis (p = 0.046). CONCLUSION: Cytoreductive surgery and HIPEC for pseudomyxoma peritonei and appendix tumours in elderly patients it is a procedure with feasible postoperative morbi-mortality and survival outcomes. TRIAL REGISTRATION: researchregistry1587 (retrospectively registered).

Morbidity and mortality outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients aged 75 years and over: Spanish group of peritoneal cancer surgery (GECOP) multicenter study.

BACKGROUND: The aim of this study is to report the perioperative outcomes of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in patients ≥75 years from a Spanish multi-institutional experience. METHODS: This multi-institutional retrospectively analyzed a prospectively collected clinical data from 10 Spanish hospitals that are part of the Spanish Group Peritoneal Cancer Surgery (GECOP). We assessed postoperative morbidity rates and performed univariate and multivariate analyses of factors associated with overall (grade I-IV) and major (grade III-IV) postoperative morbidity. RESULTS: A total of 85 patients aged ≥75 years were included. Forty six postoperative adverse events were detected in 37 patients (43.5%). Twenty five complications in 20 patients (23.5%) were mild (grade I-II) and 16 complications in 12 patients (14.1%) were moderate-severe (grade III-IV). Five patients died in the first 90 days after the procedure (5.9%). After multivariate analysis, independent factors associated with postoperative complications were: PCI> 12 (OR: 4.14, 95% CI 1.22-14.12, p = 0.043) and the need for perioperative blood transfusion (OR: 14.91, 95% CI 3.87-57.46, p < 0.001). Regarding grade III-IV complications, after multivariate analysis, the presence of preoperative albumin levels <3.5 mgr/dl (OR: 9.15, 95% CI 1.38-60.57, p = 0.017), need for diaphragmatic peritonectomy procedures (OR: 11.32, 95% CI 1.40-91.32, p = 0.023) and perioperative blood transfusion (OR: 8.58, 95% CI 1.44-51.16, p = 0.018) were independent factors. CONCLUSIONS: Cytoreductive surgery and performing HIPEC by experienced groups in selected patients aged ≥75 years can be performed with morbidity and mortality similar to that described in the literature.

Identification, characterization and analysis of expression of genes encoding arylalkylamine N-acetyltransferases in the pea aphid Acyrthosiphon pisum.

Most organisms exhibit some kind of rhythmicity in their behaviour and/or physiology as an adaptation to the cyclical movements of the Earth. In addition to circadian rhythms, many organisms have an annual rhythmicity in certain activities, such as reproduction, migration or induction of diapause. Current knowledge of the molecular basis controlling seasonal rhythmicity, especially in insects, is scarce. One element that seems to play an essential role in the maintenance of both circadian and seasonal rhythms in vertebrates is the hormone melatonin. In vertebrates, the limiting enzyme in its synthesis is the arylalkylamine N-acetyltransferase (AANAT). Melatonin is also present in insects but the precise biochemical pathway and the enzymes involved in its synthesis are unknown. Insects possess phylogenetically distant arylalkylamine N-acetyltransferases but their involvement in melatonin synthesis still needs to be fully demonstrated. Aphids have a seasonally rhythmical life cycle, reproducing parthenogenetically by viviparity in favourable seasons but, in unfavourable seasons, they produce a single generation of sexual individuals. The length of the photoperiod is the main environmental factor that controls the mode of reproduction in aphids. Taking advantage of the availability of the genome of the aphid Acyrthosiphon pisum, we searched for genes encoding aphid arylalkylamine N-acetyltransferase homologues that could be candidates for participation in seasonal rhythmicity. We identified four AANAT genes, of which at least two (Ap-AANAT1 and Ap-AANAT3) showed highly significant variation in transcription levels depending on the photoperiod conditions. These results are discussed in the context of how seasonality can be controlled in aphids.

Síndrome de fatiga crónica: estudio de una serie consecutiva de 824 casos evaluados en dos unidades especializadas / Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units

Fundamento y objetivo. El síndrome de fatiga crónica (SFC) condiciona una importante limitación funcional. En nuestro medio se disponen de escasos estudios sobre las características del SFC, por lo que se inició el estudio de una serie consecutiva de casos diagnosticados en dos unidades especializadas. Pacientes y método. Se han incluido todos los pacientes con SFC atendidos desde enero de 2008 hasta junio de 2010. Se analizaron datos sociodemográficos y laborales, tiempo desde el inicio, factores desencadenantes y forma de inicio, criterios diagnósticos de Fukuda y canadienses, los fenómenos comórbidos y el tratamiento. Resultados. Se incluyeron 824 pacientes, 748 (91%) mujeres, con una edad media de 48±9 años. La edad media de inicio de los síntomas fue de 35±11 años, el tiempo transcurrido hasta el diagnóstico fue de 108±88 meses. En 481 pacientes (58%) se identificó un factor desencadenante y en 517 (63%) el inicio fue gradual. En 515 (62,5%) pacientes la enfermedad estaba inactiva. Entre los criterios diagnósticos de Fukuda destacó la fatiga postejercicio físico, el sueño no reparador y las alteraciones en la concentración y memoria inmediata. Los bloques sintomáticos de los criterios canadienses mostraron la uniformidad de los síntomas. Los fenómenos comórbidos acompañantes fueron: ansiedad 691 (84%), síndrome seco 678 (82%) y fibromialgia 450 (55%). Realizaban tratamiento farmacológico 520 (63%) pacientes. Conclusiones. El SFC afecta preferentemente a mujeres jóvenes, condiciona importante ausentismo laboral. Entre los criterios diagnósticos destacó la intolerancia al ejercicio físico, la disfunción neurocognitiva y el sueño no reparador. En la valoración del paciente, es muy importante la aplicación de los criterios canadienses y estudiar la comorbilidad(AU)

Background and objective. The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units. Patients and methods. We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment. Results. A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment. Conclusions. CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity(AU)

[Chronic fatigue syndrome: study of a consecutive series of 824 cases assessed in two specialized units]. / Síndrome de fatiga crónica: estudio de una serie consecutiva de 824 casos evaluados en dos unidades especializadas.

BACKGROUND AND OBJECTIVE: The chronic fatigue syndrome (CFS) is a disabling disorder. Few studies are available in our area on the prevalence and characteristics of CFS. Therefore, we carried out a study of a consecutive series of 824 cases diagnosed in two specialized units. PATIENTS AND METHODS: We evaluated all of the CFS patients seen from January 2008 to June 2010. We analyzed social and demographic data, employment status, time of clinical evolution, trigger factors and onset, Fukuda and Canadian criteria, associated comorbidities and treatment. RESULTS: A total of 824 patients were included, 748 (91%) woman, mean age 48±9 years. Average age of onset of symptoms was 35±11 years, time to diagnosis 108±88 month. A precipitating factor was identified in 481 (58%) patients, the onset was gradual in 517 (63%) and 515 (62.5%) were not employed. The most outstanding diagnostic criteria of Fukuda were prolonged generalized fatigue after exercise, sleep disturbance and impairments in concentration and short-term memory. The different groups of symptoms defined by the Canadian consensus showed that CFS is a homogeneous entity. Accompanying comorbidity phenomena were anxiety 691 (83%), sicca syndrome 678 (82%), fibromyalgia 450 (55%). A total of 63% of patients (520) received pharmacological treatment. CONCLUSIONS: CFS is an illness that preferentially affects young women and results in employment absenteeism. The most relevant clinical features were prolonged generalized fatigue after exercise, neurocognitive impairment and sleep disturbance. In the evaluation of the patient, it is very important to apply the Canadian criteria and to assess comorbidity.

Síndrome de leucoencefalopatía posterior en relación con angiopatía amiloide / Posterior leukoencephalopathy syndrome associated with amyloid angiopathy

No disponible

No disponible

Cytoreductive surgery and perioperative intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colonic origin: outcomes after 7 years' experience of a new centre for peritoneal surface malignancies

INTRODUCTION: Peritoneal carcinomatosis is a relatively frequent situation in the natural history of colorectal cancer and is associated with a dismal prognosis. Promising results have been shown after radical cytoreduction followed by intraperitoneal chemohyperthermic perfusion. The aim our study was to assess the outcomes after treating patients with peritoneal carcinomatosis of colonic origin by means of cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) followed by early postoperative intraperitoneal chemotherapy (EPIC). METHODS: Tumour resection was performed in accordance with the guidelines for oncologic surgery. Selective peritonectomies and remnant nodule electroevaporation were performed with the aim of achieving a complete cytoreduction. Peritoneal perfusion was carried out according to the Coliseum technique at 0.5-1 L/min, and chemotherapy was administered at 42oC for 40-90 min. Mitomycin C 10-12.5 mg/m(2) or oxaliplatin 360 mg/m(2) was used. Postoperative intraperitoneally administered 5-fluorouracil (5-FU) (650 mg/m(2) per day) was given for 5 consecutive days. RESULTS: Twenty patients were treated from 2001 to 2008. The mean peritoneal cancer index was 11 (range 2-39). Fifteen patients had undergone complete cytoreductive surgery. The morbidity was 40%. There was one case of death due to bone marrow aplasia. Ten patients had recurrence; five of them underwent salvage surgery. Two patients were treated with a second HIPEC. Actuarial overall survival and progression-free survival were 36% and 30% at 5 years, respectively, with a median follow-up of 18 (range 8-28) months. CONCLUSIONS: Cytoreductive surgery combined with HIPEC is a feasible technique that might increase patient survival. It represents a potential cure for selected patients who have no other alternatives (AU)

Nicotinamida adenina dinucleótido (NADH) en pacientes con síndrome de fatiga crónica / Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome

AntecedentesLa nicotinamida adenina dinucleótido (NADH) podría estar deplecionada en el síndrome de fatiga crónica. El objetivo del estudio fue evaluar la eficacia de la suplementación con NADH en estos pacientes.Material y métodosSe realizó un ensayo clínico, doble ciego, controlado con placebo de 3 meses de duración. Los pacientes fueron randomizados a NADH oral 20mg o placebo durante los 2 primeros meses. Se evaluó la intensidad de la fatiga, estado funcional, estado de ánimo, impacto funcional de la fatiga, calidad de vida, calidad del sueño, capacidad al ejercicio y reserva funcional, así como la opinión del investigador y pacientes sobre la eficacia de la intervención, antes y a los 30, 60 y 90 días del inicio del tratamiento. En la visita basal y a los 60 días (último día de tratamiento doble ciego) se realizó una prueba de esfuerzo.ResultadosSe incluyeron 86 enfermos de los cuales 77 concluyeron el estudio (edad media, 47 años; 72 mujeres). No se hallaron diferencias significativas en la mayoría de las variables estudiadas al finalizar el estudio. La administración de NADH se asoció a una disminución de estado de ansiedad de −1,0 puntos (p<0,05) y de −0,2 puntos (p=NS) en el grupo asignado a placebo. La frecuencia cardiaca máxima tras la prueba de esfuerzo disminuyó una media de −8,1l/min (p<0,05) en el grupo NADH y ascendió +1,7l/min en el grupo placebo (p=0,73). No se hallaron diferencias en la percepción de eficacia con NADH y placebo, por parte del investigador y pacientes.ConclusionesLa administración de NADH oral se asoció a una disminución de la ansiedad y de la frecuencia cardiaca máxima, tras una prueba de esfuerzo, en los pacientes con síndrome de fatiga crónica. Por el contrario, este tratamiento no modificó otras variables clínicas y el estado funcional global(AU)

BackgroundNicotinamide adenine dinucleotide (NADH) may be depleted in chronic fatigue syndrome (SFC). The purpose of the study was to evaluate the efficacy of supplementation with NADH in these patients.ResultsA total of 86 patients, 77 of whom completed the study (mean age, 47 years, 72 women) were enrolled. No significant differences were found in most of the variable studied at the end of the study. Administration of NADH was associated to a decrease in anxiety condition of −1.0 points (p<0.05) and of −0.2 points (p=NS) in the placebo assigned group. Maximum heart rate after the stress test decreased a mean of −8.1l/min (p<0.05) in the NADH group and increased by +1.7l/min in the placebo group (p=0.73). No differences were found in the perception of efficacy with NADH and placebo, by the investigator and patients.ConclusionsAdministration of oral NADH was associated to a decrease in anxiety and maximum heart rate, after a stress test in patients with CFS. On the contrary, this treatment did not modify other clinical variables and the global functional performance(AU)

[Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. / Nicotinamida adenina dinucleótido (NADH) en pacientes con síndrome de fatiga crónica.

BACKGROUND: Nicotinamide adenine dinucleotide (NADH) may be depleted in chronic fatigue syndrome (SFC). The purpose of the study was to evaluate the efficacy of supplementation with NADH in these patients. MATERIAL AND METHODS: A double blind, placebo controlled, 3 month long clinical trial was conducted. The patients were randomized to oral NADH oral 20mg or placebo during the first two months. The intensity of the fatigue, functional performance, mood state, functional impact of the fatigue, quality of life, sleep quality, exercise capacity and functional reserve as well as the investigator's and patient's opinion on the efficacy of the intervention prior to and at 30, 60 and 90 days of the onset of the treatment were evaluated. A stress test was performed in the baseline visit and at 60 days (last day of the double blind treatment). RESULTS: A total of 86 patients, 77 of whom completed the study (mean age, 47 years, 72 women) were enrolled. No significant differences were found in most of the variable studied at the end of the study. Administration of NADH was associated to a decrease in anxiety condition of -1.0 points (p<0.05) and of -0.2 points (p=NS) in the placebo assigned group. Maximum heart rate after the stress test decreased a mean of -8.1l/min (p<0.05) in the NADH group and increased by +1.7l/min in the placebo group (p=0.73). No differences were found in the perception of efficacy with NADH and placebo, by the investigator and patients. CONCLUSIONS: Administration of oral NADH was associated to a decrease in anxiety and maximum heart rate, after a stress test in patients with CFS. On the contrary, this treatment did not modify other clinical variables and the global functional performance.

La Fibromialgia es una entidad primaria del dolor. ¿Hay deterioro cognitivo en la Fibromialgia? / No disponible

No disponible

Sexual dysfunction as related to severity of fatigue in women with CFS.

To assess sexual function in women with chronic fatigue syndrome. The study included 27 women, aged 20 to 45 years, with chronic fatigue syndrome (CFS) and 15 healthy female controls. Sexual function was measured with the Golombok Rust Inventory of Sexual Satisfaction (GRISS) questionnaire and five clinical questions. In the patient group, total fatigue impact scale (FIS) score correlated with the GRISS satisfaction (r:-0.471, P < .005), avoidance (r: 0.632, P < .001) and sensuality (r: -0.445, P = .008) subscales. The GRISS satisfaction, avoidance, and sensuality subscale results and the fact of seeing the sexual act as a negative experience correlated with the intensity of fatigue in women with CFS.

Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures.

BACKGROUND: Which diagnostic procedures should be used to differentiate between idiopathic and malignant pleural effusions, is not well established. AIM: To identify which parameters allow differentiation between idiopathic and malignant pleural effusions. DESIGN: Case-note review. METHODS: Over a 12-year period, we treated 1014 consecutive pleural effusion patients, of whom 346 were diagnosed as having an idiopathic or malignant aetiology. We analysed medical history, chest X-ray, pleural fluid analysis (biochemical, microbiological and cytological), chest CT scan and additional examinations that were used according to clinical findings, and compared them with the eventual diagnosis and outcome. RESULTS: Eighty-three patients with idiopathic effusions and 263 with malignant effusions were included. Idiopathic pleural effusion resolved in 47 patients, improved in 20 and persisted in 16. Biochemical pleural fluid analysis did not predict these outcomes. A history of neoplasm, chest X-ray and CT features, as well as additional examinations according to clinical findings, established a diagnosis or suspicion of malignancy in 256 (97.7%) of the 263 patients who received a diagnosis of malignant effusion. Diagnostic thoracoscopy was helpful in seven patients in whom malignant disease was strongly suspected, despite the absence of other pathological findings. DISCUSSION: Non-invasive complementary examinations generally allowed accurate differentiation between malignant and idiopathic effusions. Patients with idiopathic pleural effusions generally had favourable outcomes.

Abdomen agudo en paciente VIH por Leishmaniasis visceral / Acute abdominal pain due to visceral Leishmaniasis in an AIDS patient

No disponible

Controversial origin of Pseudomyxoma peritonei

Pseudomyxoma peritonei describes the accumulation of mucinous material in the abdominal cavity. The main diagnostic problem appears when the primary site of origin could be appendix or ovary. In this paper describe clinicopathological features and biological markers that support appendiceal origin (AU)

Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group.

Although the negative effect of systemic steroids on bone is well documented, there is not clear evidence about possible adverse effects of inhaled steroids on bone metabolism and fractures. A cross-sectional study was performed on 105 women suffering from bronchial asthma treated with inhaled steroids and 133 controls. Bone mineral density (BMD) was measured by quantitative ultrasonography (QUS) at the calcaneus and by dual X-ray absorptiometry (DXA), at both the lumbar spine and proximal femur. Patients suffering from bronchial asthma showed no statistically significant changes in BMD as measured by DXA or QUS, compared with controls. A higher prevalence of fractures was found in the group of women with bronchial asthma, with an age-adjusted odds ratio of 2.79 (95% CI: 1.19-6.54). Inhaled steroids do not appear to decrease BMD, but are associated with an increased risk of fracture in women.