Examining treatment targets and equity in bone-active medication use within secondary fracture prevention: a systematic review and meta-analysis.

PURPOSE: This systematic review seeks to evaluate the proportion of fragility fracture patients screened in secondary fracture prevention programs who were indicated for pharmacological treatment, received prescriptions for bone-active medications, and initiated the prescribed medication. Additionally, the study aims to analyze equity in pharmacological treatment by examining equity-related variables including age, sex, gender, race, education, income, and geographic location. METHODS: We conducted a systematic review to ascertain the proportion of fragility fracture patients indicated for treatment who received prescriptions and/or initiated bone-active medication through secondary fracture prevention programs. We also examined treatment indications reported in studies and eligibility criteria to confirm patients who were eligible for treatment. To compute the pooled proportions for medication prescription and initiation, we carried out a single group proportional meta-analysis. We also extracted the proportions of patients who received a prescription and/or began treatment based on age, sex, race, education, socioeconomic status, location, and chronic conditions. RESULTS: This review included 122 studies covering 114 programs. The pooled prescription rate was 77%, and the estimated medication initiation rate was 71%. Subgroup analysis revealed no significant difference in treatment initiation between the Fracture Liaison Service and other programs. Across all studies, age, sex, and socioeconomic status were the only equity variables reported in relation to treatment outcomes. CONCLUSION: Our systematic review emphasizes the need for standardized reporting guidelines in post-fracture interventions. Moreover, considering equity stratifiers in the analysis of health outcomes will help address inequities and improve the overall quality and reach of secondary fracture prevention programs.

Understanding the impact of a residential housing program for people living with HIV/AIDS: results from a realist evaluation.

BACKGROUND: In Canada, the Public Health Agency surveillance of new HIV cases has demonstrated annual increasing rates since 2020. The rates of new HIV cases are highest in the province of Saskatchewan. OBJECTIVES: The aim of the project was to conduct a resident-oriented realist evaluation of an innovative supportive housing programme, Sanctum, for people living with HIV/AIDS who also face social care issues, such as homelessness. This project took place in Saskatchewan, a province that is seeking innovative approaches to improve quality of life and HIV/AIDS management for its citizens. Our evaluation addressed how and why participants were successful (or not) within the Sanctum programme. DESIGN AND SETTING: Sanctum is a housing programme located in an inner-city location within the province of Saskatchewan. A unique component of this evaluation was the inclusion of an individual with lived experience, a resident partner, as a member of the research team. PARTICIPANTS: 11 recent Sanctum graduates, seven men and four women, were recruited for client partner-led in-depth, semistructured interviews. INTERVENTIONS: Prior to the evaluation, we developed a realist programme theory with potential causal explanations, known as context-mechanism-outcomes (CMO) configurations. Interview data from the evaluation and ongoing discussions with Sanctum board members and our resident partner were used to test, refine and validate the final programme theory and CMO configurations. RESULTS: CMO configurations at the micro (individual), meso (interpersonal) and macro (community) levels complement the over-arching programme theory. Key findings were the importance of Sanctum's harm reduction philosophy, accompanied by a non-judgmental and patient-oriented approach. Participants were supported to reduce risky behaviour, improve self-care management and develop healthier relationships within a 'safe' home-like setting. Underlying mechanisms that contributed to participants' success in the programme included: intrinsic motivation, self-worth, belongingness, empowerment and self-efficacy. Evidence-informed recommendations are offered to support Sanctum-like programme development for individuals with holistic health needs related to HIV/AIDS diagnoses and lack of access to necessary social determinants of health. CONCLUSIONS: Stigma associated with HIV/AIDS and living circumstances, such as homelessness, were successfully addressed using harm reduction principles and judgement-free approaches within a family-like environment.

Adult Phenotype of SYNGAP1-DEE.

Background and Objectives: SYNGAP1 variants are associated with rare developmental and epileptic encephalopathies (DEEs). Although SYNGAP1-related childhood phenotypes are well characterized, the adult phenotype remains ill-defined. We sought to investigate phenotypes and outcomes in adults with SYNGAP1 variants and epilepsy. Methods: Patients 18 years or older with DEE carrying likely pathogenic and pathogenic (LP/P) SYNGAP1 variants were recruited through physicians' practices and patient organization groups. We used standardized questionnaires to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder and adaptive skills of patients. We also assessed caregiver burden. Results: Fourteen unrelated adult patients (median: 21 years, range: 18-65 years) with SYNGAP1-DEE were identified, 11 with novel and 3 with known LP/P SYNGAP1 de novo variants. One patient with a partial exon 3 deletion had greater daily living skills and social skills than others with single-nucleotide variants. Ten of 14 (71%) patients had drug-resistant seizures, treated with a median of 2 antiseizure medications. All patients (100%) had abnormal pain processing. Sleep disturbances, social communication disorders, and aggressive/self-injurious behaviors were each reported in 86% of patients. Only half of adults could walk with minimal or no assistance. Toileting was normal in 29%, and 71% had constipation. No adult patients could read or understand verbal material at a sixth-grade level or higher. Aggressive/self-injurious behaviors were leading cause of caregiver burden. The oldest patient was aged 65 years; although nonambulant, she had walked independently when younger. Discussion: Seventy-one percent of patients with SYNGAP1-DEEs continue to have seizures when adults. Nonseizure comorbidities, especially aggression and self-injurious behaviors, are major management challenges in adults with SYNGAP1-DEE. Only 50% of adults can ambulate with minimal or no assistance. Almost all adult patients depend on caregivers for many activities of daily living. Prompt diagnostic genetic testing of adults with DEE can inform clinical care and guide outcomes of precision therapies.

Developing a rapid evidence response to COVID-19: The collaborative approach of Saskatchewan, Canada.

Introduction: The COVID-19 Evidence Support Team (CEST) was a provincial initiative that combined the support of policymakers, researchers, and clinical practitioners to initiate a new learning health cycle (LHS) in response to the pandemic. The primary aim of CEST was to produce and sustain the best available COVID-19 evidence to facilitate decision-making in Saskatchewan, Canada. To achieve this objective, four provincial organizations partnered to establish a single, data-driven system. Methods: The CEST partnership was driven by COVID-19 questions from Emergency Operational Committee (EOC) of the Saskatchewan Health Authority. CEST included three processes: (a) clarifying the nature and priority of COVID-19 policy and clinical questions; (b) providing Rapid Reviews (RRR) and Evidence Search Reports (ESR); and (c) seeking the requestors' evaluation of the product. A web-based repository, including a dashboard and database, was designed to house ESRs and RRRs and offered a common platform for clinicians, academics, leaders, and policymakers to find COVID-19 evidence. Results: In CEST's first year, 114 clinical and policy questions have been posed resulting in 135 ESRs and 108 RRRs. While most questions (41.3%) originated with the EOC, several other teams were assembled to address a myriad of questions related to areas such as long-term care, public health and prevention, infectious diseases, personal protective equipment, vulnerable populations, and Indigenous health. Initial challenges were mobilization of diverse partners and teams, remote work, lack of public access, and quality of emerging COVID-19 literature. Current challenges indicate the need for institutional commitment for CEST sustainability. Despite these challenges, the CEST provided the Saskatchewan LHS with a template for successful collaboration. Conclusions: The urgency of COVID-19 pandemic and the implementation of the CEST served to catalyze collaboration between different levels of a Saskatchewan LHS.

Service providers' perceptions of support needs for Indigenous cancer patients in Saskatchewan: a needs assessment.

BACKGROUND: In Saskatchewan, Canada, Indigenous cancer care services at the municipal, provincial, and federal levels are intended to improve quality care but can result in a complex, fragmented, and multi-jurisdictional health care system. A multi-phase needs assessment project was initiated to document Indigenous cancer care needs. Guided by Indigenous patient partners, clinicians, academics, and policy makers, the present study reflects a needs assessment of Indigenous cancer supports from the perspectives of cancer care service providers. METHODS: Qualitative data were collected through three focus groups with 20 service providers for cancer patients and their families at three Saskatchewan cities. Participants included chemotherapy and radiation nurses, social workers, a patient navigator, dieticians, and practicum students. A semi-structured interview guide was used to conduct the sessions to allow for freedom of responses. Data were recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Service providers' perspectives were categorized into five themes: 1) addressing travel-related issues, 2) logistical challenges, 3) improvements to Indigenous-specific health care supports, 4) cultural sensitivity in health care, and 5) consistency in care. Supports provided differed for the two Indigenous groups, First Nations and Métis. Service providers made recommendations regarding how needs could be met. They saw language translation providers and Elder supports as important. Recommendations for improving travel were for medical taxis to include breaks so that passengers may alleviate any uncomfortable side effects of their cancer treatment. Further, Indigenous-specific accommodations were recommended for those requiring medical travel. These recommendations aligned with supports that are available in four other Canadian provinces. CONCLUSIONS: These results identified gaps in supports and outlined recommendations to address barriers to cancer care from the perspectives of service providers. These recommendations may inform evidence-based health system interventions for Indigenous cancer patients and ultimately aim to improve cancer care services, quality of life, and health outcomes of Indigenous patients throughout their cancer journey.

Understanding the impact of a residential housing programme for people living with HIV/AIDS: a realist evaluation protocol.

INTRODUCTION: Housing instability and homelessness are significant barriers to medical treatment for people living with HIV/AIDS. For these individuals, lack of stable housing and stigma is associated with insufficient access to care, poor adherence to medication and higher cost burdens to the healthcare system. This protocol reports on the efforts to evaluate Sanctum V.1.0, a hospice and transitional care home for adults with HIV/AIDS in Saskatoon, Saskatchewan, Canada. The current project was developed out of a need to identify how Sanctum V.1.0 produces varying programme outcomes to assist in endeavours to replicate the programme in other geographic locations. METHODS AND ANALYSIS: A realist evaluation will be conducted to explore how and why Sanctum V.1.0 is successful or unsuccessful, in which circumstances and for whom. Rather than explore the degree to which a programme is effective, realist evaluations seek to uncover mechanisms that explain processual links between programme inputs and outcomes. The completed first phase of the project involved the development of an initial realist programme theory. Phases 2 and 3 will consist of methods to test, refine and validate the initial theory using various data sources. ETHICS AND DISSEMINATION: Ethics approval was obtained from the institutional review board at the University of Saskatchewan on 2 July 2020. Results will be disseminated according to stakeholders' desires.

Hyperoxia-activated circulating extracellular vesicles induce lung and brain injury in neonatal rats.

Hyperoxia-induced lung injury plays a key role in the development of bronchopulmonary dysplasia (BPD), characterized by inflammatory injury and impaired lung development in preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, currently it is uncertain how lung injury contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are a heterogeneous group of cell-derived membranous structures that regulate intercellular and inter-organ communications. Gasdermin D (GSDMD) has emerged as a key executor of inflammasome-mediated cell death and inflammation. In this study, we utilized a neonatal rat model of BPD to assess if hyperoxia stimulates lung release of circulating EVs and if these EVs induce lung and brain injury. We found that hyperoxia-exposed rats had elevated numbers of plasma-derived EVs compared to rats maintained in room air. These EVs also had increased cargos of surfactant protein C, a marker of type II alveolar epithelial cells (AEC), and the active (p30) form of GSDMD. When these EVs were adoptively transferred into normal newborn rats via intravenous injection, they were taken up both by lung and brain tissues. Moreover, EVs from hyperoxic animals induced not only the pathological hallmarks of BPD, but also brain inflammatory injury in recipient rats, as well as inducing cell death in cultured pulmonary vascular endothelial cells and neural stem cells (NSC). Similarly, hyperoxia-exposed cultured AEC-like cells released EVs that also contained increased GSDMD-p30 and these EVs induced pyroptotic cell death in NSC. Overall, these data indicate that hyperoxia-activated circulating EVs mediate a lung to brain crosstalk resulting in brain injury and suggest a mechanism that links lung injury and neurodevelopmental impairment in BPD infants.

The experiences of Indigenous people with cancer in Saskatchewan: a patient-oriented qualitative study using a sharing circle.

BACKGROUND: Although disparities in cancer rates, later diagnoses and lower survival rates between Indigenous and non-Indigenous people have been documented, little is known about how Indigenous patients with cancer encounter the health care system. We explored perceptions and experiences of Indigenous patients with cancer and their families to understand better how 2 key concepts - trust and world view - influence cancer care decisions. METHODS: In this patient-oriented study that included participation of 2 patient partners, qualitative data were collected from Indigenous patients with cancer and their families using an Indigenous method of sharing circles. The sharing circle occurred at a culturally appropriate place, Wanuskewin Heritage Park, Saskatoon, on Sept. 22, 2017. The first patient partner started the sharing circle by sharing their cancer journey, thus engaging the Indigenous methodology of storytelling. This patient partner was involved in selecting the data collection method and recruiting participants through snowballing and social media. Trust and world view were employed as meta themes to guide our examination of the data. In keeping with Indigenous methodology, interview transcripts were analyzed using narrative analysis. The themes were reviewed and verified by a second Indigenous patient partner. RESULTS: There were 14 participants in the sharing circle. The 2 meta themes, trust and world view, comprised 8 subthemes. The meta theme trust included mistrust with diagnosis and Western treatment after cancer therapy, protection of Indigenous medicine and physician expertise with treatment recommendations. The world view meta theme included the following subthemes: best of both worlds, spiritual beliefs, required to be strong for family and importance of knowing Indigenous survivors. INTERPRETATION: This study displayed complex relations between trust and world view in the cancer journeys of Indigenous patients and their families. These findings may assist health care providers in gaining a better understanding of how trust and world view affect the decision-making of Indigenous patients regarding cancer care.

Perceptions of health professionals regarding minimally invasive tissue sampling (MITS) to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Pakistan is considered to be one of the riskiest places in the world for childbirth as measured by its high stillbirth and neonatal mortality rates. Complete diagnostic autopsy remains the gold standard to determine the cause of death (CoD); however, it is not routinely implemented due to religious objections, sociocultural beliefs, limited resources and low demand from physicians and families. Recently, minimally invasive tissue sampling (MITS) using needle biopsies of multiple tissues to obtain tissue for histological examination and organism identification with PCR has been developed and promoted to determine CoD in low-resource areas. To ensure successful implementation of MITS, it is important to understand health professionals' attitudes and perceptions related to MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH), Karachi, Pakistan. Focus group discussions (FGDs) and Key-informant interviews (KIIs) were conducted with health professionals including doctors, nurses, trainees, clinicians, bioethics experts and public health experts to explore their perceptions and views on acceptability of MITS. Data were analyzed using NVivo 10 software. RESULTS: A total of 12 interviews (FGDs = 4; KIIs = 8) were conducted. Four overarching themes were identified: (I) acceptability of MITS; (II) perceived benefits of the MITS procedure; (III) factors facilitating the implementation of MITS; and (IV) health system requirements for implementing the MITS procedure. Generally, MITS was considered as a positive development for the health system. Diagnostic accuracy and identification of less common causes of death were highlighted as two main benefits of the MITS procedure. The study highlighted a number of facilitators for the acceptability of MITS including effective counseling, building trust with parents, fast procedure time, and approaching families within a few hours of death. In addition, lack of skilled staff, poorly equipped healthcare facilities and the potential high cost to conduct MITS were identified as challenges for the implementation of MITS. CONCLUSIONS: This formative research provided a unique opportunity to explore health professionals' views and attitudes towards the MITS procedure. Such insights are crucial to ensure successful implementation and integration of a new technique into the existing health system. The research identified the factors influencing the acceptability of MITS among health professionals in Pakistan. The study also informed factors that could help facilitate the implementation of the MITS procedures in the context of Pakistan and similar settings.

Perceptions of parents and religious leaders regarding minimal invasive tissue sampling to identify the cause of death in stillbirths and neonates: results from a qualitative study.

BACKGROUND: Recently, the minimal invasive tissue sampling (MITS) procedure has been developed to support determination of the cause of death as an alternate to conventional autopsy, especially in countries where complete diagnostic autopsy is not routine. To assess the feasibility of implementation of the MITS procedure for a study to determine cause of death in premature births and stillbirths in south Asia, we explored the views and perceptions of parents and religious leaders on the acceptability of MITS. METHODS: A qualitative study was conducted at the National Institute of Child Health (NICH) hospital of Karachi, Pakistan. Focus group discussions (FGDs) were conducted with parents of newborns who visited well-baby clinics of the NICH hospital for post-natal check-ups. Key-informant interviews (KIIs) were conducted with religious leaders. Data were analyzed using NVivo 10 software. RESULTS: A total of 13 interviews (FGDs = 8; KIIs = 5) were conducted. Three overarching themes were identified: (I) acceptability of MITS; (II) concerns affecting the implementation of MITS; and (III) religious and cultural perspectives. Participants' acceptance of MITS was based on personal, religious, cultural and social beliefs. Parents widely recognized the need for this procedure in cases where the couple had experienced multiple stillbirths, neonatal deaths and miscarriages. Counseling of parents was considered vital to address emotional concerns of the parents and the family. Religious leaders indicated acceptability of the MITS procedure from a religious perspective and advised that respect for the deceased and consent of the guardians is mandatory when performing MITS. CONCLUSIONS: This qualitative study provided a unique opportunity to understand the views of parents and religious leaders towards the use of MITS. Generally, MITS appears to be an acceptable method for identifying the cause of death in neonates and stillbirths, provided that the deceased is respected and buried as soon as possible without any delays and parents are counseled appropriately. Findings from this research are essential in approaching families for consent for MITS.

Energy Efficient Resource Allocation for M2M Devices in 5G.

Resource allocation for machine-type communication (MTC) devices is one of the keys challenges in the 5G network as it affects the lifetime of battery powered devices and also the quality of service of the applications. MTC devices are battery restrained and cannot afford a lot of power consumption due to spectrum usage. In this paper, we propose a novel resource allocation algorithm termed threshold controlled access (TCA) protocol. We propose a novel technique of uplink resource allocation in which the devices make a decision of resource allocation blocks based on their battery status and related application's power profile that eventually leads to required quality of service (QoS) metric. The first phase of the TCA algorithm selects the number of carriers to be allocated to a certain device for the better lifetime of low power MTC devices. In the second phase, the efficient solution is implemented through inducing a threshold value. A certain value of the threshold is selected through a mapping based on a QoS metric. The threshold enhances the selection of subcarriers for less powered devices, such as small e-health sensors. The algorithm is simulated for the physical layer of the 5G network. Simulation results show that the proposed algorithm is less complex and achieves better performance when compared to existing solutions in the literature.

Isomerization of 5-Hydroxy-5-methylhydantoin 2'-Deoxynucleoside into α-Furanose, ß-Furanose, α-Pyranose, and ß-Pyranose Anomers.

Oxidative damage is one of the most frequent types of DNA damage resulting from biologically generated oxygen or nitrogen reactive species. Hydroxyl radicals, one electron oxidants, and various chemical oxidants, such as permanganate and ozone, react with pyrimidine bases in DNA, cytosine and thymine, to produce 5-hydroxyhydantoin derivatives. 5-Hydroxyhydantoin modifications are interesting because they undergo ring-chain tautomerism into a pair of diastereomers via an open chain carbonyl intermediate. Here, we show that purified diastereomers of N1-(2-deoxy-ß-D-erythro-pentofuranosyl)-5-hydroxy-5-methylhydantoin not only undergo isomerization into a mixture of 5R and 5S diastereomers of the hydantoin ring but also into three additional pairs of diastereomers, in which the sugar moiety transforms into α-furanose, ß-pyranose, and α-pyranose anomers. The novel 5-hydroxy-5-methylhydantoin derivatives were characterized by extensive NMR analyses. Further studies indicate that isomerization is greatly suppressed at pH 6 compared to that at higher pH. A novel mechanism of isomerization is proposed to account for the formation of nucleoside anomers at neutral pH, which involves ring-chain tautomerism of both the hydantoin and sugar moieties. Last, the isomerization of ß-furanose into the corresponding α-furanose is shown to take place in purified DNA, albeit to a slower extent than that in solution. The ability of 5-hydroxyhydantoin nucleosides to undergo isomerization may complicate the biological processing of this damage in cellular DNA.

Long-term outcomes of transplant recipients referred for angiography for suspected transplant renal artery stenosis.

Our aim was to study the long-term outcomes of all transplant recipients who underwent angiography for suspected TRAS at our institution. The patients were divided into TRAS+ve and TRAS-ve groups based upon angiographically confirmed results. TRAS was confirmed in 58.1% of 74 patients with median time of 8.9 months. Primary angioplasty alone was performed in 56% of patients with TRAS, while the remaining had PTA with stent (PTAS). There was reduction in systolic and diastolic BP (165 ± 19-136 ± 15 mmHg and 82 ± 14 mmHg to 68 ± 12 mmHg; p < 0.05) and number of antihypertensive drugs (3.5 ± 0.9-2.7 ± 1.0; p < 0.05). Overall, graft survival and patient survival from time of transplant were similar in both groups. Graft function was similar for the patients with treated TRAS+ve as compared to TRAS-ve over time. Graft survival and patient survival when compared to an age- and year of transplant-matched cohort control group were also similar. In conclusion, angiography for suspected TRAS is more likely to yield a confirmatory result early in the transplant course as compared to late. Treatment of TRAS in these patients had sustained long-term graft function. Alternative etiologies of HTN and graft dysfunction should be sought for recipients further out from transplant.

Diagnosis and management of preeclampsia in community settings in low and middle-income countries.

Hypertensive disorders of pregnancy contribute significantly to maternal mortality and morbidity. Preeclampsia belongs to the spectrum of hypertensive disorders of pregnancy and if undiagnosed and/or untreated leads to fatal consequences for both the mother and the baby. Early detection and prevention of preeclampsia is limited by uncertainty in the knowledge about its etiopathogenesis. While much work has been done in establishing clinical guidelines for management of preeclampsia in the hospital or tertiary care settings, there is considerable lack of work in the domain of evidence-based guidelines for screening, identification and management of preeclampsia at the community-level. The article reviews these issues with special considerations and to challenges faced in low and middle-income countries. There is a need to focus on low-cost screening and interventions in the community to achieve a significant impact on preventable maternal and fetal mortality in order to control the burden of preeclampsia significantly as well as investing on more research at primary care level to improve the evidence base for community-level interventions.

Screening for toxigenic Escherichia coli in stool samples of diarrhoeal patients by polymerase chain reaction.

Escherichia coli (E. coli) are normal flora of the intestines of most animals, including humans. Most strains are harmless and beneficial to host by preventing the establishment of pathogenic bacteria within the intestine. However, some E. coli strains can cause a wide variety of intestinal and extra-intestinal diseases, such as diarrhoea, urinary tract infections, septicaemia, neonatal meningitis and renal complications. Several virulence factors including toxins, adhesins, serine proteases, etc. have been reported in these highly adapted clones. The present study was designed to enumerate toxin genotype through PCR assay in local clinical isolates of E. coli. A total of 37 E. coli strains were collected from different clinical laboratories of Karachi and examined for the presence of shiga toxin 1 (stx1) and shiga toxin 2 (stx2) genes of Eenterohemorrhagic E. Coli (EHEC) and heat stable (st) and healt labile (lt) toxin genes of enterotoxigenic E. Coli (ETEC). It was observed that 16 strains out of 37 carried one or more type of toxin genes. The presence of stx1 gene was significantly higher as it was positive in 10 isolates compared to others toxins. Two in above stx1 positive strains were also carrying for stx2 gene. Six out of 37 isolates were positive for lt gene, and none of the strains are carrying st gene. Although, the study was carried out with fewer isolates, yet it demonstrated the trend of dispersion of toxin genes and findings can be used to correlate the gastro-intestinal infections and their complications in Pakistan.

Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children.

BACKGROUND: Diarrhea is a major contributor to the burden of morbidity and mortality in children; it accounts for a median of 11% of all deaths among children aged less than 5 years, amounting to approximately 0.8 million deaths per year. Currently there is a dearth of literature exploring the effectiveness of antibiotics for diarrhea due to Cholera, Shigella and cryptosporidiosis in children. METHODS: We reviewed the literature reporting the effect of antibiotics for the treatment of diarrhea due to Cholera, Shigella and Cryptosporidium in children under five years. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of the treatment with various antibiotics on mortality and rates of clinical and bacteriological/parasitological failure. The CHERG Standard Rules were applied to determine the final effect of treatment with antibiotics on diarrhea morbidity and mortality. RESULTS: For Cholera; the evidence was weak to recommend any effect on mortality. For Shigella; there was no data on mortality; either all-cause or cause specific, hence we used clinical failure rates as a proxy for Shigella deaths and propose that treatment of Shigella dysentery with antibiotics can result in a 82% reduction in diarrhea mortality due to Shigella. For cryptosporidiosis; there was data on all-cause mortality but the evidence was weak hence we used clinical failure rates as a proxy for mortality to estimate that antimicrobial treatment of diarrhea due to cryptosporidiosis can result in a 54% reduction in mortality. CONCLUSIONS: There is evidence to recommend antibiotic use for reduction of morbidity and mortality due to Cholera, Shigella and Cryptosporidium. We recommend that more clinical trials should be conducted to evaluate the efficacy and safety of first- and second- line drugs currently in use for treatment for diarrhea and dysentery in both developing and developed countries.

Vaccines for the prevention of diarrhea due to cholera, shigella, ETEC and rotavirus.

BACKGROUND: Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development. Despite advances in the understanding of diarrheal disorders and management strategies, globally nearly 750,000 children die annually as a consequence of diarrhea. METHODS: We conducted a systematic review of the efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes. The estimated effect of cholera, shigella, Enterotoxigenic Escherichia coli (ETEC) and rotavirus vaccines was determined by applying the standard Child Health Epidemiology Reference Group (CHERG) rules. RESULTS: A total of 24 papers were selected and analyzed for all the four vaccines. Based on the evidence, we propose a 74% mortality reduction in rotavirus specific mortality, 52% reduction in cholera incidence due to their respective vaccines. We did not find sufficient evidence and a suitable outcome to project mortality reductions for cholera, ETEC and shigella in children under 5 years. CONCLUSION: Vaccines for rotavirus and cholera have the potential to reduce diarrhea morbidity and mortality burden. But there is no substantial evidence of efficacy for ETEC and shigella vaccines, although several promising vaccine concepts are moving from the development and testing pipeline towards efficacy and Phase 3 trials.

Frequency of functional constipation in 3 different populations and its causative factors.

OBJECTIVE: To assess the frequency of constipation and its causative factors in 3 different populations, namely, the hospitalized patients admitted at Civil Hospital Karachi, their attendants and medical students. METHOD: A sample size of 200 was divided into 3 groups: hospitalized patients, their attendants and medical students. Frequency of constipation was expected to be greater in patients, so 100 subjects were taken from this population; while from the other 2 populations only 50 subjects were taken. The subjects were diagnosed as constipated on the basis of Rome III criteria for functional constipation and their dietary habits and physical activity were also assessed. RESULTS: The frequency of functional constipation was found to be 53% in hospitalized patients, 52% in their attendants and 34% in medical students. Among the constipated individuals, 50.94% of hospitalized patients, 46.15% of attendants and 29.41% of medical students took laxatives for relief of their symptoms. Constipation was most prevalent among the age group of 18 to 30 years in all the 3 populations. CONCLUSION: Constipation was fairly common in all 3 populations. Male to female ratio is almost equal. Physical inactivity and low fiber intake were prominent risk factors for constipation.

Primary non-hodgkin's lymphoma of bone: experience of a decade.

OBJECTIVE: To study the prevalence and characterization of primary non Hodgkin's lymphoma of bone in a major referral center of Pakistan. METHODOLOGY: All cases of primary non Hodgkin's lymphoma of bone, diagnosed at a referral center in Pakistan from January 1998 to July 2008 have been included. Patients with diagnosis of lymphoma at some other site prior to diagnosis in bone biopsy were excluded from the study. RESULTS: Sixty cases of primary non Hodgkin's lymphoma of bone were received, with a male to female ratio of 7: 3 (42 males and 18 females). Overall, 52/60 (86.6 %) patients were diagnosed with Diffuse large B-cell non-Hodgkin's lymphoma. The largest fraction of patients was found in the pediatric group i.e. 33/60(55%) followed by elderly group i.e.15/60 (15%) and adults i.e. 12/60 (20%). The commonest sites of involvement were femur (28.3 %), hip bone (16.6%) and humerus (10%). CONCLUSION: Diffuse large B-cell lymphoma is the commonest type of primary non Hodgkin's lymphoma of bone in the Pakistani population. It is common in all ages. The sites most often involved are femur followed by hip bone. Primary non Hodgkin's lymphoma of bone appears to be more common in males. Our results are comparable to international data with various studies also showing that diffuse large B cell non Hodgkin lymphoma is the commonest primary bone lymphoma. However, primary Bone Lymphoma is more common in children and young adults.