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1.  Pelvic inflammatory disease 
BMJ Clinical Evidence  2013;2013:1606.
Introduction
Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in England and Wales.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up to date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 13 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, different durations, different regimens) and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).
Key Points
Pelvic inflammatory disease (PID) is caused by infection of the upper female genital tract, and is often asymptomatic. PID is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in 1.1% of women aged 16 to 45 years consulting their GP in England and Wales.Epithelial damage from infections such as Chlamydia trachomatis or Neisseria gonorrhoeae may allow opportunistic infection from many other bacteria.About 20% of women with PID become infertile, 40% develop chronic pain, and 1% of women who conceive have an ectopic pregnancy.Spontaneous resolution of symptoms may occur in some women. Empirical treatment is started as soon as the diagnosis of PID is suspected to minimise the risk of sequelae such as tubal obstruction and infertility. The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by three days may impair fertility.The absence of infection from the lower genital tract does not exclude a diagnosis of PID.
Oral antibiotics are likely to be beneficial, and are associated with the resolution of symptoms and signs of pelvic infection, but we don't know which antibiotic regimen is best. Clinical and microbiological cure rates of 88% to 100% have been reported after oral antibiotic treatment.The risks of tubal occlusion and infertility depend on severity of infection before treatment. Clinical improvement following treatment may not necessarily translate into improved long-term fertility .
Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility in women with mild to moderate PID, with fewer adverse effects. However, we don't know the optimal duration of treatment.
Women at high risk for PID include those with prior infection with C trachomatis or N gonorrhoeae, young age at onset of sexual activity, unprotected sexual intercourse with multiple partners, and prior history of PID. Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable. We don't know whether prophylactic antibiotics before IUD insertion reduce these risks.
PMCID: PMC3859178  PMID: 24330771
2.  Pelvic inflammatory disease 
BMJ Clinical Evidence  2008;2008:1606.
Introduction
Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the USA and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment compared with treatment delayed until the results of microbiological investigations are known? How do different antimicrobial regimens compare? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, empirical treatment, treatment guided by test results, different durations, outpatient, inpatient), and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk).
Key Points
Pelvic inflammatory disease (PID) is caused by infection of the upper female genital tract, and is often asymptomatic. PID is the most common gynaecological reason for admission to hospital in the USA, and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales.Epithelial damage from infections such as Chlamydia trachomatis or Neisseria gonorrhoeae can allow opportunistic infection from many other bacteria.About 20% of women with PID become infertile, 40% develop chronic pain, and 1% of women who conceive have an ectopic pregnancy.Spontaneous resolution of symptoms may occur in some women, but early initiation of treatment is needed to prevent impairment of fertility.
As there are no reliable signs and symptoms of PID, empirical treatment is common. The positive predictive value of clinical diagnosis is 65% to 90% compared with laparoscopy, and observational studies suggest that delaying treatment by 3 days can impair fertility.The absence of infection from the lower genital tract does not exclude a diagnosis of PID.
Oral antibiotics are likely to be beneficial, and are associated with the resolution of symptoms and signs of pelvic infection, but we don't know which antibiotic regimen is best. Clinical and microbiological cure rates of 88% to 100% have been reported after oral antibiotic treatment.The risks of tubal occlusion and infertility depend on severity of infection before treatment. Clinical improvement may not necessarily translate into improved fertility.
Oral antibiotics may be as effective as parenteral antibiotics in reducing symptoms and preserving fertility, with fewer adverse effects, and outpatient treatment is as effective as inpatient treatment for uncomplicated PID. However, we don't know the optimal duration of treatment.
Risks of PID may be increased after instrumentation of the cervix, and testing for infection before such procedures is advisable, but we don't know whether prophylactic antibiotics before IUD insertion reduce these risks.
PMCID: PMC2907941  PMID: 19450319
3.  Pelvic inflammatory disease: improving awareness, prevention, and treatment 
Purpose
Pelvic inflammatory disease (PID) is a common disorder of the reproductive tract that is frequently misdiagnosed and inadequately treated. PID and its complications, such as infertility, ectopic pregnancy, and chronic pelvic pain, are preventable by screening asymptomatic patients for sexually transmitted infections (STIs) and promptly treating individuals with STIs and PID.
Recent findings
The rates of adverse outcomes in women with PID are high and disproportionately affect young minority women. There are key opportunities for prevention including improving provider adherence with national screening guidelines for STIs and PID treatment recommendations and patient medication adherence. Nearly half of all eligible women are not screened for STIs according to national quality standards, which may increase the risk of both acute and subclinical PID. Moreover, in clinical practice, providers poorly adhere to the Centers for Disease Control and Prevention recommendations for treatment of PID. Additionally, patients with PID struggle to adhere to the current management strategies in the outpatient setting.
Conclusion
Novel evidence-based clinical and public health interventions to further reduce the rates of PID and to improve outcomes for affected women are warranted. We propose potential cost-effective approaches that could be employed in real-world settings.
doi:10.2147/IDR.S91260
PMCID: PMC4998032  PMID: 27578991
pelvic inflammatory disease; treatment; disparities
4.  How well is pelvic inflammatory disease managed in general practice? A postal questionnaire survey 
Sexually Transmitted Infections  1998;74(5):361-363.
OBJECTIVE: Many patients with pelvic inflammatory disease (PID) present to their general practitioners. Chlamydia trachomatis is the organism most commonly implicated in this condition. This study aims to examine how well PID is managed in the primary care setting and highlight areas for improvement. METHODS: The study was performed by sending postal questionnaires to 180 randomly selected general practitioners in Birmingham. Given the example of a woman presenting clinically with PID, the doctors were asked questions on diagnosis and treatment. To assess factors that may influence the answers, they were also asked about their sex, year of qualification, and postgraduate training. RESULTS: 139 questionnaires (77%) were returned. 91.4% of the respondents feel confident in managing patients with PID, and only 9.3% would usually refer these patients on. However, 54.7% do not perform an endocervical swab for C trachomatis, 37.4% do not include anti-chlamydial antibiotics in their treatment regimen, and 24.5% do not advise sexual partners to be screened. Female doctors, those with higher degrees, or obstetrics and gynaecology experience were more likely to give anti-chlamydial therapy, but no factors of the respondents significantly influenced contact tracing behaviour. CONCLUSIONS: The management of a patient presenting with PID should include investigation for C trachomatis and treatment with an appropriate antibiotic. As PID is often a sexually transmitted disease, contact tracing of sexual partners should be undertaken. The study suggests that a significant proportion of general practitioners would not have offered optimal management to patients with PID. 





PMCID: PMC1758144  PMID: 10195033
5.  Recruitment of Minority Adolescents and Young Adults into Randomised Clinical Trials: Testing the Design of the Technology Enhanced Community Health Nursing (TECH-N) Pelvic Inflammatory Disease Trial 
Purpose
Pelvic inflammatory disease (PID) disproportionately affects adolescent and young adult (AYA) women and can negatively influence reproductive health trajectories. Few randomized controlled trials (RCTs) have focused on strategies to improve outpatient adherence or to reduce reproductive morbidity in this population. This paper describes the research methods and preliminary effectiveness of recruitment, retention, and intervention strategies employed in a novel RCT designed to test a technology-enhanced community-health nursing (TECH-N) intervention among urban AYA with PID.
Methods
AYA women aged 13–25 years were recruited during acute PID visits in outpatient clinics and emergency departments (ED) to participate in this IRB-approved trial. Participants completed an audio-computerized self-interview (ACASI), provided vaginal specimens, and were randomized to standard treatment or the intervention. Intervention participants received text-messaging support for 30 days and a community health nurse (CHN) interventionist performed a home visit with clinical assessment within 5 days after enrollment. All patients received a full course of medications and completed research visits at 14-days (adherence), 30 days and 90 days with by an outreach worker. STI testing performed at the 30-and 90-day visits. Exploratory analyses using descriptive statistics were conducted to examine recruitment, retention, and follow-up data to test the overall design of the intervention.
Results
In the first 48 months, 64% of 463 patients were eligible for the study and 81.2% of 293 eligible patients were recruited for the study (63.3%); 238 (81.2%) of eligible patients were enrolled. Most participants were African American (95.6%) with a mean age of 18.6 (2.3). Ninety-four percent of individuals assigned to the TECH-N intervention completed the nursing visits. All completed visits have been within the 5-day window and over 90% of patients in both arms have been retained over the 3-month follow-up period. Biological data suggests a shift in the biological milieu with the predominance of Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections.
Conclusions
Preliminary data from the TECH-N study demonstrated that urban, low-income, minority AYA with PID can effectively be recruited and retained to participate in sexual and reproductive health RCTs with sufficient investment in the design and infrastructure of the study. Community-based sexual health interventions appear to be both feasible and acceptable in this population.
PMCID: PMC5013541  PMID: 27617108
Pelvic Inflammatory Disease; Randomized Clinical Trial; Adolescents; Minority
6.  Timing of progression from Chlamydia trachomatis infection to pelvic inflammatory disease: a mathematical modelling study 
BMC Infectious Diseases  2012;12:187.
Background
Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms from the vagina and endocervix to the upper genital tract. PID can lead to infertility, ectopic pregnancy and chronic pelvic pain. The timing of development of PID after the sexually transmitted bacterial infection Chlamydia trachomatis (chlamydia) might affect the impact of screening interventions, but is currently unknown. This study investigates three hypothetical processes for the timing of progression: at the start, at the end, or throughout the duration of chlamydia infection.
Methods
We develop a compartmental model that describes the trial structure of a published randomised controlled trial (RCT) and allows each of the three processes to be examined using the same model structure. The RCT estimated the effect of a single chlamydia screening test on the cumulative incidence of PID up to one year later. The fraction of chlamydia infected women who progress to PID is obtained for each hypothetical process by the maximum likelihood method using the results of the RCT.
Results
The predicted cumulative incidence of PID cases from all causes after one year depends on the fraction of chlamydia infected women that progresses to PID and on the type of progression. Progression at a constant rate from a chlamydia infection to PID or at the end of the infection was compatible with the findings of the RCT. The corresponding estimated fraction of chlamydia infected women that develops PID is 10% (95% confidence interval 7-13%) in both processes.
Conclusions
The findings of this study suggest that clinical PID can occur throughout the course of a chlamydia infection, which will leave a window of opportunity for screening to prevent PID.
doi:10.1186/1471-2334-12-187
PMCID: PMC3505463  PMID: 22883325
Chlamydia infection; Pelvic inflammatory disease; Mathematical model; Compartmental model; Randomised controlled trials
7.  Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies 
The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing.
doi:10.1186/1476-7961-9-6
PMCID: PMC3080807  PMID: 21477322
8.  Cervicitis in Adolescents: Do Clinicians Understand Diagnosis and Treatment? 
Background
Cervicitis is widespread, but no studies have examined cervicitis in accordance with established guidelines for diagnosis and treatment. Study objectives were to describe adherence to Centers for Disease Control and Prevention guidelines for diagnosis and treatment of cervicitis within an adolescent population and to compare factors associated with adherence to guidelines in a primary care setting and the Emergency Department.
Methods
Data were collected as part of a retrospective chart review of evaluation, diagnosis, and treatment of STI in adolescent women in an outpatient setting. Participant charts were eligible for review if they were 12–21 years of age and were given an ICD-9 and chart diagnosis of cervicitis. Two primary outcome variables: meeting cervicitis guidelines and correct treatment among those meeting cervicitis guidelines (no/yes) were utilized; the study controlled for age, race, venue, past infection with chlamydia or gonorrhea.
Results
Subjects (n = 365) were examined for the primary outcome variables and 75.1% (274/365) met at least one criterion for cervicitis. Of these, 166 (60.9%: 166/274) subjects were found to meet criteria for cervicitis alone, versus subjects meeting criteria for both cervicitis and pelvic inflammatory disease (PID) (39.4%: 108/274). The majority, 89.3%, (326/365) were treated for both chlamydia and gonorrhea, but only 64.7% (211/326) were treated correctly for both infections.
Conclusions
Our findings suggest that knowledge deficits exist in diagnosis and treatment of cervicitis in adolescent patients and in differentiating between cervicitis and PID. Educational tools, simulated patient exercises, and order sets may be warranted for quality improvement to allow for improved care of this at risk sexually active population.
doi:10.1016/j.jpag.2011.06.006
PMCID: PMC4750483  PMID: 21872515
Cervicitis; Adolescents; Pelvic inflammatory disease; CDC
9.  Management of first-episode pelvic inflammatory disease in primary care: results from a large UK primary care database 
The British Journal of General Practice  2010;60(579):e395-e406.
Background
Prompt and effective treatment of pelvic inflammatory disease (PID) may help prevent long-term complications. Many PID cases are seen in primary care but it is not known how well management follows recommended guidelines.
Aim
To estimate the incidence of first-episode PID cases seen in UK general practice, describe their management, and assess its adequacy in relation to existing guidelines.
Design of study
Cohort study.
Setting
UK general practices contributing to the General Practice Research Database (GPRD).
Method
Women aged 15 to 40 years, consulting with a first episode of PID occurring between 30 June 2003 and 30 June 2008 were identified, based on the presence of a diagnostic code. The records within 28 days either side of the diagnosis date were analysed to describe management.
Results
A total of 3797 women with a first-ever coded diagnosis of PID were identified. Incidence fell during the study period from 19.3 to 8.9/10 000 person-years. Thirty-four per cent of cases had evidence of care elsewhere, while 2064 (56%) appeared to have been managed wholly within the practice. Of these 2064 women, 34% received recommended treatment including metronidazole, and 54% had had a Chlamydia trachomatis test, but only 16% received both. Management was more likely to follow guidelines in women in their 20s, and later in the study period.
Conclusion
These analyses suggest that the management of PID in UK primary care, although improving, does not follow recommended guidelines for the majority of women. Further research is needed to understand the delivery of care in general practice and the coding of such complex syndromic conditions.
doi:10.3399/bjgp10X532404
PMCID: PMC2944949  PMID: 20883614
chlamydia; electronic health records; incidence; pelvic inflammatory disease; primary health care
10.  Chlamydia (uncomplicated, genital) 
BMJ Clinical Evidence  2010;2010:1607.
Introduction
Genital chlamydia is the most commonly reported bacterial sexually transmitted infection (STI) in developed countries. In women, infection occurs most commonly between the ages of 16 and 19 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antibiotic treatment for men and non-pregnant women with uncomplicated genital chlamydial infection?What are the effects of antibiotic treatment for pregnant women with uncomplicated genital chlamydial infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: amoxicillin, ampicillin, azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, erythromycin, lymecycline, minocycline, ofloxacin, pivampicillin, rifampicin, roxithromycin, sparfloxacin, tetracycline, and trovafloxacin.
Key Points
Genital chlamydia (Chlamydia trachomatis serotypes D–K) is a sexually transmitted infection (STI) that infects the urethra in men and the endocervix or urethra (or both) in women. It is defined as uncomplicated if it has not ascended to the upper genital tract or caused sexually acquired reactive arthritis. It is the most common bacterial STI in developed countries. Over 200,000 chlamydia diagnoses were made in the UK in 2008, with 60% of cases being detected in departments of genitourinary medicine.Infection is usually asymptomatic, particularly in women. Most people infected do not present for testing or treatment. Therefore, population rates based on routine surveillance data underestimate the true disease burden. One in 14 men and one in 11 women aged under 25 years screened as part of the National Chlamydia Screening Programme in the UK tested positive for chlamydia. If untreated, chlamydial infection can ascend to the upper genital tract, causing pelvic inflammatory disease (PID), which may result in infertility, ectopic pregnancy, or chronic pelvic pain.Partner notification and treatment is an important part of effective management.Chlamydia-positive individuals are at high risk of retesting positive within 1 year. There is a growing body of opinion that repeat testing at 3 to 12 months after treatment, or sooner if there is a change of sexual partner, is likely to be beneficial for public health.
Multiple-dose regimens of tetracyclines (doxycycline or tetracycline) achieve microbiological cure in at least 95% of men and non-pregnant women with genital chlamydia. Erythromycin also seems beneficial as a multiple-dose regimen, but we don't know which regimen of erythromycin is more effective. Ciprofloxacin seems less likely to lead to microbiological cure compared with doxycycline.We don't know whether multiple-dose regimens of other antibiotics (such as other macrolides, quinolones, and penicillins) are effective, as we found few adequate studies.
A single dose of azithromycin seems as beneficial as a 7-day course of doxycycline, and produces similar rates of adverse effects. Single-dose treatments have the obvious advantage of improving adherence.Treatment cure rates of over 95% have been reported, and a test of cure is only considered necessary if non-compliance or re-exposure is suspected.
In pregnant women, multiple-dose regimens of erythromycin or amoxicillin seem effective in treating chlamydial infection. One small study has also suggested that clindamycin and multiple-dose erythromycin are equally effective at curing infection, although the size of the study makes it hard to draw definitive conclusions.
Single-dose azithromycin may be effective in treating chlamydia in pregnant women. However, it should be used only if no adequate alternative is available.
In pregnant women, no antibiotic regimen has a microbiological cure rate of over 95%, and pregnant women should be offered a test of cure no sooner than 5 weeks after treatment was initiated to ensure that the infection has cleared.
PMCID: PMC2907609  PMID: 21718568
11.  National Trends in Pelvic Inflammatory Disease among Adolescents in the Emergency Department 
Objective
In 2002 the CDC broadened the pelvic inflammatory disease (PID) diagnostic criteria to increase detection and prevent serious sequelae of untreated PID. The impact of this change on PID detection is unknown. Our objective was to estimate trends in PID diagnosis among adolescent emergency department (ED) patients before and after the revised CDC definition and identify factors associated with PID diagnoses.
Methods
We performed a retrospective repeated cross-sectional study using the National Hospital Ambulatory Medical Care Survey from 2000–2009 of ED visits by 14 to 21 year old females. National estimates of PID rates were calculated. Multivariable logistic regression analyses and tests of trends were performed.
Results
During 2000–2009, of the 77 million female adolescent ED visits, there were an estimated 704,882 (95% CI 571,807, 837,957) cases of PID. Following the revised criteria, PID diagnosis declined from 5.4 cases per 1000 U.S. adolescent females to 3.9 cases per 1000 (p=0.03). In a multivariable model, age ≥17 years (OR 2.14, 95% CI 1.25, 3.64) and Black race (OR 2.04, 95% CI 1.36, 3.07) were associated with PID diagnosis
Conclusions
Despite broadened CDC diagnostic criteria, PID diagnoses did not increase over time. This raises concern about awareness and incorporation of the new guidelines into clinical practice.
doi:10.1016/j.jadohealth.2013.03.016
PMCID: PMC3725218  PMID: 23743002
Pelvic inflammatory disease; Adolescents; Trends
12.  The clinical diagnosis of pelvic inflammatory disease – reuse of electronic medical record data from 189 patients visiting a Swedish university hospital emergency department 
BMC Women's Health  2006;6:16.
Background
The pelvic inflammatory disease (PID) diagnosis is mostly based on clinical findings. However, few studies have examined the clinical basis for the diagnostics of PID, which was the aim of this study.
Methods
A retrospective study was performed of 189 out-patients diagnosed as having PID at the obstetric and gynecological emergency department of a Swedish university hospital. Data on symptoms, signs, pelvic examination and laboratory tests were extracted from the electronic medical records in comparison with the diagnostic criteria of the PID Guideline of the US Center of Disease Control from 2002 (CDC 2002 Guidelines).
Results
Eight symptoms in varying combinations were associated with the PID diagnosis. Most of them are mentioned in the CDC 2002 Guidelines. Detected rates of C. Trachomatis (CT) and N. Gonorrhoeae (NG) were 5% and 0%, respectively, among the tested patients (CT = 52% and NG = 12%). The C-reactive protein was normal in the majority of tested patients.
Conclusion
The clinical basis for the diagnostics of PID was largely in accordance with the criteria in the CDC 2002 Guidelines. The limited number of CT tests performed is somewhat disappointing, considering the fact that effective disease prevention includes widespread CT screening. Further studies in different settings are needed in order to analyze how the testing rate for CT can be improved in clinical praxis.
doi:10.1186/1472-6874-6-16
PMCID: PMC1624808  PMID: 17054801
13.  PID1 IS A NOVEL SENSITIZER OF BRAIN TUMOR CELLS TO CHEMOTHERAPY 
Neuro-Oncology  2014;16(Suppl 3):iii26.
BACKGROUND: PID1 is a phosphotyrosine binding domain-containing protein of unknown function in cancer. We recently provided the first report of PID1 in brain tumors (and in cancer). PID1 inhibits growth and proliferation and induces cell death, apoptosis and mitochondrial depolarization in glioblastoma, medulloblastoma and ATRT cell lines. PID1 siRNA had the opposite effect on mitochondrial depolarization. PID1 mRNA level was directly correlated with survival of patients with medulloblastoma or glioma: PID1 mRNA was lowest in tumor subgroups with the poorest prognosis and highest in the more favorable prognosis groups within each diagnosis. The mechanism by which PID1 affects these tumors is currently unknown, and is the focus of studies in our laboratory. METHODS: Experiments were conducted in tissue culture in primary and established cell lines using established methods to assess mRNA, proliferation and signal transduction. RESULTS: Since lower PID1 mRNA was associated with poorer outcome in medulloblastoma and gliomas and higher PID1 was associated with improved outcome, we hypothesized that PID1 level may affect responsiveness of these brain tumors to therapy: higher responsiveness in tumors with high PID1 and resistance when it is low. Indeed, while both cisplatin (10 µg/ml) or transient PID1 overexpression increased apoptosis of glioma and medulloblastoma cell lines (indicated by increased AnnexinV, caspase-3 cleavage and mitochondrial depolarization), combining cisplatin with PID1 caused a markedly higher effect than each alone. Moreover, knockdown of PID1 by siRNA inhibited the cisplatin-induced mitochondrial membrane depolarization and apoptosis (AnnexinV and caspase-3 cleavage), suggesting that PID1 may be required for cisplatin-induced apoptosis. This supports our hypothesis that PID1 may sensitize brain tumor cells to chemotherapy. Intriguingly, PID1 mRNA increased in response to cisplatin (5 µg/ml) as well as to etoposide (5 µg/ml) and vincristine (50ng/ml), in a time- and dose-dependent manner in the brain tumor cell lines. Further, etoposide and cisplatin also increased PID1 luciferase promoter activity. Interestingly, the increase in chemotherapy-induced PID1 promoter reporter activity as well as the chemotherapy-induced increase in PID1 mRNA were both blocked by inhibitors of NFκB, consistent with presence of an NBκB recognition site in the promoter of PID1, and indicating that regulation of PID1 may be an NFκB-dependent mechanism. CONCLUSIONS: Our data suggest that PID1 mediates glioma and medulloblastoma cell response to chemotherapy in an NFκB-dependent manner. Moreover, these data also suggest that PID1 sensitizes medulloblastoma and glioma to chemotherapy, providing the initial mechanistic step to understand the correlation between higher PID1 mRNA and survival in patients. SECONDARY CATEGORY: Pediatrics.
doi:10.1093/neuonc/nou208.11
PMCID: PMC4144555
14.  Bacterial Isolates Associated With Pelvic Inflammatory Disease Among Female Patients Attending Some Hospitals in Abuja, Nigeria 
Background
Pelvic inflammatory disease refers to any infection in the female lower reproductive tract that spreads to the upper reproductive tract. The disease comprises a spectrum of inflammatory disorders of the upper female genital tract, including any combination of endometritis, salpingitis, tubo-ovarian abscess and pelvic peritonitis. PID is not a notifiable disease in most countries, so accurate statistics are not available. This situation is not in any way different here in Nigeria and more so in the Federal Capital Territory, Abuja where this research was conducted, there had never been any published report so far on PID. It therefore became pertinent that such studies be carried out to evaluate the bacterial organisms which may be associated with the disease in this part of Nigeria so that health care providers could take a better look at this affliction in women.
Materials and Methods
Endocervical swabs totalling 100 were aseptically collected from patients with confirmed Pelvic Inflammatory Disease (PID), attending some hospitals in Abuja, Nigeria for detection of bacterial pathogens based on cultural and biochemical characterisation tests. Antibiogram was also conducted on the identified bacterial isolates.
Results
Out of the 100 samples analysed, 43% yielded pure cultures of bacterial isolates, 2% yielded mixed cultures while no bacterial growths were recorded from the remaining 55% samples. Organisms encountered were Staphylococcus aureus (16%), Escherichia coli (10%), Streptococcus faecalis (8%), Pseudomonas aeruginosa (4%), Streptococcus pyogenes (3%), Klebsiella pneumoniae (3%), Proteus rettgeri (2%) and Proteus mirabilis (1%). The highest percentage occurrence of pathogenic isolates was observed in polygamous married patients (90%). The age group most affected falls within the mean age 30.5 years (68%) while the least affected group falls within the mean age 40.5 years (5%). There was a significant difference in the acquisition of PID in relation to marital status (P < 0.05). However there was no significant difference in the acquisition of the disease with respect to age (P > 0.05). Antibiogram patterns of pathogenic isolates revealed varied resistance to most of the antibiotics employed. Cefotaxime (a new generation cephalosporin antibiotic) was established in this study as the best antimicrobial agent for treatment of PID due to Gram-positive and Gram-negative bacteria isolated from the women examined.
Conclusion
In conclusion, Pelvic inflammatory disease is a major health problem in developed or developing countries of the world. PID is not a notifiable disease, as accurate statistics on disease prevalence are rarely available. There is therefore no doubt thousands of young women have salpingitis every year and their sheer number makes it an important health problem. PID hence can be said to be a very serious complication of sexually transmitted disease which should be critically and promptly handled by healthcare providers. The right type sample should be aseptically collected and be appropriately handled for laboratory investigation. Treatment of PID should be initiated as soon as the presumptive diagnosis has been made. Immediate administration of antibiotics has been effective in the long-term sequelae associated with PID, especially new generation antibiotics, such as cefotaxime as recorded in this study.
PMCID: PMC3957208  PMID: 24653811
Bacterial isolates; Pelvic inflammatory disease; Female patients
15.  Doxycycline or Ofloxacin for Outpatient Chlamydial Pelvic Inflammatory Disease? A Cost-Benefit and Cost-Effectiveness Analysis 
Objective: The current Centers for Disease Control and Prevention (CDC) guidelines include 2 drugs, doxycycline and ofloxacin, for treatment of the chlamydial component of outpatient pelvic inflammatory disease (PID). Although ofloxacin costs about $90 more than doxycycline, doxycycline is frequently associated with side effects and patient compliance with this drug is probably poor. Because clinicians have little information by which to judge the tradeoffs between price and compliance for these 2 antibiotics, we examined the impact of patient compliance in the evaluation of the costs and benefits of using each drug.
Methods: The incidence and direct costs of PID sequelae (infertility, ectopic pregnancy, and chronic pelvic pain) resulting after partially treated chlamydial PID were taken from previous estimates. For differing levels of antibiotic compliance, the probability of cure, probability of the occurrence of sequelae, and the associated cost of each were calculated. Because the relationship between partial antibiotic compliance and PID cure is unknown, we included 3 plausible relationships in our analyses. The sensitivity analysis was performed by varying key assumptions and examining the effect of each on future costs.
Results: The average probability of future PID sequelae attributable to chlamydia is slightly less than 2%, with an associated cost of $1,272. With an average compliance for doxycycline of 50%, an improvement in compliance of as little as 1.8–3.5 percentage points (51.8–53.5%), depending on the assumption used regarding partial compliance and cure, would make the use of ofloxacin less costly than doxycycline in the long run. Even with a cost difference of $90 between the 2 drugs, a 10-percentage-point increase in compliance (to 60% compliance) with the more expensive drug would save $2.63 for each $1.00 spent.
Conclusions: Since the long-term costs of PID are likely to overshadow the immediate cost of providing treatment, physicians should carefully consider the likelihood of patient compliance in selecting an antibiotic.
doi:10.1155/S106474499500024X
PMCID: PMC2364411  PMID: 18475415
16.  Adverse Adolescent Reproductive Health Outcomes After Pelvic Inflammatory Disease 
Objective
To compare longitudinal adolescent and adult reproductive outcomes after pelvic inflammatory disease (PID).
Design
Secondary analysis of longitudinal data from the Pelvic Inflammatory Disease Evaluation and Clinical Health study.
Setting
A large multicenter randomized clinical trial assessing PID treatment strategies in the United States.
Participants
Eight hundred thirty-one female patients aged 14 to 38 years with a diagnosis of PID.
Main Exposure
Adverse longitudinal outcomes were compared in adolescents (≤19 years) and adults (>19 years).
Outcome Measures
Primary outcome measures included recurrent sexually transmitted infection at 30 days, recurrent PID, chronic abdominal pain, infertility, pregnancy, and times to recurrent PID and pregnancy. Cox proportional hazards modeling was used to examine the effect of young age on times to pregnancy and recurrent PID.
Results
Adolescents were more likely than adults to have positive results of sexually transmitted infection testing at baseline and at 30 days. There were no significant group differences in chronic abdominal pain, infertility, and recurrent PID at 35 or 84 months, but adolescents were more likely to have a pregnancy at both time points. Adjusted hazard ratios (95% confidence intervals) also demonstrated that adolescents had shorter times to pregnancy (1.48 [1.18–1.87]) and recurrent pelvic inflammatory disease (1.54 [1.03–2.30]).
Conclusion
Adolescents may require a different approach to clinical care and follow-up after PID to prevent recurrent sexually transmitted infections, recurrent PID, and unwanted pregnancies.
doi:10.1001/archpediatrics.2010.256
PMCID: PMC4415857  PMID: 21199980
17.  The effectiveness of nonsteroidal anti-inflammatory agents in the treatment of pelvic inflammatory disease: a systematic review 
Systematic Reviews  2014;3:79.
Background
Pelvic inflammatory disease (PID) is the result of infection ascending through the endocervix to the uterus and fallopian tubes. Inflammation driven by infected host cells appears to be central to the development of tissue damage and associated reproductive complications. Nonsteroidal anti-inflammatory agents (NSAIDs) therefore have the potential to reduce the sequelae associated with pelvic infection.
Methods
A search of four electronic reference databases, an internet search for relevant grey literature and a review of the bibliographies of identified publications was used to identify studies evaluating NSAIDs in the management of PID. A predefined search strategy was used to identify studies that included women with PID aged over 16 and diagnosed after 1980. Randomized controlled trials, nonrandomized controlled trials, and cohort studies with comparison group data were included without language restriction. Two reviewers independently assessed the studies against agreed criteria and extracted relevant data using a standardized pro forma. A meta-analysis to calculate the relative risk associated with NSAID use was planned if appropriate.
Results
Forty-three studies were identified. After reviewing abstracts or full texts, two randomized controlled trials were found to meet the selection criteria for inclusion. The use of NSAIDs was reported to improve tubal patency, reduce pelvic adhesions and reduce suprapubic pain but the studies were of poor quality with a high risk of bias. Meta-analysis of the data was not performed.
Conclusions
Insufficient data is available to support or refute the efficacy of NSAIDs in the prevention of short or long-term complications of PID.
doi:10.1186/2046-4053-3-79
PMCID: PMC4125595  PMID: 25052765
nonsteroidal anti-inflammatory drugs; pelvic inflammatory disease; systematic review
18.  Mycoplasma genitalium: An Emerging Cause of Pelvic Inflammatory Disease 
Mycoplasma genitalium is a sexually transmitted pathogen that is increasingly identified among women with pelvic inflammatory disease (PID). Although Chlamydia trachomatis and Neisseria gonorrhoeae frequently cause PID, up to 70% of cases have an unidentified etiology. This paper summarizes evidence linking M. genitalium to PID and its long-term reproductive sequelae. Several PCR studies have demonstrated that M. genitalium is associated with PID, independent of gonococcal and chlamydial infection. Most have been cross-sectional, although one prospective investigation suggested that M. genitalium was associated with over a thirteenfold risk of endometritis. Further, a nested case-control posttermination study demonstrated a sixfold increased risk of PID among M. genitalium positive patients. Whether or not M. genitalium upper genital tract infection results in long-term reproductive morbidity is unclear, although tubal factor infertility patients have been found to have elevated M. genitalium antibodies. Several lines of evidence suggest that M. genitalium is likely resistant to many frequently used PID treatment regimens. Correspondingly, M. genitalium has been associated with treatment failure following cefoxitin and doxycycline treatment for clinically suspected PID. Collectively, strong evidence suggests that M. genitalium is associated with PID. Further study of M. genitalium upper genital tract infection diagnosis, treatment and long-term sequelae is warranted.
doi:10.1155/2011/959816
PMCID: PMC3253449  PMID: 22235165
19.  Risk factors associated with pelvic inflammatory disease 
Sexually Transmitted Infections  2006;82(6):452-457.
Objective
To investigate factors associated with pelvic inflammatory disease (PID).
Methods
A case–control study was used to investigate demographic and behavioural factors, and causative agents associated with PID.
Results
A total of 381 participants were recruited: 140 patients, and 105 and 136 controls in tubal ligation and general practice groups, respectively. When compared with a PID‐free tubal ligation control group, increased risk of PID was associated with: age <25 years; age at first sexual intercourse <20 years; non‐white ethnicity; not having had children; a self‐reported history of a sexually transmitted disease; and exposure to Chlamydia trachomatis. When compared with a general practice control group, increased risk was associated with: age <25 years; age at first sexual intercourse <15 years; lower socioeconomic status; being single; adverse pregnancy outcome; a self‐reported history of a sexually transmitted disease; and exposure to C trachomatis. Of the cases, 64% were not associated with any of the infectious agents measured in this study (idiopathic).
Conclusions
A high proportion of cases were idiopathic. PID control strategies, which currently focus on chlamydial screening, have to be reviewed so that they can prevent all cases of PID. Behavioural change is a key factor in the primary prevention of PID, and potential modifiable risk factors were associated with PID.
doi:10.1136/sti.2005.019539
PMCID: PMC2563866  PMID: 16901918
20.  Family Physician Perspectives on Primary Immunodeficiency Diseases 
Primary immunodeficiency diseases (PIDs) include over 250 diverse disorders. The current study assessed management of PID by family practice physicians. The American Academy of Allergy, Asthma, and Immunology Primary Immunodeficiency Committee and the Immune Deficiency Foundation conducted an incentivized mail survey of family practice physician members of the American Medical Association and the American Osteopathic Association in direct patient care. Responses were compared with subspecialist immunologist responses from a similar survey. Surveys were returned by 528 (of 4500 surveys mailed) family practice physicians, of whom 44% reported following ≥1 patient with PID. Selective immunoglobulin A deficiency (21%) and chronic granulomatous disease (11%) were most common and were followed by significantly more subspecialist immunologists (P < 0.05). Use of intravenously administered immunoglobulin and live viral vaccinations across PID was significantly different (P < 0.05). Few family practice physicians were aware of professional guidelines for diagnosis and management of PID (4 vs. 79% of subspecialist immunologists, P < 0.05). Family practice physicians will likely encounter patients with PID diagnoses during their career. Differences in how family practice physicians and subspecialist immunologists manage patients with PID underscore areas where improved educational and training initiatives may benefit patient care.
doi:10.3389/fmed.2016.00012
PMCID: PMC4811961  PMID: 27066486
primary immunodeficiency disease; family practice physicians; survey; diagnosis; treatment
21.  Epidemiology and Clinical Outcome of Patients Hospitalized With Pelvic Inflammatory Disease Complicated by Tubo-Ovarian Abscess 
Objective: The purpose of this retrospective study was to compare the clinical outcome and characteristics of pelvic inflammatory disease (PID) complicated by tubo-ovarian abscess (TOA) with PID without TOA.
Methods: Chart reviews were performed for all PID admissions to the University of Medicine and Dentistry of New Jersey-University Hospital, Newark, NJ, from January 1, 1992, to December 31, 1993.
Results: The incidence in this study of TOA based on sonographic evidence of a complex adnexal mass was 18%. The major differences between the patients with and without TOAs were 1) history of hospitalization for PID: 68% (13/19) vs. 29% (25/85); 2) increased erythrocyte sedimentation rate: 82 vs. 41 mm/h; 3) increased WBC count on admission: 16,200 vs. 14,700/ml; 4) failure to respond to initial antibiotic therapy; and 5) longer hospital stay: 7.8 vs. 4.4 days, respectively. Surgical intervention was required in 3 patients: 2 patients who had TOAs and 1 patient who did not have a TOA by clinical examination or by ultrasound.
Conclusions: Despite longer hospital stays and blood tests suggesting more severe disease processes, PID complicated by TOA is usually responsive to intravenous (IV) antibiotic therapy without the need for surgical intervention.
doi:10.1155/S1064744995000470
PMCID: PMC2364435  PMID: 18476036
22.  The Delivery and Quality of Sexually Transmitted Infections Treatment by Private General Practitioners in Windhoek Namibia 
Global Journal of Health Science  2012;4(5):156-171.
Introduction:
The main objective for this study was to investigate the quality of Sexually Transmitted Infections (STI) treatment and control by the private sector in Namibia.
Method:
This was a cross-sectional study employing quantitative methodology using different methods of data collection. A self-administered questionnaire exploring General Practitioners (GPs) perceptions of factors that influence the way they manage Sexually Transmitted Infections (STI) which was then concluded with the face to face interviews and the checklist that was used while doing observations in the consulting rooms
Results:
A total of 50 private general practitioners in the area of Windhoek were interviewed, 48 self-administered questionnaires plus all checklists were received back from the private general practitioners.
None of the private general practitioners interviewed had specific training in the syndromic management of the STIs. The 86% of all patients were seen by these private general practitioners on a medical aid, while 14 % pay cash for service provided.
With regard to Urethral Discharge, an average of 56.5% of GPs could treat urethral discharge correctly as per the Namibian syndromic approach guidelines. None of the GPs could demonstrate the correct treatment of genital ulcer (whether they received medical aid or not) as recommended in the syndromic approach guidelines in Namibia (GRN, 1999; 2000). Only 28% of the GPs could demonstrate the correct treatment of Pelvic Inflammatory Disease (PID) as per the syndromic management of the STIs. For patients without medical aid the drugs prescribed and their dosages for PID are correct but the frequencies are not in line with the guidelines as for patients with medical aid.
Discussion:
In general, patients presenting with STIs to the GPs in private practices are not given quality of care because not all private general practitioners have time to do investigations, counseling, give condoms and to notify the partners of those with urethral discharge, genital ulcers and PID looking for treatment.
doi:10.5539/gjhs.v4n5p156
PMCID: PMC4776997  PMID: 22980389
private general practitioner (PGP); STI treatment; treatment guidelines; Windhoek; Namibia
23.  Untangling Therapeutic Ingredients of a Personalized Intervention for Patients with Depression and Severe COPD (PID-C) 
Objective
We developed a Personalized Intervention for Depressed Patients with COPD (PID-C) focused on mobilizing the patient to participate in the care of both conditions. We showed that PID-C reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks. This study focused on untangling key therapeutic ingredients of PID-C.
Design
Randomized controlled trial
Setting
Community
Participants
138 who received the diagnoses of COPD and major depression after screening 898 consecutive admissions for acute inpatient pulmonary rehabilitation.
Intervention
9 sessions of PID-C vs. usual care over 28 weeks.
Measurements
Primary outcomes: 17-item Hamilton Depression Rating Scale, Pulmonary Functional Status and Dyspnea Questionnaire–Modified. Other measures: adherence to rehabilitation exercise (≥2 hours/week), adherence to adequate antidepressant prescriptions.
Results
Low severity of dyspnea-related disability and adherence to antidepressants predicted subsequent improvement of depression. Exercise and low depression severity predicted improvement of dyspnea-related disability.
Conclusions
PID-C led to an interacting spiral of improvement in both depression and disability in a gravely medically ill population with a 17% mortality rate over 28 weeks and an expected deterioration in disability. The inter-relationship of the course of depression and dyspnea-related disability underscores the need to target adherence to both antidepressants and COPD rehabilitation. PID-C may serve as a care management model for depressed persons suffering from medical illnesses with a deteriorating course.
doi:10.1016/j.jagp.2013.05.006
PMCID: PMC3923856  PMID: 23954038
Geriatric depression; COPD; Personalized intervention; clinical trial; dyspnea; disability
24.  Primary immunodeficiency 
Primary immunodeficiency disorder (PID) refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID), require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides a detailed overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders.
doi:10.1186/1710-1492-7-S1-S11
PMCID: PMC3245434  PMID: 22165913
25.  Pelvic Inflammatory Disease: A Family Practice Perspective 
Canadian Family Physician  1989;35:1309-1314.
Most women with symptomatic acute pelvic inflammatory disease (PID) are now managed outside of hospital by private practitioners. Clinical diagnosis of PID is often inaccurate, but can be improved by knowledge of risk factors, use of simple investigations, and referral for laparoscopy when the physician is unsure. Prompt treatment with a recommended regimen that includes at least two antibiotics, careful consideration of when to hospitalize or refer, and an awareness of the need for compliance and follow up are important attributes of good management. In contrast, asymptomatic PID, which is a common antecedent of tubal factor infertility and ectopic pregnancy, can be prevented only by screening for and appropriate treatment of sexually transmitted infections.
Images
PMCID: PMC2280404  PMID: 21248967
C-reactive protein; Chlamydia trachomatis; erythrocyte sedimentation rate; pelvic inflammatory disease; sexually transmitted disease

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